Hier finden Sie die aktuellsten Publikationen aus dem Gebiet der Nuklearmedizin in Österreich. Zusätzlich sind die Publikationen aus den Teilbereichen der PET, SPECT sowie nuklearmedizinischen Therapien unserer Kollegen in Österreich gesondert hervorgehoben.
Rezente Publikationen in Österreich
F-FDG-PET/CT imaging in diagnostic workup of pediatric precursor B-cell lymphoblastic lymphoma
Kroeze E, Padilla LA, Burkhardt B, Attarbaschi A, von Mersi H, Kebudi R, Nievelstein RAJ, Tolboom N, Hagleitner MM, Kuiper RP, Beishuizen A and Loeffen JLC
F-FDG-PET/CT imaging in diagnostic workup of pediatric precursor B-cell lymphoblastic lymphoma
Kroeze E, Padilla LA, Burkhardt B, Attarbaschi A, von Mersi H, Kebudi R, Nievelstein RAJ, Tolboom N, Hagleitner MM, Kuiper RP, Beishuizen A and Loeffen JLC
F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) imaging is currently not used in standard diagnostics for B-cell precursor lymphoblastic lymphoma (BCP-LBL), and it is unknown whether PET/CT imaging would lead to agreement between detection of lesions with the gold standard imaging methods. Therefore, we performed a retrospective cohort study in which we included 32 pediatric BCP-LBL patients and determined localizations by reviewing local imaging reports. There was a disagreement between protocol-based imaging and PET/CT in 59% of the patients, and the discrepancies mostly comprise of additional lesions detected with PET/CT, typically in lymph node and bone or the absence of bone marrow involvement with PET/CT. If PET/CT was leading in determining definite stage of disease, this would lead to a different stage and therapy branch in 31% and 28% of the patients, respectively.
Which Patients with Prostate Cancer and Lymph Node Uptake at Preoperative Prostate-specific Membrane Antigen Positron Emission Tomography/Computerized Tomography Scan Are at a Higher Risk of Prostate-specific Antigen Persistence After Radical Prostatectomy? Identifying Indicators of Systemic Disease by Integrating Clinical, Magnetic Resonance Imaging, and Functional Imaging Parameters
Mazzone E, Gandaglia G, Robesti D, Rajwa P, Gomez Rivas J, Ibáñez L, Soeterik TFW, Bianchi L, Afferi L, Kesch C, Darr C, Guo H, Zhuang J, Zattoni F, Fendler WP, Amparore D, Huebner NA, Giesen A, Joniau S, Schiavina R, Brunocilla E, Mattei A, Dal Moro F, Moreno Sierra J, Porpiglia F, Picchio M, Chiti A, van den Bergh R, Shariat SF, Montorsi F and Briganti A
Which Patients with Prostate Cancer and Lymph Node Uptake at Preoperative Prostate-specific Membrane Antigen Positron Emission Tomography/Computerized Tomography Scan Are at a Higher Risk of Prostate-specific Antigen Persistence After Radical Prostatectomy? Identifying Indicators of Systemic Disease by Integrating Clinical, Magnetic Resonance Imaging, and Functional Imaging Parameters
Mazzone E, Gandaglia G, Robesti D, Rajwa P, Gomez Rivas J, Ibáñez L, Soeterik TFW, Bianchi L, Afferi L, Kesch C, Darr C, Guo H, Zhuang J, Zattoni F, Fendler WP, Amparore D, Huebner NA, Giesen A, Joniau S, Schiavina R, Brunocilla E, Mattei A, Dal Moro F, Moreno Sierra J, Porpiglia F, Picchio M, Chiti A, van den Bergh R, Shariat SF, Montorsi F and Briganti A
The role of local therapies including radical prostatectomy (RP) in prostate cancer (PCa) patients with clinical lymphadenopathies on prostate-specific membrane antigen (PSMA) positron emission tomography/computerized tomography (PET/CT) has scarcely been explored. Limited data are available to identify men who would benefit from RP; on the contrary, those more likely to benefit already have systemic disease.
Cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) imaging in the diagnosis and follow-up of patients with acute myocarditis and chronic inflammatory cardiomyopathy : A review paper with practical recommendations on behalf of the European Society of Cardiovascular Radiology (ESCR)
Caobelli F, Cabrero JB, Galea N, Haaf P, Loewe C, Luetkens JA, Muscogiuri G and Francone M
Cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) imaging in the diagnosis and follow-up of patients with acute myocarditis and chronic inflammatory cardiomyopathy : A review paper with practical recommendations on behalf of the European Society of Cardiovascular Radiology (ESCR)
Caobelli F, Cabrero JB, Galea N, Haaf P, Loewe C, Luetkens JA, Muscogiuri G and Francone M
Advanced cardiac imaging techniques such as cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) are widely used in clinical practice in patients with acute myocarditis and chronic inflammatory cardiomyopathies (I-CMP). We aimed to provide a review article with practical recommendations from the European Society of Cardiovascular Radiology (ESCR), in order to guide physicians in the use and interpretation of CMR and PET in clinical practice both for acute myocarditis and follow-up in chronic forms of I-CMP.
Somatostatin receptor subtype expression and radiomics from DWI-MRI represent SUV of [68Ga]Ga-DOTATOC PET in patients with meningioma
Iglseder S, Iglseder A, Beliveau V, Heugenhauser J, Gizewski ER, Kerschbaumer J, Stockhammer G, Uprimny C, Virgolini I, Dudas J, Nevinny-Stickel M, Nowosielski M and Scherfler C
Somatostatin receptor subtype expression and radiomics from DWI-MRI represent SUV of [68Ga]Ga-DOTATOC PET in patients with meningioma
Iglseder S, Iglseder A, Beliveau V, Heugenhauser J, Gizewski ER, Kerschbaumer J, Stockhammer G, Uprimny C, Virgolini I, Dudas J, Nevinny-Stickel M, Nowosielski M and Scherfler C
This retrospective study aimed to analyse the correlation between somatostatin receptor subtypes (SSTR 1-5) and maximum standardized uptake value (SUV) in meningioma patients using Gallium-68 DOTA-D-Phe1-Tyr3-octreotide Positron Emission Tomography ([68Ga]Ga-DOTATOC PET). Secondly, we developed a radiomic model based on apparent diffusion coefficient (ADC) maps derived from diffusion weighted magnetic resonance images (DWI MRI) to reproduce SUV.
A phase I/II study of the safety and efficacy of [Lu]Lu-satoreotide tetraxetan in advanced somatostatin receptor-positive neuroendocrine tumours
Wild D, Grønbæk H, Navalkissoor S, Haug A, Nicolas GP, Pais B, Ansquer C, Beauregard JM, McEwan A, Lassmann M, Pennestri D, Volteau M, Lenzo NP and Hicks RJ
A phase I/II study of the safety and efficacy of [Lu]Lu-satoreotide tetraxetan in advanced somatostatin receptor-positive neuroendocrine tumours
Wild D, Grønbæk H, Navalkissoor S, Haug A, Nicolas GP, Pais B, Ansquer C, Beauregard JM, McEwan A, Lassmann M, Pennestri D, Volteau M, Lenzo NP and Hicks RJ
We present the results of an open-label, phase I/II study evaluating the safety and efficacy of the novel somatostatin receptor (SSTR) antagonist [Lu]Lu-satoreotide tetraxetan in 40 patients with previously treated, progressive neuroendocrine tumours (NETs), in which dosimetry was used to guide maximum administered activity.
Antihormonal-Treatment Status Affects Ga-PSMA-HBED-CC PET Biodistribution in Patients with Prostate Cancer
Kluge K, Haberl D, Einspieler H, Rasul S, Gutschmayer S, Kenner L, Kramer G, Grubmüller B, Shariat S, Haug A and Hacker M
Antihormonal-Treatment Status Affects Ga-PSMA-HBED-CC PET Biodistribution in Patients with Prostate Cancer
Kluge K, Haberl D, Einspieler H, Rasul S, Gutschmayer S, Kenner L, Kramer G, Grubmüller B, Shariat S, Haug A and Hacker M
Androgen deprivation therapy (ADT) is known to influence the prostate-specific membrane antigen (PSMA) expression of prostate cancer, potentially complicating the interpretation of PSMA ligand PET findings and affecting PSMA radioligand therapy. However, the impact of ADT on PSMA ligand biodistribution in nontumorous organs is not well understood. Men ( = 112) with histologically proven prostate cancer who underwent Ga-PSMA-HBED-CC (Ga-PSMA-11) PET/CT between November 2015 and July 2021 at the Medical University Vienna with known ADT status were retrospectively recruited. Fifty-six patients were on gonadotropin-releasing hormone-interfering ADT at the time of imaging (ADT group), whereas 56 patients with no history of ADT served as a control group. Physiologically PSMA-expressing organs (salivary glands, kidneys, liver, and spleen) were delineated, and their uptake was compared according to their data distributions. Multivariate regression analysis assessed the relationship between renal, hepatic, splenic, and salivary gland uptake and the explanatory variables metabolic tumor volume, glomerular filtration rate, and ADT status. ADT was associated with lower levels of PSMA uptake in the kidneys (SUV: Δ[ADT - control] = -7.89; 95% CI, -10.73 to -5.04; < 0.001), liver (SUV: Δ[ADT - control] = -2.3; 95% CI, -5.72 to -0.93; = 0.003), spleen (SUV: Δ[ADT - control] = -1.27; 95% CI, -3.61 to -0.16; = 0.033), and salivary glands (SUV: Δ[ADT - control] = -1.04; 95% CI, -2.48 to -0.13; = 0.027). In a multivariate analysis, ADT was found to be associated with lower renal (SUV: β = -7.95; 95% CI, -11.06 to -4.84; < 0.0001), hepatic (SUV: β = -7.85; 95% CI, -11.78 to -3.91; < 0.0001), splenic (SUV: β = -5.83; 95% CI, -9.95 to -1.7; = 0.006), and salivary gland (SUV: β = -1.47; 95% CI, -2.76 to -0.17; = 0.027) uptake. A higher glomerular filtration rate was associated with a higher renal SUV (β = 0.16; 95% CI, 0.05 to 0.26; = 0.0034). These findings suggest that ADT systemically modulates PSMA expression, which may have implications for treatment-optimizing and side-effect-minimizing strategies for PSMA radioligand therapies, particularly those using more potent Ac-labeled PSMA conjugates.
European Association of Nuclear Medicine Focus 5: Consensus on Molecular Imaging and Theranostics in Prostate Cancer
Oprea-Lager DE, MacLennan S, Bjartell A, Briganti A, Burger IA, de Jong I, De Santis M, Eberlein U, Emmett L, Fizazi K, Gillessen S, Herrmann K, Heskamp S, Iagaru A, Jereczek-Fossa BA, Kunikowska J, Lam M, Nanni C, O'Sullivan JM, Panebianco V, Sala E, Sathekge M, Sosnowski R, Tilki D, Tombal B, Treglia G, Tunariu N, Walz J, Yakar D, Dierckx R, Sartor O and Fanti S
European Association of Nuclear Medicine Focus 5: Consensus on Molecular Imaging and Theranostics in Prostate Cancer
Oprea-Lager DE, MacLennan S, Bjartell A, Briganti A, Burger IA, de Jong I, De Santis M, Eberlein U, Emmett L, Fizazi K, Gillessen S, Herrmann K, Heskamp S, Iagaru A, Jereczek-Fossa BA, Kunikowska J, Lam M, Nanni C, O'Sullivan JM, Panebianco V, Sala E, Sathekge M, Sosnowski R, Tilki D, Tombal B, Treglia G, Tunariu N, Walz J, Yakar D, Dierckx R, Sartor O and Fanti S
In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand therapy, integration of advanced imaging in nomogram-based decision-making, dosimetry, and development of new theranostic applications.
Reduced hematopoietic-inflammatory response and worse outcomes in patients with recurrent myocardial infarction in comparison with primary myocardial infarction
Lu Y, Meng J, Yun M, Hacker M, Li X and Zhang X
Reduced hematopoietic-inflammatory response and worse outcomes in patients with recurrent myocardial infarction in comparison with primary myocardial infarction
Lu Y, Meng J, Yun M, Hacker M, Li X and Zhang X
Recurrent myocardial infarction (RMI) portends an unfavorable outcome, which might be related to diminished hematopoietic-inflammatory activation. We aimed to investigate the hematopoietic-inflammatory activation and the outcome in categorized patients with primary myocardial infarction (PMI) versus RMI as well as chronic stable angina (CSA) by F-FDG PET.
Automated production of [Ga]Ga-DOTA-exendin-4 via fractionated radionuclide generator elution on a cassette based synthesis module
Kraihammer M, von Guggenberg E, Hörmann AA, Gabriel M and Decristoforo C
Automated production of [Ga]Ga-DOTA-exendin-4 via fractionated radionuclide generator elution on a cassette based synthesis module
Kraihammer M, von Guggenberg E, Hörmann AA, Gabriel M and Decristoforo C
PET/CT imaging of glucagon-like peptide receptor 1 has recently filled a gap in reliably diagnosing insulinoma through non-invasive means. Ga-labelled derivatives of exendin-4 show high sensitivity as well as sufficient serum stability to enable routine clinical application. Here, we provide data for automated production of [Ga][Nle,Lys(Ahx-DOTA-Ga)NH]exendin-4 ([Ga]Ga-DOTA-exendin-4) on a cassette based synthesis module (Modular-Lab PharmTracer, Eckert & Ziegler) using commercially available cassettes in combination with an approved Ge/Ga generator (GalliaPharm, Eckert & Ziegler). This setup ensured high reproducibility as well as low radiation burden for the production team. Quality control including determination of radiochemical purity was performed by RP-HPLC using a water/0.1 % TFA/acetonitrile gradient on a C18 column. A modified TLC system with ammonium acetate & methanol as mobile phase and a novel limit test for determination of polysorbate 80 content in the final formulation are also described in this study.
Theranostic in Nuclear Medicine - The paradigm of NET
Giammarile F
Theranostic in Nuclear Medicine - The paradigm of NET
Giammarile F
Theranostics is an emerging field in medicine that combines diagnostics and therapeutics into a single approach. Overall, theranostics represents a promising paradigm for personalized medicine, as it allows for targeted and precise treatment based on individual patient characteristics. In nuclear medicine, theranostics involves the use of radiopharmaceuticals that have both diagnostic and therapeutic properties. Moreover, theranostics in nuclear medicine offers several advantages over traditional cancer treatments. Unlike radiotherapy, in nuclear medicine the therapy is systemic that targets both primary tumors and metastatic lesions, offering a more comprehensive treatment approach. Additionally, nuclear medicine therapy has been shown to have fewer side effects compared to traditional chemotherapy, making it a more tolerable treatment option for patients. While theranostics in nuclear medicine is still a relatively new field, it has shown promising results in the treatment of neuroendocrine tumors (NETs). One example of a theranostic approach in nuclear medicine is the use of radiolabeled somatostatin analogs for the treatment of NETs. Somatostatin is a hormone that regulates the release of other hormones in the body. It also binds to somatostatin receptors, which are highly expressed in NETs. The first step in theranostics for NETs is the diagnosis and staging of the disease using a radiolabeled somatostatin analog and PET/CT imaging. This allows for the detection of the tumor and assessment of its size and location. Once the tumor has been identified, the same radiolabeled somatostatin analog can be used as a therapeutic agent. The radiopharmaceutical delivers radiation directly to the tumor cells, which destroys them while sparing surrounding healthy tissue. This is known as peptide receptor radionuclide therapy (PRRT). The use of theranostics in NETs also involves the identification of specific somatostatin receptor subtypes that are expressed in the tumor cells. This is important as different somatostatin analogs have varying affinities for different receptor subtypes. By selecting the appropriate radiolabeled somatostatin analog, clinicians can increase the specificity of the therapy, delivering radiation to the tumor cells while minimizing damage to healthy tissue. PRRT has been shown to be effective in treating NETs, particularly those that are resistant to other forms of treatment. It can also be used in combination with other therapies, such as chemotherapy and surgery, to improve outcomes. As research continues, it is likely that theranostics in nuclear medicine will become an increasingly important tool in the fight against cancer, particularly in the context of NETs, offering personalized, targeted treatment options that improve patient outcomes.
Teilbereich PET
F-FDG-PET/CT imaging in diagnostic workup of pediatric precursor B-cell lymphoblastic lymphoma
Kroeze E, Padilla LA, Burkhardt B, Attarbaschi A, von Mersi H, Kebudi R, Nievelstein RAJ, Tolboom N, Hagleitner MM, Kuiper RP, Beishuizen A and Loeffen JLC
F-FDG-PET/CT imaging in diagnostic workup of pediatric precursor B-cell lymphoblastic lymphoma
Kroeze E, Padilla LA, Burkhardt B, Attarbaschi A, von Mersi H, Kebudi R, Nievelstein RAJ, Tolboom N, Hagleitner MM, Kuiper RP, Beishuizen A and Loeffen JLC
F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) imaging is currently not used in standard diagnostics for B-cell precursor lymphoblastic lymphoma (BCP-LBL), and it is unknown whether PET/CT imaging would lead to agreement between detection of lesions with the gold standard imaging methods. Therefore, we performed a retrospective cohort study in which we included 32 pediatric BCP-LBL patients and determined localizations by reviewing local imaging reports. There was a disagreement between protocol-based imaging and PET/CT in 59% of the patients, and the discrepancies mostly comprise of additional lesions detected with PET/CT, typically in lymph node and bone or the absence of bone marrow involvement with PET/CT. If PET/CT was leading in determining definite stage of disease, this would lead to a different stage and therapy branch in 31% and 28% of the patients, respectively.
Novel approach using [F]FTHA-PET and de novo synthesized VLDL for assessment of FFA metabolism in a rat model of diet induced NAFLD
Ustsinau U, Ehret V, Fürnsinn C, Scherer T, Helbich TH, Hacker M, Krššák M and Philippe C
Novel approach using [F]FTHA-PET and de novo synthesized VLDL for assessment of FFA metabolism in a rat model of diet induced NAFLD
Ustsinau U, Ehret V, Fürnsinn C, Scherer T, Helbich TH, Hacker M, Krššák M and Philippe C
The worldwide prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) raises concerns about associated risk factors, such as obesity and type 2 Diabetes Mellitus, for leading causes of disability and death. Besides Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS), functional imaging with Positron Emission Tomography (PET) could contribute to a deeper understanding of the pathophysiology of NAFLD. Here we describe a novel approach using the PET tracer [F]FTHA, which is an analog of long-chain free fatty acids (FFA) and is taken up by tissues to enter mitochondria or to be incorporated into complex lipids for further export as very-low-density lipoprotein (VLDL).
Cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) imaging in the diagnosis and follow-up of patients with acute myocarditis and chronic inflammatory cardiomyopathy : A review paper with practical recommendations on behalf of the European Society of Cardiovascular Radiology (ESCR)
Caobelli F, Cabrero JB, Galea N, Haaf P, Loewe C, Luetkens JA, Muscogiuri G and Francone M
Cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) imaging in the diagnosis and follow-up of patients with acute myocarditis and chronic inflammatory cardiomyopathy : A review paper with practical recommendations on behalf of the European Society of Cardiovascular Radiology (ESCR)
Caobelli F, Cabrero JB, Galea N, Haaf P, Loewe C, Luetkens JA, Muscogiuri G and Francone M
Advanced cardiac imaging techniques such as cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) are widely used in clinical practice in patients with acute myocarditis and chronic inflammatory cardiomyopathies (I-CMP). We aimed to provide a review article with practical recommendations from the European Society of Cardiovascular Radiology (ESCR), in order to guide physicians in the use and interpretation of CMR and PET in clinical practice both for acute myocarditis and follow-up in chronic forms of I-CMP.
Which Patients with Prostate Cancer and Lymph Node Uptake at Preoperative Prostate-specific Membrane Antigen Positron Emission Tomography/Computerized Tomography Scan Are at a Higher Risk of Prostate-specific Antigen Persistence After Radical Prostatectomy? Identifying Indicators of Systemic Disease by Integrating Clinical, Magnetic Resonance Imaging, and Functional Imaging Parameters
Mazzone E, Gandaglia G, Robesti D, Rajwa P, Gomez Rivas J, Ibáñez L, Soeterik TFW, Bianchi L, Afferi L, Kesch C, Darr C, Guo H, Zhuang J, Zattoni F, Fendler WP, Amparore D, Huebner NA, Giesen A, Joniau S, Schiavina R, Brunocilla E, Mattei A, Dal Moro F, Moreno Sierra J, Porpiglia F, Picchio M, Chiti A, van den Bergh R, Shariat SF, Montorsi F and Briganti A
Which Patients with Prostate Cancer and Lymph Node Uptake at Preoperative Prostate-specific Membrane Antigen Positron Emission Tomography/Computerized Tomography Scan Are at a Higher Risk of Prostate-specific Antigen Persistence After Radical Prostatectomy? Identifying Indicators of Systemic Disease by Integrating Clinical, Magnetic Resonance Imaging, and Functional Imaging Parameters
Mazzone E, Gandaglia G, Robesti D, Rajwa P, Gomez Rivas J, Ibáñez L, Soeterik TFW, Bianchi L, Afferi L, Kesch C, Darr C, Guo H, Zhuang J, Zattoni F, Fendler WP, Amparore D, Huebner NA, Giesen A, Joniau S, Schiavina R, Brunocilla E, Mattei A, Dal Moro F, Moreno Sierra J, Porpiglia F, Picchio M, Chiti A, van den Bergh R, Shariat SF, Montorsi F and Briganti A
The role of local therapies including radical prostatectomy (RP) in prostate cancer (PCa) patients with clinical lymphadenopathies on prostate-specific membrane antigen (PSMA) positron emission tomography/computerized tomography (PET/CT) has scarcely been explored. Limited data are available to identify men who would benefit from RP; on the contrary, those more likely to benefit already have systemic disease.
Somatostatin receptor subtype expression and radiomics from DWI-MRI represent SUV of [68Ga]Ga-DOTATOC PET in patients with meningioma
Iglseder S, Iglseder A, Beliveau V, Heugenhauser J, Gizewski ER, Kerschbaumer J, Stockhammer G, Uprimny C, Virgolini I, Dudas J, Nevinny-Stickel M, Nowosielski M and Scherfler C
Somatostatin receptor subtype expression and radiomics from DWI-MRI represent SUV of [68Ga]Ga-DOTATOC PET in patients with meningioma
Iglseder S, Iglseder A, Beliveau V, Heugenhauser J, Gizewski ER, Kerschbaumer J, Stockhammer G, Uprimny C, Virgolini I, Dudas J, Nevinny-Stickel M, Nowosielski M and Scherfler C
This retrospective study aimed to analyse the correlation between somatostatin receptor subtypes (SSTR 1-5) and maximum standardized uptake value (SUV) in meningioma patients using Gallium-68 DOTA-D-Phe1-Tyr3-octreotide Positron Emission Tomography ([68Ga]Ga-DOTATOC PET). Secondly, we developed a radiomic model based on apparent diffusion coefficient (ADC) maps derived from diffusion weighted magnetic resonance images (DWI MRI) to reproduce SUV.
Antihormonal-Treatment Status Affects Ga-PSMA-HBED-CC PET Biodistribution in Patients with Prostate Cancer
Kluge K, Haberl D, Einspieler H, Rasul S, Gutschmayer S, Kenner L, Kramer G, Grubmüller B, Shariat S, Haug A and Hacker M
Antihormonal-Treatment Status Affects Ga-PSMA-HBED-CC PET Biodistribution in Patients with Prostate Cancer
Kluge K, Haberl D, Einspieler H, Rasul S, Gutschmayer S, Kenner L, Kramer G, Grubmüller B, Shariat S, Haug A and Hacker M
Androgen deprivation therapy (ADT) is known to influence the prostate-specific membrane antigen (PSMA) expression of prostate cancer, potentially complicating the interpretation of PSMA ligand PET findings and affecting PSMA radioligand therapy. However, the impact of ADT on PSMA ligand biodistribution in nontumorous organs is not well understood. Men ( = 112) with histologically proven prostate cancer who underwent Ga-PSMA-HBED-CC (Ga-PSMA-11) PET/CT between November 2015 and July 2021 at the Medical University Vienna with known ADT status were retrospectively recruited. Fifty-six patients were on gonadotropin-releasing hormone-interfering ADT at the time of imaging (ADT group), whereas 56 patients with no history of ADT served as a control group. Physiologically PSMA-expressing organs (salivary glands, kidneys, liver, and spleen) were delineated, and their uptake was compared according to their data distributions. Multivariate regression analysis assessed the relationship between renal, hepatic, splenic, and salivary gland uptake and the explanatory variables metabolic tumor volume, glomerular filtration rate, and ADT status. ADT was associated with lower levels of PSMA uptake in the kidneys (SUV: Δ[ADT - control] = -7.89; 95% CI, -10.73 to -5.04; < 0.001), liver (SUV: Δ[ADT - control] = -2.3; 95% CI, -5.72 to -0.93; = 0.003), spleen (SUV: Δ[ADT - control] = -1.27; 95% CI, -3.61 to -0.16; = 0.033), and salivary glands (SUV: Δ[ADT - control] = -1.04; 95% CI, -2.48 to -0.13; = 0.027). In a multivariate analysis, ADT was found to be associated with lower renal (SUV: β = -7.95; 95% CI, -11.06 to -4.84; < 0.0001), hepatic (SUV: β = -7.85; 95% CI, -11.78 to -3.91; < 0.0001), splenic (SUV: β = -5.83; 95% CI, -9.95 to -1.7; = 0.006), and salivary gland (SUV: β = -1.47; 95% CI, -2.76 to -0.17; = 0.027) uptake. A higher glomerular filtration rate was associated with a higher renal SUV (β = 0.16; 95% CI, 0.05 to 0.26; = 0.0034). These findings suggest that ADT systemically modulates PSMA expression, which may have implications for treatment-optimizing and side-effect-minimizing strategies for PSMA radioligand therapies, particularly those using more potent Ac-labeled PSMA conjugates.
European Association of Nuclear Medicine Focus 5: Consensus on Molecular Imaging and Theranostics in Prostate Cancer
Oprea-Lager DE, MacLennan S, Bjartell A, Briganti A, Burger IA, de Jong I, De Santis M, Eberlein U, Emmett L, Fizazi K, Gillessen S, Herrmann K, Heskamp S, Iagaru A, Jereczek-Fossa BA, Kunikowska J, Lam M, Nanni C, O'Sullivan JM, Panebianco V, Sala E, Sathekge M, Sosnowski R, Tilki D, Tombal B, Treglia G, Tunariu N, Walz J, Yakar D, Dierckx R, Sartor O and Fanti S
European Association of Nuclear Medicine Focus 5: Consensus on Molecular Imaging and Theranostics in Prostate Cancer
Oprea-Lager DE, MacLennan S, Bjartell A, Briganti A, Burger IA, de Jong I, De Santis M, Eberlein U, Emmett L, Fizazi K, Gillessen S, Herrmann K, Heskamp S, Iagaru A, Jereczek-Fossa BA, Kunikowska J, Lam M, Nanni C, O'Sullivan JM, Panebianco V, Sala E, Sathekge M, Sosnowski R, Tilki D, Tombal B, Treglia G, Tunariu N, Walz J, Yakar D, Dierckx R, Sartor O and Fanti S
In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand therapy, integration of advanced imaging in nomogram-based decision-making, dosimetry, and development of new theranostic applications.
Reduced hematopoietic-inflammatory response and worse outcomes in patients with recurrent myocardial infarction in comparison with primary myocardial infarction
Lu Y, Meng J, Yun M, Hacker M, Li X and Zhang X
Reduced hematopoietic-inflammatory response and worse outcomes in patients with recurrent myocardial infarction in comparison with primary myocardial infarction
Lu Y, Meng J, Yun M, Hacker M, Li X and Zhang X
Recurrent myocardial infarction (RMI) portends an unfavorable outcome, which might be related to diminished hematopoietic-inflammatory activation. We aimed to investigate the hematopoietic-inflammatory activation and the outcome in categorized patients with primary myocardial infarction (PMI) versus RMI as well as chronic stable angina (CSA) by F-FDG PET.
Automated production of [Ga]Ga-DOTA-exendin-4 via fractionated radionuclide generator elution on a cassette based synthesis module
Kraihammer M, von Guggenberg E, Hörmann AA, Gabriel M and Decristoforo C
Automated production of [Ga]Ga-DOTA-exendin-4 via fractionated radionuclide generator elution on a cassette based synthesis module
Kraihammer M, von Guggenberg E, Hörmann AA, Gabriel M and Decristoforo C
PET/CT imaging of glucagon-like peptide receptor 1 has recently filled a gap in reliably diagnosing insulinoma through non-invasive means. Ga-labelled derivatives of exendin-4 show high sensitivity as well as sufficient serum stability to enable routine clinical application. Here, we provide data for automated production of [Ga][Nle,Lys(Ahx-DOTA-Ga)NH]exendin-4 ([Ga]Ga-DOTA-exendin-4) on a cassette based synthesis module (Modular-Lab PharmTracer, Eckert & Ziegler) using commercially available cassettes in combination with an approved Ge/Ga generator (GalliaPharm, Eckert & Ziegler). This setup ensured high reproducibility as well as low radiation burden for the production team. Quality control including determination of radiochemical purity was performed by RP-HPLC using a water/0.1 % TFA/acetonitrile gradient on a C18 column. A modified TLC system with ammonium acetate & methanol as mobile phase and a novel limit test for determination of polysorbate 80 content in the final formulation are also described in this study.
Theranostic in Nuclear Medicine - The paradigm of NET
Giammarile F
Theranostic in Nuclear Medicine - The paradigm of NET
Giammarile F
Theranostics is an emerging field in medicine that combines diagnostics and therapeutics into a single approach. Overall, theranostics represents a promising paradigm for personalized medicine, as it allows for targeted and precise treatment based on individual patient characteristics. In nuclear medicine, theranostics involves the use of radiopharmaceuticals that have both diagnostic and therapeutic properties. Moreover, theranostics in nuclear medicine offers several advantages over traditional cancer treatments. Unlike radiotherapy, in nuclear medicine the therapy is systemic that targets both primary tumors and metastatic lesions, offering a more comprehensive treatment approach. Additionally, nuclear medicine therapy has been shown to have fewer side effects compared to traditional chemotherapy, making it a more tolerable treatment option for patients. While theranostics in nuclear medicine is still a relatively new field, it has shown promising results in the treatment of neuroendocrine tumors (NETs). One example of a theranostic approach in nuclear medicine is the use of radiolabeled somatostatin analogs for the treatment of NETs. Somatostatin is a hormone that regulates the release of other hormones in the body. It also binds to somatostatin receptors, which are highly expressed in NETs. The first step in theranostics for NETs is the diagnosis and staging of the disease using a radiolabeled somatostatin analog and PET/CT imaging. This allows for the detection of the tumor and assessment of its size and location. Once the tumor has been identified, the same radiolabeled somatostatin analog can be used as a therapeutic agent. The radiopharmaceutical delivers radiation directly to the tumor cells, which destroys them while sparing surrounding healthy tissue. This is known as peptide receptor radionuclide therapy (PRRT). The use of theranostics in NETs also involves the identification of specific somatostatin receptor subtypes that are expressed in the tumor cells. This is important as different somatostatin analogs have varying affinities for different receptor subtypes. By selecting the appropriate radiolabeled somatostatin analog, clinicians can increase the specificity of the therapy, delivering radiation to the tumor cells while minimizing damage to healthy tissue. PRRT has been shown to be effective in treating NETs, particularly those that are resistant to other forms of treatment. It can also be used in combination with other therapies, such as chemotherapy and surgery, to improve outcomes. As research continues, it is likely that theranostics in nuclear medicine will become an increasingly important tool in the fight against cancer, particularly in the context of NETs, offering personalized, targeted treatment options that improve patient outcomes.
Teilbereich SPECT
Correlation of 99mTc-DPD bone scintigraphy with histological amyloid load in patients with ATTR cardiac amyloidosis
Ungericht M, Groaz V, Messner M, Schuetz T, Brunelli L, Zaruba MM, Lener D, Stocker E, Bauer A, Kroiss AS, Mayr A, Röcken C and Poelzl G
Correlation of 99mTc-DPD bone scintigraphy with histological amyloid load in patients with ATTR cardiac amyloidosis
Ungericht M, Groaz V, Messner M, Schuetz T, Brunelli L, Zaruba MM, Lener D, Stocker E, Bauer A, Kroiss AS, Mayr A, Röcken C and Poelzl G
The significance of measuring 99mTc-labelled-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) in transthyretin (ATTR) cardiac amyloidosis has not been adequately studied. This single-centre observational study evaluated the correlation between 99mTc-DPD scintigraphy and histological amyloid load in endomyocardial biopsy (EMB).
A machine learning method integrating ECG and gated SPECT for cardiac resynchronization therapy decision support
de A Fernandes F, Larsen K, He Z, Nascimento E, Peix A, Sha Q, Paez D, Garcia EV, Zhou W and Mesquita CT
A machine learning method integrating ECG and gated SPECT for cardiac resynchronization therapy decision support
de A Fernandes F, Larsen K, He Z, Nascimento E, Peix A, Sha Q, Paez D, Garcia EV, Zhou W and Mesquita CT
Cardiac resynchronization therapy (CRT) has been established as an important therapy for heart failure. Mechanical dyssynchrony has the potential to predict responders to CRT. The aim of this study was to report the development and the validation of machine learning models which integrate ECG, gated SPECT MPI (GMPS), and clinical variables to predict patients' response to CRT.
Bone Metastasis in Prostate Cancer: Bone Scan Versus PET Imaging
Mohseninia N, Zamani-Siahkali N, Harsini S, Divband G, Pirich C and Beheshti M
Bone Metastasis in Prostate Cancer: Bone Scan Versus PET Imaging
Mohseninia N, Zamani-Siahkali N, Harsini S, Divband G, Pirich C and Beheshti M
Prostate cancer is the second most common cause of malignancy among men, with bone metastasis being a significant source of morbidity and mortality in advanced cases. Detecting and treating bone metastasis at an early stage is crucial to improve the quality of life and survival of prostate cancer patients. This objective strongly relies on imaging studies. While CT and MRI have their specific utilities, they also possess certain drawbacks. Bone scintigraphy, although cost-effective and widely available, presents high false-positive rates. The emergence of PET/CT and PET/MRI, with their ability to overcome the limitations of standard imaging methods, offers promising alternatives for the detection of bone metastasis. Various radiotracers targeting cell division activity or cancer-specific membrane proteins, as well as bone seeking agents, have been developed and tested. The use of positron-emitting isotopes such as fluorine-18 and gallium-68 for labeling allows for a reduced radiation dose and unaffected biological properties. Furthermore, the integration of artificial intelligence (AI) and radiomics techniques in medical imaging has shown significant advancements in reducing interobserver variability, improving accuracy, and saving time. This article provides an overview of the advantages and limitations of bone scan using SPECT and SPECT/CT and PET imaging methods with different radiopharmaceuticals and highlights recent developments in hybrid scanners, AI, and radiomics for the identification of prostate cancer bone metastasis using molecular imaging.
Reduction in Tc-DPD myocardial uptake with therapy of ATTR cardiomyopathy
Rettl R, Calabretta R, Duca F, Binder C, Kronberger C, Willixhofer R, Poledniczek M, Donà C, Nitsche C, Beitzke D, Loewe C, Auer-Grumbach M, Bonderman D, Kastl S, Hengstenberg C, Badr Eslam R, Kastner J, Bergler-Klein J, Hacker M and Kammerlander A
Reduction in Tc-DPD myocardial uptake with therapy of ATTR cardiomyopathy
Rettl R, Calabretta R, Duca F, Binder C, Kronberger C, Willixhofer R, Poledniczek M, Donà C, Nitsche C, Beitzke D, Loewe C, Auer-Grumbach M, Bonderman D, Kastl S, Hengstenberg C, Badr Eslam R, Kastner J, Bergler-Klein J, Hacker M and Kammerlander A
Novel ribonucleic acid interference (RNAi) therapeutics such as patisiran and inotersen have been shown to benefit neurologic disease course and quality of life in patients with hereditary transthyretin amyloidosis (ATTRv). We aimed to determine the impact of RNAi therapeutics on myocardial amyloid load using quantitative single photon emission computed tomography/computed tomography (SPECT/CT) imaging in patients with ATTRv-related cardiomyopathy (ATTRv-CM). We furthermore compared them with wild-type ATTR-CM (ATTRwt-CM) patients treated with tafamidis. ATTRv-CM patients underwent [Tc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid (Tc-DPD) scintigraphy and quantitative SPECT/CT imaging before and after 12 months (IQR: 11.0-12.0) of treatment with RNAi therapeutics (patisiran: = 5, inotersen: = 4). RNAi treatment significantly reduced quantitative myocardial uptake as measured by standardised uptake value (SUV) retention index (baseline: 5.09 g/mL vs. follow-up: 3.19 g/mL, = .028) in ATTRv-CM patients without significant improvement in cardiac function. Tafamidis treatment resulted in a significant reduction in SUV retention index (4.96 g/mL vs. 3.27 g/mL, < .001) in ATTRwt-CM patients (historical control cohort: = 40) at follow-up [9.0 months (IQR: 7.0-10.0)] without beneficial impact on cardiac function. RNAi therapeutics significantly reduce quantitative myocardial uptake in ATTRv-CM patients, comparable to tafamidis treatment in ATTRwt-CM patients, without impact on cardiac function. Serial Tc-DPD SPECT/CT imaging may be a valuable tool to quantify and monitor response to disease-specific therapies in both ATTRv-CM and ATTRwt-CM.
Monitoring tafamidis treatment with quantitative SPECT/CT in transthyretin amyloid cardiomyopathy
Rettl R, Wollenweber T, Duca F, Binder C, Cherouny B, Dachs TM, Camuz Ligios L, Schrutka L, Dalos D, Beitzke D, Loewe C, Badr Eslam R, Kastner J, Hacker M and Bonderman D
Monitoring tafamidis treatment with quantitative SPECT/CT in transthyretin amyloid cardiomyopathy
Rettl R, Wollenweber T, Duca F, Binder C, Cherouny B, Dachs TM, Camuz Ligios L, Schrutka L, Dalos D, Beitzke D, Loewe C, Badr Eslam R, Kastner J, Hacker M and Bonderman D
Tafamidis treatment positively affects left ventricular (LV) structure and function and improves outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). We aimed to investigate the relationship between treatment response and cardiac amyloid burden identified by serial quantitative 99mTc-DPD SPECT/CT. We furthermore aimed to identify nuclear imaging biomarkers that could be used to quantify and monitor response to tafamidis therapy.
SPECT and PET myocardial perfusion imaging in Austria, Germany, and Switzerland results of the first joint survey of 2021
Lindner O, Hacker M, Burchert W and Buechel RR
SPECT and PET myocardial perfusion imaging in Austria, Germany, and Switzerland results of the first joint survey of 2021
Lindner O, Hacker M, Burchert W and Buechel RR
This paper presents the results of the first joint survey on the use of SPECT and PET myocardial perfusion imaging (MPI) and cardiac amyloidosis imaging in Austria, Germany, and Switzerland of the year 2021.
Development of the Tc-Labelled SST Antagonist TECANT-1 for a First-in-Man Multicentre Clinical Study
Novak D, Janota B, Hörmann AA, Sawicka A, Kroselj M, Hubalewska-Dydejczyk A, Fani M, Mikolajczak R, Kolenc P, Decristoforo C and Garnuszek P
Development of the Tc-Labelled SST Antagonist TECANT-1 for a First-in-Man Multicentre Clinical Study
Novak D, Janota B, Hörmann AA, Sawicka A, Kroselj M, Hubalewska-Dydejczyk A, Fani M, Mikolajczak R, Kolenc P, Decristoforo C and Garnuszek P
Broad availability and cost-effectiveness of Mo/Tc generators worldwide support the use, and thus the development, of novel Tc-labelled radiopharmaceuticals. In recent years, preclinical and clinical developments for neuroendocrine neoplasms patient management focused on somatostatin receptor subtype 2 (SST) antagonists, mainly due to their superiority in SST-tumour targeting and improved diagnostic sensitivity over agonists. The goal of this work was to provide a reliable method for facile preparation of a Tc-labelled SST antagonist, [Tc]Tc-TECANT-1, in a hospital radiopharmacy setting, suitable for a multi-centre clinical trial. To ensure successful and reproducible on-site preparation of the radiopharmaceutical for human use shortly before administration, a freeze-dried three-vial kit was developed. The final composition of the kit was established based on the radiolabelling results obtained during the optimisation process, in which variables such as precursor content, pH and buffer, as well as kit formulations, were tested. Finally, the prepared GMP-grade batches met all predefined specification parameters together with long-term kit stability and stability of the product [Tc]Tc-TECANT-1. Furthermore, the selected precursor content complies with micro-dosing, based on an extended single-dose toxicity study, where histopathology NOEL was established at 0.5 mg/kg BW, being more than 1000 times higher than the planned human dose of 20 µg. In conclusion, [Tc]Tc-TECANT-1 is suitable to be advanced into a first-in-human clinical trial.
Molecular Imaging Diagnosis of Renal Cancer Using Tc-Sestamibi SPECT/CT and Girentuximab PET-CT-Current Evidence and Future Development of Novel Techniques
Tataru OS, Marchioni M, Crocetto F, Barone B, Lucarelli G, Del Giudice F, Busetto GM, Veccia A, Lo Giudice A, Russo GI, Luzzago S, Piccinelli ML, Vartolomei MD, Musi G and Ferro M
Molecular Imaging Diagnosis of Renal Cancer Using Tc-Sestamibi SPECT/CT and Girentuximab PET-CT-Current Evidence and Future Development of Novel Techniques
Tataru OS, Marchioni M, Crocetto F, Barone B, Lucarelli G, Del Giudice F, Busetto GM, Veccia A, Lo Giudice A, Russo GI, Luzzago S, Piccinelli ML, Vartolomei MD, Musi G and Ferro M
Novel molecular imaging opportunities to preoperatively diagnose renal cell carcinoma is under development and will add more value in limiting the postoperative renal function loss and morbidity. We aimed to comprehensively review the research on single photon emission computed tomography/computed tomography (SPECT/CT) and positron emission tomography computed tomography (PET-CT) molecular imaging and to enhance the urologists' and radiologists' knowledge of the current research pattern. We identified an increase in prospective and also retrospective studies that researched to distinguish between benign and malignant lesions and between different clear cell renal cell carcinoma subtypes, with small numbers of patients studied, nonetheless with excellent results on specificity, sensitivity and accuracy, especially for Tc-sestamibi SPECT/CT that delivers quick results compared to a long acquisition time for girentuximab PET-CT, which instead gives better image quality. Nuclear medicine has helped clinicians in evaluating primary and secondary lesions, and has lately returned with new and exciting insights with novel radiotracers to reinforce its diagnostic potential in renal carcinoma. To further limit the renal function loss and post-surgery morbidity, future research is mandatory to validate the results and to clinically implement the diagnostic techniques in the context of precision medicine.
The effect of percutaneous tract dilation technique on renal parenchymal trauma: An experimental study on a porcine model
Tsaturyan A, Adamou C, Pantazis L, Kalogeropoulou C, Tzelepi V, Apostolopoulos D, Pagonis K, Peteinaris A, Natsos A, Vrettos T, Al-Aown A, Liatsikos E and Kallidonis P
The effect of percutaneous tract dilation technique on renal parenchymal trauma: An experimental study on a porcine model
Tsaturyan A, Adamou C, Pantazis L, Kalogeropoulou C, Tzelepi V, Apostolopoulos D, Pagonis K, Peteinaris A, Natsos A, Vrettos T, Al-Aown A, Liatsikos E and Kallidonis P
The purpose of this study was to evaluate renal parenchymal trauma of two-step dilation compared to the conventional Amplatz gradual dilation during percutaneous nephrolithotomy on a porcine model.
Case report: Myocardial perfusion gated-SPECT in pulmonary artery hypertension-the Movahed's sign
Hamzaraj K, Angjeliu S, Knopf P, Stadler M, Zbucki K, Kastrati L, Graf S, Gyöngyösi M, Hacker M and Calabretta R
Case report: Myocardial perfusion gated-SPECT in pulmonary artery hypertension-the Movahed's sign
Hamzaraj K, Angjeliu S, Knopf P, Stadler M, Zbucki K, Kastrati L, Graf S, Gyöngyösi M, Hacker M and Calabretta R
Primary pulmonary artery hypertension (PAH) is a clinical diagnosis that requires the exclusion of other underlying causes of pulmonary hypertension (PH). Increased pulmonary artery (PA) pressure and subsequent right ventricular (RV) pressure overload often result in a flattening of the curved interventricular septum, leading to a D-shaped left ventricle (LV), as observed in echocardiographic short-axis views. A similar finding may be also observed on myocardial perfusion SPECT images, the so-called Movahed's sign. We present a clinical case of a female patient with PAH and progression of exertional dyspnea that underwent myocardial perfusion SPECT to investigate LV myocardial ischemia. The SPECT images revealed enhanced tracer uptake in the dilated right ventricle. Additionally, we observed a D-shaped LV or Movahed's sign, which may serve as a potential marker of RV pressure overload, along with a small stress-induced perfusion defect on the LV septal wall. Our findings highlight the importance of considering the presence of a D-shaped LV and signs of RV pressure overload, as they can alter the interpretation of LV perfusion deficits on SPECT images. This case report aims to emphasize the complex nature of right heart abnormalities in pathologies such as PAH and the consideration of the RV implications in myocardial SPECT images-which typically focus solely on the LV.
Teilbereich Nuklearmedizinische Therapie
A phase I/II study of the safety and efficacy of [Lu]Lu-satoreotide tetraxetan in advanced somatostatin receptor-positive neuroendocrine tumours
Wild D, Grønbæk H, Navalkissoor S, Haug A, Nicolas GP, Pais B, Ansquer C, Beauregard JM, McEwan A, Lassmann M, Pennestri D, Volteau M, Lenzo NP and Hicks RJ
A phase I/II study of the safety and efficacy of [Lu]Lu-satoreotide tetraxetan in advanced somatostatin receptor-positive neuroendocrine tumours
Wild D, Grønbæk H, Navalkissoor S, Haug A, Nicolas GP, Pais B, Ansquer C, Beauregard JM, McEwan A, Lassmann M, Pennestri D, Volteau M, Lenzo NP and Hicks RJ
We present the results of an open-label, phase I/II study evaluating the safety and efficacy of the novel somatostatin receptor (SSTR) antagonist [Lu]Lu-satoreotide tetraxetan in 40 patients with previously treated, progressive neuroendocrine tumours (NETs), in which dosimetry was used to guide maximum administered activity.
Novel Discovery of the Somatostatin Receptor (SSTR2) in Pleomorphic Adenomas via Immunohistochemical Analysis of Tumors of the Salivary Glands
Johnson F, Hofauer B, Wirth M, Wollenberg B, Stögbauer F, Notohamiprodjo S, Haller B, Reschke R, Knopf A and Strassen U
Novel Discovery of the Somatostatin Receptor (SSTR2) in Pleomorphic Adenomas via Immunohistochemical Analysis of Tumors of the Salivary Glands
Johnson F, Hofauer B, Wirth M, Wollenberg B, Stögbauer F, Notohamiprodjo S, Haller B, Reschke R, Knopf A and Strassen U
Reliable preoperative diagnosis between salivary gland tumor entities is difficult. In this monocentric retrospective study, we examined the somatostatin receptor 2 (SSTR2) status of salivary gland tumors after salivary gland tumor resection via immunohistochemistry (IHC), and stains were compared in analogy to the HER2 mamma scale. A total of 42.3% of all pleomorphic adenoma (PA) tumors (42 of 99, 95% confidence interval 32.5-52.8%) demonstrated ≥20% of cells displaying the SSTR2 as compared to just 1% of all other tumors (1/160, 95% CI 0.02-3.4%). The other tumor was a neuroendocrine carcinoma. PA had a higher intensity of SSTR2 staining, with 90.9% staining ≥ an intensity of 2 (moderate). Tumors with an intensity of SSTR2 expression equal to or greater than 2 had an 89.9% likelihood of being a PA (95% CI: 82.2-95.0%, AUC: 0.928). Only one Warthin tumor demonstrated a 'strong' SSTR2 staining intensity. No Warthin tumor showed a percentage of cells staining for SSTR2 above ≥20%. This result demonstrates consistent and strong expression of SSTR2 in PAs as compared to Warthin tumors, which may allow physicians to utilize radioligand-somatostatin analog PET CT/MR imaging to diagnose the PA. SSTR2 positivity, if shown to be clinically relevant, may allow peptide receptor radionuclide therapy in the future.
Automated Synthesis of [Ga]Ga-FAPI-46 on a Scintomics GRP Synthesizer
Plhak E, Pichler C, Dittmann-Schnabel B, Gößnitzer E, Aigner RM, Stanzel S and Kvaternik H
Automated Synthesis of [Ga]Ga-FAPI-46 on a Scintomics GRP Synthesizer
Plhak E, Pichler C, Dittmann-Schnabel B, Gößnitzer E, Aigner RM, Stanzel S and Kvaternik H
[Ga]Ga-FAPI-46 is a radiolabelled fibroblast activation protein inhibitor that selectively binds to fibroblast activation protein (FAP), which is overexpressed by cancer-associated fibroblasts (CAFs) in the tumour microenvironment. In recent years, radiolabelled FAP inhibitors (FAPIs) are becoming increasingly important in cancer diagnostics and also for targeted radionuclide therapy. Because of the increasing demand for radiolabelled FAPIs, automating the synthesis of these compounds is of great interest. In this work, we present a newly programmed automatic synthesis process of [Ga]Ga-FAPI-46 on a Scintomics GRP module using two Galli Ad generators as a radionuclide source. Dedicated cassettes for the labelling of Ga-peptides were used without any modifications. The generators were connected via a three-way valve to the module and eluted automatically over a strong cation exchange (SCX) cartridge by using the vacuum pump of the synthesis module, eliminating the need to transfer the eluates into a separate vial. After a reaction step in HEPES buffer, the compound was purified by solid-phase extraction (SPE) over a Sep-Pak Light C18 cartridge. The evaluation of 10 routine syntheses of [Ga]Ga-FAPI-46 resulted in a radiochemical yield of 72.6 ± 4.9%. The radiochemical purity was 97.6 ± 0.3%, and the amount of free gallium-68 and colloid was <2%. The final product fulfilled the quality criteria, which were adapted from relevant monographs of the (Ph. Eur.). This work presents the successful preparation of multiple doses of [Ga]Ga-FAPI-46 in a GMP-compliant automated process for clinical use.
A cycle-consistent adversarial network for brain PET partial volume correction without prior anatomical information
Sanaat A, Shooli H, Böhringer AS, Sadeghi M, Shiri I, Salimi Y, Ginovart N, Garibotto V, Arabi H and Zaidi H
A cycle-consistent adversarial network for brain PET partial volume correction without prior anatomical information
Sanaat A, Shooli H, Böhringer AS, Sadeghi M, Shiri I, Salimi Y, Ginovart N, Garibotto V, Arabi H and Zaidi H
Partial volume effect (PVE) is a consequence of the limited spatial resolution of PET scanners. PVE can cause the intensity values of a particular voxel to be underestimated or overestimated due to the effect of surrounding tracer uptake. We propose a novel partial volume correction (PVC) technique to overcome the adverse effects of PVE on PET images.
Improved quality control of [Lu]Lu-PSMA I&T
Kraihammer M, Garnuszek P, Bauman A, Maurin M, Alejandre Lafont M, Haubner R, von Guggenberg E, Gabriel M and Decristoforo C
Improved quality control of [Lu]Lu-PSMA I&T
Kraihammer M, Garnuszek P, Bauman A, Maurin M, Alejandre Lafont M, Haubner R, von Guggenberg E, Gabriel M and Decristoforo C
Targeted radionuclide therapy with [Lu]Lu-PSMA I&T (zadavotide guraxetan) has proven high efficacy and safety in treating patients with advanced prostate cancer worldwide. Several methods to determine the radiochemical purity have been reported but also limitations in the HPLC analysis due to retention of the sample and tailing effects when using standard gradients containing trifluoroacetic acid (TFA). We here report on the validation of a method for quality control of [Lu]Lu-PSMA I&T including determination of radiochemical purity, identity testing and limit test for PSMA I&T by HPLC using a Phosphate buffer /Acetonitrile gradient system, complemented with a TLC system with 0.1N Citrate buffer pH 5 as mobile phase including validation of the methods, batch and stability data as well as identification of the main radiochemical impurity by mass spectrometry.
Effect of -Terminal Peptide Modifications on In Vitro and In Vivo Properties of Lu-Labeled Peptide Analogs Targeting CCK2R
Hörmann AA, Klingler M, Rangger C, Mair C, Joosten L, Franssen GM, Laverman P and von Guggenberg E
Effect of -Terminal Peptide Modifications on In Vitro and In Vivo Properties of Lu-Labeled Peptide Analogs Targeting CCK2R
Hörmann AA, Klingler M, Rangger C, Mair C, Joosten L, Franssen GM, Laverman P and von Guggenberg E
The therapeutic potential of minigastrin (MG) analogs for the treatment of cholecystokinin-2 receptor (CCK2R)-expressing cancers is limited by poor in vivo stability or unfavorable accumulation in non-target tissues. Increased stability against metabolic degradation was achieved by modifying the C-terminal receptor-specific region. This modification led to significantly improved tumor targeting properties. In this study, further -terminal peptide modifications were investigated. Two novel MG analogs were designed starting from the amino acid sequence of DOTA-MGS5 (DOTA-DGlu-Ala-Tyr-Gly-Trp-(-Me)Nle-Asp-1Nal-NH). Introduction of a penta-DGlu moiety and replacement of the four -terminal amino acids by a non-charged hydrophilic linker was investigated. Retained receptor binding was confirmed using two CCK2R-expressing cell lines. The effect on metabolic degradation of the new Lu-labeled peptides was studied in human serum in vitro, as well as in BALB/c mice in vivo. The tumor targeting properties of the radiolabeled peptides were assessed using BALB/c nude mice bearing receptor-positive and receptor-negative tumor xenografts. Both novel MG analogs were found to have strong receptor binding, enhanced stability, and high tumor uptake. Replacement of the four -terminal amino acids by a non-charged hydrophilic linker lowered the absorption in the dose-limiting organs, whereas introduction of the penta-DGlu moiety increased uptake in renal tissue.
Effects of Side Chain and Peptide Bond Modifications on the Targeting Properties of Stabilized Minigastrin Analogs
Zavvar TS, Hörmann AA, Klingler M, Summer D, Rangger C, Desrues L, Castel H, Gandolfo P and von Guggenberg E
Effects of Side Chain and Peptide Bond Modifications on the Targeting Properties of Stabilized Minigastrin Analogs
Zavvar TS, Hörmann AA, Klingler M, Summer D, Rangger C, Desrues L, Castel H, Gandolfo P and von Guggenberg E
Different attempts have been made in the past two decades to develop radiolabeled peptide conjugates with enhanced pharmacokinetic properties in order to improve the application for tumor imaging and peptide receptor radionuclide therapy (PRRT), which targets the cholecystokinin-2 receptor (CCK2R). In this paper, the influence of different side chain and peptide bond modifications has been explored for the minigastrin analog DOTA-DGlu-Ala-Tyr-Gly-Trp-(-Me)Nle-Asp-1Nal-NH (DOTA-MGS5). Based on this lead structure, five new derivatives were synthesized for radiolabeling with trivalent radiometals. Different chemical and biological properties of the new derivatives were analyzed. Receptor interaction of the peptide derivatives and cell internalization of the radiolabeled peptides were studied in A431-CCK2R cells. The stability of the radiolabeled peptides in vivo was investigated using BALB/c mice. Tumor targeting of all In-labeled peptide conjugates, and of a selected compound radiolabeled with gallium-68 and lutetium-177, was evaluated in BALB/c nude mice xenografted with A431-CCK2R and A431-mock cells. All In-labeled conjugates, except [In]In-DOTA-[Phe]MGS5, showed a high resistance against enzymatic degradation. A high receptor affinity with IC values in the low nanomolar range was confirmed for most of the peptide derivatives. The specific cell internalization over time was 35.3-47.3% for all radiopeptides 4 h after incubation. Only [In]In-DOTA-MGS5[NHCH] exhibited a lower cell internalization of 6.6 ± 2.8%. An overall improved resistance against enzymatic degradation was confirmed in vivo. Of the radiopeptides studied, [In]In-DOTA-[(-Me)1Nal]MGS5 showed the most promising targeting properties, with significantly increased accumulation of radioactivity in A431-CCK2R xenografts (48.1 ± 9.2% IA/g) and reduced accumulation of radioactivity in stomach (4.2 ± 0.5% IA/g). However, in comparison with DOTA-MGS5, a higher influence on the targeting properties was observed for the change of radiometal, resulting in a tumor uptake of 15.67 ± 2.21% IA/g for [Ga]Ga-DOTA-[(-Me)1Nal]MGS5 and 35.13 ± 6.32% IA/g for [Lu]Lu-DOTA-[(-Me)1Nal]MGS5.
Evaluation of the Efficacy of a Combined Treatment Using the mTOR-Inhibitor Everolimus and [177Lu]Lu-DOTA-TATE in Nude CD1 Mice with SSTR-Expressing Pancreatic AR42J Xenograft Tumors
Zellmer J, Yen HY, Kaiser L, Gildehaus FJ, Böning G, Steiger K, Hacker M, Bartenstein P, Todica A, Haug AR and Ilhan H
Evaluation of the Efficacy of a Combined Treatment Using the mTOR-Inhibitor Everolimus and [177Lu]Lu-DOTA-TATE in Nude CD1 Mice with SSTR-Expressing Pancreatic AR42J Xenograft Tumors
Zellmer J, Yen HY, Kaiser L, Gildehaus FJ, Böning G, Steiger K, Hacker M, Bartenstein P, Todica A, Haug AR and Ilhan H
Therapy options for advanced pancreatic neuroendocrine tumors (pNETs) include the mTOR inhibitor everolimus and peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE, however further optimization in the therapeutic landscape is required as response rates are still low. In this study, we investigated the synergistic and potentially enhanced efficacy of a combined treatment with everolimus and [177Lu]Lu-DOTA-TATE in a mouse model. Baseline [68Ga]Ga-DOTA-TATE PET scans were obtained five days after athymic CD1 mice were inoculated with AR42J tumor cells, before separating the animals into four groups. Group 1 received a placebo, group 2 everolimus, group 3 a placebo and PRRT, and group 4 everolimus and PRRT. The treatment response was monitored by manually measuring the tumor volumes (manual tumor volume, MTV) and conducting sequential [68Ga]Ga-DOTA-TATE PET scans at one, two, and four weeks after treatment induction. The biological tumor volume (BTV) was derived from PET scans using threshold-based volume of interest (VOI) measurements. Tracer uptake was measured semi-quantitatively as a tumor to background ratio (TBR). Mice were euthanized due to excessive tumor growth according to the ethics protocol; blood samples were drawn for the preparation of full blood counts and kidneys were obtained for histological analysis. For the histological assessment, a standardized score (renal damage score, RDS) was used. Full blood counts showed significantly increased numbers of neutrophils and lymphocytes in the groups receiving PRRT. All other parameters did not differ relevantly. In the histological analysis, groups receiving PRRT had a significantly higher RDS, whereas everolimus only tended to cause an increase in the RDS. Mice in groups 1 and 2 had to be euthanized due to excessive tumor growth two weeks after the start of the therapy, whereas follow-up in groups 3 and 4 comprised four weeks. PRRT significantly inhibited tumor growth; the administration of everolimus did not induce an additional effect. A good correlation existed between MTV and BTV. PRRT significantly reduced the TBR. [68Ga]Ga-DOTA-TATE PET is suitable for monitoring tumor growth in the applied model. The high efficacy of [177Lu]Lu-DOTA-TATE is not enhanced by the combination with everolimus.
Treatment patterns and oncological outcome of patients with advanced small intestinal neuroendocrine tumors: real-world data from the Medical University of Vienna
Melhorn P, Kretschmer-Chott E, Wolff L, Haug A, Mazal P, Raderer M and Kiesewetter B
Treatment patterns and oncological outcome of patients with advanced small intestinal neuroendocrine tumors: real-world data from the Medical University of Vienna
Melhorn P, Kretschmer-Chott E, Wolff L, Haug A, Mazal P, Raderer M and Kiesewetter B
Different oncological therapies have been approved for small intestinal neuroendocrine tumors (SI-NETs), but relatively little is known about efficacy and long-term outcome outside of phase III trials.
Theranostic in Nuclear Medicine - The paradigm of NET
Giammarile F
Theranostic in Nuclear Medicine - The paradigm of NET
Giammarile F
Theranostics is an emerging field in medicine that combines diagnostics and therapeutics into a single approach. Overall, theranostics represents a promising paradigm for personalized medicine, as it allows for targeted and precise treatment based on individual patient characteristics. In nuclear medicine, theranostics involves the use of radiopharmaceuticals that have both diagnostic and therapeutic properties. Moreover, theranostics in nuclear medicine offers several advantages over traditional cancer treatments. Unlike radiotherapy, in nuclear medicine the therapy is systemic that targets both primary tumors and metastatic lesions, offering a more comprehensive treatment approach. Additionally, nuclear medicine therapy has been shown to have fewer side effects compared to traditional chemotherapy, making it a more tolerable treatment option for patients. While theranostics in nuclear medicine is still a relatively new field, it has shown promising results in the treatment of neuroendocrine tumors (NETs). One example of a theranostic approach in nuclear medicine is the use of radiolabeled somatostatin analogs for the treatment of NETs. Somatostatin is a hormone that regulates the release of other hormones in the body. It also binds to somatostatin receptors, which are highly expressed in NETs. The first step in theranostics for NETs is the diagnosis and staging of the disease using a radiolabeled somatostatin analog and PET/CT imaging. This allows for the detection of the tumor and assessment of its size and location. Once the tumor has been identified, the same radiolabeled somatostatin analog can be used as a therapeutic agent. The radiopharmaceutical delivers radiation directly to the tumor cells, which destroys them while sparing surrounding healthy tissue. This is known as peptide receptor radionuclide therapy (PRRT). The use of theranostics in NETs also involves the identification of specific somatostatin receptor subtypes that are expressed in the tumor cells. This is important as different somatostatin analogs have varying affinities for different receptor subtypes. By selecting the appropriate radiolabeled somatostatin analog, clinicians can increase the specificity of the therapy, delivering radiation to the tumor cells while minimizing damage to healthy tissue. PRRT has been shown to be effective in treating NETs, particularly those that are resistant to other forms of treatment. It can also be used in combination with other therapies, such as chemotherapy and surgery, to improve outcomes. As research continues, it is likely that theranostics in nuclear medicine will become an increasingly important tool in the fight against cancer, particularly in the context of NETs, offering personalized, targeted treatment options that improve patient outcomes.