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
Feasibility and Optimal Time Point of [Ga]Gallium-labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography Imaging in Patients Undergoing Cytoreductive Surgery After Systemic Therapy for Primary Oligometastatic Prostate Cancer: Implications for Patient Selection and Extent of Surgery
Huebner N, Rasul S, Baltzer P, Clauser P, Hermann Grubmüller K, Mitterhauser M, Hacker M, Heidenreich A, Rajwa P, Fajkovic H, Shariat SF and Grubmüller B
Feasibility and Optimal Time Point of [Ga]Gallium-labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography Imaging in Patients Undergoing Cytoreductive Surgery After Systemic Therapy for Primary Oligometastatic Prostate Cancer: Implications for Patient Selection and Extent of Surgery
Huebner N, Rasul S, Baltzer P, Clauser P, Hermann Grubmüller K, Mitterhauser M, Hacker M, Heidenreich A, Rajwa P, Fajkovic H, Shariat SF and Grubmüller B
Prostate-specific membrane antigen (PSMA) targeted molecular imaging using positron emission tomography (PET) has significantly improved the diagnosis and treatment of prostate cancer (PCA).
Diagnostic Performance of Prostate-specific Membrane Antigen Positron Emission Tomography-targeted biopsy for Detection of Clinically Significant Prostate Cancer: A Systematic Review and Meta-analysis
Kawada T, Yanagisawa T, Rajwa P, Sari Motlagh R, Mostafaei H, Quhal F, Laukhtina E, Aydh A, König F, Pallauf M, Pradere B, Ceci F, Baltzer PAT, Hacker M, Rasul S, Karakiewicz PI, Araki M, Nasu Y and Shariat SF
Diagnostic Performance of Prostate-specific Membrane Antigen Positron Emission Tomography-targeted biopsy for Detection of Clinically Significant Prostate Cancer: A Systematic Review and Meta-analysis
Kawada T, Yanagisawa T, Rajwa P, Sari Motlagh R, Mostafaei H, Quhal F, Laukhtina E, Aydh A, König F, Pallauf M, Pradere B, Ceci F, Baltzer PAT, Hacker M, Rasul S, Karakiewicz PI, Araki M, Nasu Y and Shariat SF
Prostate-specific membrane antigen positron emission tomography (PSMA-PET) has gained acceptance as a staging tool for prostate cancer (PCa). Recent reports suggest an association between PSMA PET and detection of clinically significant PCa (csPCa) on prostate biopsy.
EANM-EAU consensus on PSMA PET/CT in respect to radioligand therapy ([Lu]Lu-PSMA)
Fanti S, Kunikowska J, Walz J, Witjes W and Bjartell A
EANM-EAU consensus on PSMA PET/CT in respect to radioligand therapy ([Lu]Lu-PSMA)
Fanti S, Kunikowska J, Walz J, Witjes W and Bjartell A
[F]FDG-PET/CT radiomics and artificial intelligence in lung cancer: Technical aspects and potential clinical applications
Manafi-Farid R, Askari E, Shiri I, Pirich C, Asadi M, Khateri M, Zaidi H and Beheshti M
[F]FDG-PET/CT radiomics and artificial intelligence in lung cancer: Technical aspects and potential clinical applications
Manafi-Farid R, Askari E, Shiri I, Pirich C, Asadi M, Khateri M, Zaidi H and Beheshti M
Lung cancer is the second most common cancer and the leading cause of cancer-related death worldwide. Molecular imaging using [F]fluorodeoxyglucose Positron Emission Tomography and/or Computed Tomography ([F]FDG-PET/CT) plays an essential role in the diagnosis, evaluation of response to treatment, and prediction of outcomes. The images are evaluated using qualitative and conventional quantitative indices. However, there is far more information embedded in the images, which can be extracted by sophisticated algorithms. Recently, the concept of uncovering and analyzing the invisible data extracted from medical images, called radiomics, is gaining more attention. Currently, [F]FDG-PET/CT radiomics is growingly evaluated in lung cancer to discover if it enhances the diagnostic performance or implication of [F]FDG-PET/CT in the management of lung cancer. In this review, we provide a short overview of the technical aspects, as they are discussed in different articles of this special issue. We mainly focus on the diagnostic performance of the [F]FDG-PET/CT-based radiomics and the role of artificial intelligence in non-small cell lung cancer, impacting the early detection, staging, prediction of tumor subtypes, biomarkers, and patient's outcomes.
Analysis of Cross-Combinations of Feature Selection and Machine-Learning Classification Methods Based on [F]F-FDG PET/CT Radiomic Features for Metabolic Response Prediction of Metastatic Breast Cancer Lesions
Gómez OV, Herraiz JL, Udías JM, Haug A, Papp L, Cioni D and Neri E
Analysis of Cross-Combinations of Feature Selection and Machine-Learning Classification Methods Based on [F]F-FDG PET/CT Radiomic Features for Metabolic Response Prediction of Metastatic Breast Cancer Lesions
Gómez OV, Herraiz JL, Udías JM, Haug A, Papp L, Cioni D and Neri E
This study aimed to identify optimal combinations between feature selection methods and machine-learning classifiers for predicting the metabolic response of individual metastatic breast cancer lesions, based on clinical variables and radiomic features extracted from pretreatment [F]F-FDG PET/CT images.
Use of PET Imaging to Assess the Efficacy of Thiethylperazine to Stimulate Cerebral MRP1 Transport Activity in Wild-Type and APP/PS1-21 Mice
Wölfl-Duchek M, Mairinger S, Hernández-Lozano I, Filip T, Zoufal V, Löbsch M, Stanek J, Kuntner C, Wanek T, Bauer M, Pahnke J and Langer O
Use of PET Imaging to Assess the Efficacy of Thiethylperazine to Stimulate Cerebral MRP1 Transport Activity in Wild-Type and APP/PS1-21 Mice
Wölfl-Duchek M, Mairinger S, Hernández-Lozano I, Filip T, Zoufal V, Löbsch M, Stanek J, Kuntner C, Wanek T, Bauer M, Pahnke J and Langer O
Multidrug resistance-associated protein 1 (MRP1, encoded by the gene) may contribute to the clearance of amyloid-beta (Aβ) peptides from the brain into the blood and stimulation of MRP1 transport activity may be a therapeutic approach to enhance brain Aβ clearance. In this study, we assessed the effect of thiethylperazine, an antiemetic drug which was shown to stimulate MRP1 activity in vitro and to decrease Aβ load in a rapid β-amyloidosis mouse model (APP/PS1-21), on MRP1 transport activity by means of positron emission tomography (PET) imaging with the MRP1 tracer 6-bromo-7-[C]methylpurine. Groups of wild-type, APP/PS1-21 and mice underwent PET scans before and after a 5-day oral treatment period with thiethylperazine (15 mg/kg, once daily). The elimination rate constant of radioactivity () was calculated from time-activity curves in the brain and the lungs as a measure of tissue MRP1 activity. Treatment with thiethylperazine had no significant effect on MRP1 activity in the brain and the lungs of wild-type and APP/PS1-21 mice. This may either be related to a lack of an MRP1-stimulating effect of thiethylperazine in vivo or to other factors, such as substrate-dependent MRP1 stimulation, insufficient target tissue exposure to thiethylperazine or limited sensitivity of the PET tracer to measure MRP1 stimulation.
Comparison of renal parenchymal trauma after standard, mini and ultra-mini percutaneous tract dilation in porcine models
Adamou C, Tsaturyan A, Kalogeropoulou C, Tzelepi V, Apostolopoulos D, Vretos T, Pagonis K, Peteinaris A, Liatsikos E and Kallidonis P
Comparison of renal parenchymal trauma after standard, mini and ultra-mini percutaneous tract dilation in porcine models
Adamou C, Tsaturyan A, Kalogeropoulou C, Tzelepi V, Apostolopoulos D, Vretos T, Pagonis K, Peteinaris A, Liatsikos E and Kallidonis P
To evaluate whether reducing tract dilation diameter in PCNL (percutaneous nephrolithotomy) procedures results in minimizing of renal trauma of the percutaneous tract.
Antitumour effects of apatinib in progressive, metastatic differentiated thyroid cancer (DTC)
Shi L, You Q, Wang J, Wang H, Li S, Tian R, Yao X, Wu W, Zhang L, Wang F, Lin Y and Li S
Antitumour effects of apatinib in progressive, metastatic differentiated thyroid cancer (DTC)
Shi L, You Q, Wang J, Wang H, Li S, Tian R, Yao X, Wu W, Zhang L, Wang F, Lin Y and Li S
Management of progressive, metastatic radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) has been a great challenge due to its poor prognosis and limited treatment options. Recently, apatinib, an orally anti-angiogenic tyrosine kinase inhibitor (TKI) is reported to be useful for treatment of progressive RAIR-DIC. The aim of this study was to evaluate the antitumour effect of apatinib and the combination therapy with radioactive iodine (RAI) in patients with progressive metastatic DTC.
Fast and memory-efficient reconstruction of sparse Poisson data in listmode with non-smooth priors with application to time-of-flight PET
Schramm G and Holler M
Fast and memory-efficient reconstruction of sparse Poisson data in listmode with non-smooth priors with application to time-of-flight PET
Schramm G and Holler M
Complete time of flight (TOF) sinograms of state-of-the-art TOF PET scanners have a large memory footprint. Currently, they contain ${\sim}4{\cdot}10^9$ data bins which amount to ${\sim}17$\,GB in 32\,bit floating point precision. Moreover, their size will continue to increase with advances in the achievable detector TOF resolution and increases in the axial field of view. Using iterative algorithms to reconstruct such enormous TOF sinograms becomes increasingly challenging due to the memory requirements and the computation time needed to evaluate the forward model for every data bin. This is especially true for more advanced optimization algorithms such as the stochastic primal-dual hybrid gradient (SPDHG) algorithm which allows for the use of non-smooth priors for regularization using subsets with guaranteed convergence. SPDHG requires the storage of additional sinograms in memory, which severely limits its application to data sets from state-of-the-art TOF PET systems using conventional computing hardware.
PET/MRI in the Presurgical Evaluation of Patients with Epilepsy: A Concordance Analysis
Borbély K, Emri M, Kenessey I, Tóth M, Singer J, Barsi P, Vajda Z, Pál E, Tóth Z, Beyer T, Dóczi T, Bajzik G, Fabó D, Janszky J, Jordán Z, Fajtai D, Kelemen A, Juhos V, Wintermark M, Nagy F, Moizs M, Nagy D, Lückl J and Repa I
PET/MRI in the Presurgical Evaluation of Patients with Epilepsy: A Concordance Analysis
Borbély K, Emri M, Kenessey I, Tóth M, Singer J, Barsi P, Vajda Z, Pál E, Tóth Z, Beyer T, Dóczi T, Bajzik G, Fabó D, Janszky J, Jordán Z, Fajtai D, Kelemen A, Juhos V, Wintermark M, Nagy F, Moizs M, Nagy D, Lückl J and Repa I
The aim of our prospective study was to evaluate the clinical impact of hybrid [F]-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging ([F]-FDG PET/MRI) on the decision workflow of epileptic patients with discordant electroclinical and MRI data. A novel mathematical model was introduced for a clinical concordance calculation supporting the classification of our patients by subgroups of clinical decisions. Fifty-nine epileptic patients with discordant clinical and diagnostic results or MRI negativity were included in this study. The diagnostic value of the PET/MRI was compared to other modalities of presurgical evaluation (e.g., electroclinical data, PET, and MRI). The results of the population-level statistical analysis of the introduced data fusion technique and concordance analysis demonstrated that this model could be the basis for the development of a more accurate clinical decision support parameter in the future. Therefore, making the establishment of "invasive" (operable and implantable) and "not eligible for any further invasive procedures" groups could be much more exact. Our results confirmed the relevance of PET/MRI with the diagnostic algorithm of presurgical evaluation. The introduction of a concordance analysis could be of high importance in clinical and surgical decision-making in the management of epileptic patients. Our study corroborated previous findings regarding the advantages of hybrid PET/MRI technology over MRI and electroclinical data.
Teilbereich PET
EANM-EAU consensus on PSMA PET/CT in respect to radioligand therapy ([Lu]Lu-PSMA)
Fanti S, Kunikowska J, Walz J, Witjes W and Bjartell A
EANM-EAU consensus on PSMA PET/CT in respect to radioligand therapy ([Lu]Lu-PSMA)
Fanti S, Kunikowska J, Walz J, Witjes W and Bjartell A
Feasibility and Optimal Time Point of [Ga]Gallium-labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography Imaging in Patients Undergoing Cytoreductive Surgery After Systemic Therapy for Primary Oligometastatic Prostate Cancer: Implications for Patient Selection and Extent of Surgery
Huebner N, Rasul S, Baltzer P, Clauser P, Hermann Grubmüller K, Mitterhauser M, Hacker M, Heidenreich A, Rajwa P, Fajkovic H, Shariat SF and Grubmüller B
Feasibility and Optimal Time Point of [Ga]Gallium-labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography Imaging in Patients Undergoing Cytoreductive Surgery After Systemic Therapy for Primary Oligometastatic Prostate Cancer: Implications for Patient Selection and Extent of Surgery
Huebner N, Rasul S, Baltzer P, Clauser P, Hermann Grubmüller K, Mitterhauser M, Hacker M, Heidenreich A, Rajwa P, Fajkovic H, Shariat SF and Grubmüller B
Prostate-specific membrane antigen (PSMA) targeted molecular imaging using positron emission tomography (PET) has significantly improved the diagnosis and treatment of prostate cancer (PCA).
Diagnostic Performance of Prostate-specific Membrane Antigen Positron Emission Tomography-targeted biopsy for Detection of Clinically Significant Prostate Cancer: A Systematic Review and Meta-analysis
Kawada T, Yanagisawa T, Rajwa P, Sari Motlagh R, Mostafaei H, Quhal F, Laukhtina E, Aydh A, König F, Pallauf M, Pradere B, Ceci F, Baltzer PAT, Hacker M, Rasul S, Karakiewicz PI, Araki M, Nasu Y and Shariat SF
Diagnostic Performance of Prostate-specific Membrane Antigen Positron Emission Tomography-targeted biopsy for Detection of Clinically Significant Prostate Cancer: A Systematic Review and Meta-analysis
Kawada T, Yanagisawa T, Rajwa P, Sari Motlagh R, Mostafaei H, Quhal F, Laukhtina E, Aydh A, König F, Pallauf M, Pradere B, Ceci F, Baltzer PAT, Hacker M, Rasul S, Karakiewicz PI, Araki M, Nasu Y and Shariat SF
Prostate-specific membrane antigen positron emission tomography (PSMA-PET) has gained acceptance as a staging tool for prostate cancer (PCa). Recent reports suggest an association between PSMA PET and detection of clinically significant PCa (csPCa) on prostate biopsy.
[F]FDG-PET/CT radiomics and artificial intelligence in lung cancer: Technical aspects and potential clinical applications
Manafi-Farid R, Askari E, Shiri I, Pirich C, Asadi M, Khateri M, Zaidi H and Beheshti M
[F]FDG-PET/CT radiomics and artificial intelligence in lung cancer: Technical aspects and potential clinical applications
Manafi-Farid R, Askari E, Shiri I, Pirich C, Asadi M, Khateri M, Zaidi H and Beheshti M
Lung cancer is the second most common cancer and the leading cause of cancer-related death worldwide. Molecular imaging using [F]fluorodeoxyglucose Positron Emission Tomography and/or Computed Tomography ([F]FDG-PET/CT) plays an essential role in the diagnosis, evaluation of response to treatment, and prediction of outcomes. The images are evaluated using qualitative and conventional quantitative indices. However, there is far more information embedded in the images, which can be extracted by sophisticated algorithms. Recently, the concept of uncovering and analyzing the invisible data extracted from medical images, called radiomics, is gaining more attention. Currently, [F]FDG-PET/CT radiomics is growingly evaluated in lung cancer to discover if it enhances the diagnostic performance or implication of [F]FDG-PET/CT in the management of lung cancer. In this review, we provide a short overview of the technical aspects, as they are discussed in different articles of this special issue. We mainly focus on the diagnostic performance of the [F]FDG-PET/CT-based radiomics and the role of artificial intelligence in non-small cell lung cancer, impacting the early detection, staging, prediction of tumor subtypes, biomarkers, and patient's outcomes.
Analysis of Cross-Combinations of Feature Selection and Machine-Learning Classification Methods Based on [F]F-FDG PET/CT Radiomic Features for Metabolic Response Prediction of Metastatic Breast Cancer Lesions
Gómez OV, Herraiz JL, Udías JM, Haug A, Papp L, Cioni D and Neri E
Analysis of Cross-Combinations of Feature Selection and Machine-Learning Classification Methods Based on [F]F-FDG PET/CT Radiomic Features for Metabolic Response Prediction of Metastatic Breast Cancer Lesions
Gómez OV, Herraiz JL, Udías JM, Haug A, Papp L, Cioni D and Neri E
This study aimed to identify optimal combinations between feature selection methods and machine-learning classifiers for predicting the metabolic response of individual metastatic breast cancer lesions, based on clinical variables and radiomic features extracted from pretreatment [F]F-FDG PET/CT images.
Use of PET Imaging to Assess the Efficacy of Thiethylperazine to Stimulate Cerebral MRP1 Transport Activity in Wild-Type and APP/PS1-21 Mice
Wölfl-Duchek M, Mairinger S, Hernández-Lozano I, Filip T, Zoufal V, Löbsch M, Stanek J, Kuntner C, Wanek T, Bauer M, Pahnke J and Langer O
Use of PET Imaging to Assess the Efficacy of Thiethylperazine to Stimulate Cerebral MRP1 Transport Activity in Wild-Type and APP/PS1-21 Mice
Wölfl-Duchek M, Mairinger S, Hernández-Lozano I, Filip T, Zoufal V, Löbsch M, Stanek J, Kuntner C, Wanek T, Bauer M, Pahnke J and Langer O
Multidrug resistance-associated protein 1 (MRP1, encoded by the gene) may contribute to the clearance of amyloid-beta (Aβ) peptides from the brain into the blood and stimulation of MRP1 transport activity may be a therapeutic approach to enhance brain Aβ clearance. In this study, we assessed the effect of thiethylperazine, an antiemetic drug which was shown to stimulate MRP1 activity in vitro and to decrease Aβ load in a rapid β-amyloidosis mouse model (APP/PS1-21), on MRP1 transport activity by means of positron emission tomography (PET) imaging with the MRP1 tracer 6-bromo-7-[C]methylpurine. Groups of wild-type, APP/PS1-21 and mice underwent PET scans before and after a 5-day oral treatment period with thiethylperazine (15 mg/kg, once daily). The elimination rate constant of radioactivity () was calculated from time-activity curves in the brain and the lungs as a measure of tissue MRP1 activity. Treatment with thiethylperazine had no significant effect on MRP1 activity in the brain and the lungs of wild-type and APP/PS1-21 mice. This may either be related to a lack of an MRP1-stimulating effect of thiethylperazine in vivo or to other factors, such as substrate-dependent MRP1 stimulation, insufficient target tissue exposure to thiethylperazine or limited sensitivity of the PET tracer to measure MRP1 stimulation.
Antitumour effects of apatinib in progressive, metastatic differentiated thyroid cancer (DTC)
Shi L, You Q, Wang J, Wang H, Li S, Tian R, Yao X, Wu W, Zhang L, Wang F, Lin Y and Li S
Antitumour effects of apatinib in progressive, metastatic differentiated thyroid cancer (DTC)
Shi L, You Q, Wang J, Wang H, Li S, Tian R, Yao X, Wu W, Zhang L, Wang F, Lin Y and Li S
Management of progressive, metastatic radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) has been a great challenge due to its poor prognosis and limited treatment options. Recently, apatinib, an orally anti-angiogenic tyrosine kinase inhibitor (TKI) is reported to be useful for treatment of progressive RAIR-DIC. The aim of this study was to evaluate the antitumour effect of apatinib and the combination therapy with radioactive iodine (RAI) in patients with progressive metastatic DTC.
Fast and memory-efficient reconstruction of sparse Poisson data in listmode with non-smooth priors with application to time-of-flight PET
Schramm G and Holler M
Fast and memory-efficient reconstruction of sparse Poisson data in listmode with non-smooth priors with application to time-of-flight PET
Schramm G and Holler M
Complete time of flight (TOF) sinograms of state-of-the-art TOF PET scanners have a large memory footprint. Currently, they contain ${\sim}4{\cdot}10^9$ data bins which amount to ${\sim}17$\,GB in 32\,bit floating point precision. Moreover, their size will continue to increase with advances in the achievable detector TOF resolution and increases in the axial field of view. Using iterative algorithms to reconstruct such enormous TOF sinograms becomes increasingly challenging due to the memory requirements and the computation time needed to evaluate the forward model for every data bin. This is especially true for more advanced optimization algorithms such as the stochastic primal-dual hybrid gradient (SPDHG) algorithm which allows for the use of non-smooth priors for regularization using subsets with guaranteed convergence. SPDHG requires the storage of additional sinograms in memory, which severely limits its application to data sets from state-of-the-art TOF PET systems using conventional computing hardware.
7T HR FID-MRSI Compared to Amino Acid PET: Glutamine and Glycine as Promising Biomarkers in Brain Tumors
Hangel G, Lazen P, Sharma S, Hristoska B, Cadrien C, Furtner J, Rausch I, Lipka A, Niess E, Hingerl L, Motyka S, Gruber S, Strasser B, Kiesel B, Preusser M, Roetzer-Pejrimovsky T, Wöhrer A, Bogner W, Widhalm G, Rössler K, Traub-Weidinger T and Trattnig S
7T HR FID-MRSI Compared to Amino Acid PET: Glutamine and Glycine as Promising Biomarkers in Brain Tumors
Hangel G, Lazen P, Sharma S, Hristoska B, Cadrien C, Furtner J, Rausch I, Lipka A, Niess E, Hingerl L, Motyka S, Gruber S, Strasser B, Kiesel B, Preusser M, Roetzer-Pejrimovsky T, Wöhrer A, Bogner W, Widhalm G, Rössler K, Traub-Weidinger T and Trattnig S
(1) Background: Recent developments in 7T magnetic resonance spectroscopic imaging (MRSI) made the acquisition of high-resolution metabolic images in clinically feasible measurement times possible. The amino acids glutamine (Gln) and glycine (Gly) were identified as potential neuro-oncological markers of importance. For the first time, we compared 7T MRSI to amino acid PET in a cohort of glioma patients. (2) Methods: In 24 patients, we co-registered 7T MRSI and routine PET and compared hotspot volumes of interest (VOI). We evaluated dice similarity coefficients (DSC), volume, center of intensity distance (CoI), median and threshold values for VOIs of PET and ratios of total choline (tCho), Gln, Gly, myo-inositol (Ins) to total N-acetylaspartate (tNAA) or total creatine (tCr). (3) Results: We found that Gln and Gly ratios generally resulted in a higher correspondence to PET than tCho. Using cutoffs of 1.6-times median values of a control region, DSCs to PET were 0.53 ± 0.36 for tCho/tNAA, 0.66 ± 0.40 for Gln/tNAA, 0.57 ± 0.36 for Gly/tNAA, and 0.38 ± 0.31 for Ins/tNAA. (4) Conclusions: Our 7T MRSI data corresponded better to PET than previous studies at lower fields. Our results for Gln and Gly highlight the importance of future research (e.g., using Gln PET tracers) into the role of both amino acids.
PET/MRI in the Presurgical Evaluation of Patients with Epilepsy: A Concordance Analysis
Borbély K, Emri M, Kenessey I, Tóth M, Singer J, Barsi P, Vajda Z, Pál E, Tóth Z, Beyer T, Dóczi T, Bajzik G, Fabó D, Janszky J, Jordán Z, Fajtai D, Kelemen A, Juhos V, Wintermark M, Nagy F, Moizs M, Nagy D, Lückl J and Repa I
PET/MRI in the Presurgical Evaluation of Patients with Epilepsy: A Concordance Analysis
Borbély K, Emri M, Kenessey I, Tóth M, Singer J, Barsi P, Vajda Z, Pál E, Tóth Z, Beyer T, Dóczi T, Bajzik G, Fabó D, Janszky J, Jordán Z, Fajtai D, Kelemen A, Juhos V, Wintermark M, Nagy F, Moizs M, Nagy D, Lückl J and Repa I
The aim of our prospective study was to evaluate the clinical impact of hybrid [F]-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging ([F]-FDG PET/MRI) on the decision workflow of epileptic patients with discordant electroclinical and MRI data. A novel mathematical model was introduced for a clinical concordance calculation supporting the classification of our patients by subgroups of clinical decisions. Fifty-nine epileptic patients with discordant clinical and diagnostic results or MRI negativity were included in this study. The diagnostic value of the PET/MRI was compared to other modalities of presurgical evaluation (e.g., electroclinical data, PET, and MRI). The results of the population-level statistical analysis of the introduced data fusion technique and concordance analysis demonstrated that this model could be the basis for the development of a more accurate clinical decision support parameter in the future. Therefore, making the establishment of "invasive" (operable and implantable) and "not eligible for any further invasive procedures" groups could be much more exact. Our results confirmed the relevance of PET/MRI with the diagnostic algorithm of presurgical evaluation. The introduction of a concordance analysis could be of high importance in clinical and surgical decision-making in the management of epileptic patients. Our study corroborated previous findings regarding the advantages of hybrid PET/MRI technology over MRI and electroclinical data.
Teilbereich SPECT
Comparison of renal parenchymal trauma after standard, mini and ultra-mini percutaneous tract dilation in porcine models
Adamou C, Tsaturyan A, Kalogeropoulou C, Tzelepi V, Apostolopoulos D, Vretos T, Pagonis K, Peteinaris A, Liatsikos E and Kallidonis P
Comparison of renal parenchymal trauma after standard, mini and ultra-mini percutaneous tract dilation in porcine models
Adamou C, Tsaturyan A, Kalogeropoulou C, Tzelepi V, Apostolopoulos D, Vretos T, Pagonis K, Peteinaris A, Liatsikos E and Kallidonis P
To evaluate whether reducing tract dilation diameter in PCNL (percutaneous nephrolithotomy) procedures results in minimizing of renal trauma of the percutaneous tract.
Transient cardioprotective effects of remote ischemic postconditioning on non-reperfused myocardial infarction: longitudinal evaluation study in pigs
Lu Y, Tian Y, Mou T, Zhou Y, Tian J, Yun M, Kiss A, Podesser BK, Hacker M, Zhang X and Li X
Transient cardioprotective effects of remote ischemic postconditioning on non-reperfused myocardial infarction: longitudinal evaluation study in pigs
Lu Y, Tian Y, Mou T, Zhou Y, Tian J, Yun M, Kiss A, Podesser BK, Hacker M, Zhang X and Li X
Remote ischemic postconditioning (RIPostC) has recently emerged as a potential novel therapeutic strategy to achieve protection against acute myocardial infarction (AMI) injury. We aimed to evaluate the longitudinal cardioprotective effects of RIPostC on AMI using Tc-MIBI SPECT myocardial perfusion imaging (MPI) and gated F-FDG PET (GPET) in pigs.
Cardiac sympathetic innervation in Parkinson's disease versus multiple system atrophy
Eckhardt C, Krismer F, Donnemiller E, Eschlböck S, Fanciulli A, Raccagni C, Bösch S, Mair K, Scherfler C, Djamshidian A, Uprimny C, Metzler B, Seppi K, Poewe W, Kiechl S, Virgolini I and Wenning GK
Cardiac sympathetic innervation in Parkinson's disease versus multiple system atrophy
Eckhardt C, Krismer F, Donnemiller E, Eschlböck S, Fanciulli A, Raccagni C, Bösch S, Mair K, Scherfler C, Djamshidian A, Uprimny C, Metzler B, Seppi K, Poewe W, Kiechl S, Virgolini I and Wenning GK
The aims of this study were to evaluate the diagnostic accuracy of the dual imaging method combining cardiac iodine--metaiodobenzylguanidine single-photon emission computed tomography combined with low-dose chest computed tomography compared to routine cardiac scintigraphy, and assess regional differences in tracer distribution and the relationships between imaging and autonomic function in Parkinson's disease and multiple system atrophy.
Diagnostic Value of Radiolabelled Somatostatin Analogues for Neuroendocrine Tumour Diagnosis: The Benefits and Drawbacks of [Cu]Cu-DOTA-TOC
Vahidfar N, Farzanehfar S, Abbasi M, Mirzaei S, Delpassand ES, Abbaspour F, Salehi Y, Biersack HJ and Ahmadzadehfar H
Diagnostic Value of Radiolabelled Somatostatin Analogues for Neuroendocrine Tumour Diagnosis: The Benefits and Drawbacks of [Cu]Cu-DOTA-TOC
Vahidfar N, Farzanehfar S, Abbasi M, Mirzaei S, Delpassand ES, Abbaspour F, Salehi Y, Biersack HJ and Ahmadzadehfar H
Neuroendocrine tumours (NETs) arise from secondary epithelial cell lines in the gastrointestinal or respiratory system organs. The rate of development of these tumours varies from an indolent to an aggressive course, typically being initially asymptomatic. The identification of these tumours is difficult, particularly because the primary tumour is often small and undetectable by conventional anatomical imaging. Consequently, diagnosis of NETs is complicated and has been a significant challenge until recently. In the last 30 years, the advent of novel nuclear medicine diagnostic procedures has led to a substantial increase in NET detection. Great varieties of exclusive single photon emission computed tomography (SPECT) and positron emission tomography (PET) radiopharmaceuticals for detecting NETs are being applied successfully in clinical settings, including [In]In-pentetreotide, [Tc]Tc-HYNIC-TOC/TATE, [Ga]Ga-DOTA-TATE, and [Cu]Cu-DOTA-TOC/TATE. Among these tracers for functional imaging, PET radiopharmaceuticals are clearly and substantially superior to planar or SPECT imaging radiopharmaceuticals. The main advantages include higher resolution, better sensitivity and increased lesion-to-background uptake. An advantage of diagnosis with a radiopharmaceutical is the capacity of theranostics to provide concomitant diagnosis and treatment with particulate radionuclides, such as beta and alpha emitters including Lutetium-177 (Lu) and Actinium-225 (Ac). Due to these unique challenges involved with diagnosing NETs, various PET tracers have been developed. This review compares the clinical characteristics of radiolabelled somatostatin analogues for NET diagnosis, focusing on the most recently FDA-approved [Cu]Cu-DOTA-TATE as a state-of-the art NET-PET/CT radiopharmaceutical.
Pragmatic Approach on Neuroimaging Techniques for the Differential Diagnosis of Parkinsonisms
Peralta C, Strafella AP, van Eimeren T, Ceravolo R, Seppi K, Kaasinen V, Arena JE, Lehericy S and
Pragmatic Approach on Neuroimaging Techniques for the Differential Diagnosis of Parkinsonisms
Peralta C, Strafella AP, van Eimeren T, Ceravolo R, Seppi K, Kaasinen V, Arena JE, Lehericy S and
Rapid advances in neuroimaging technologies in the exploration of the living human brain also apply to movement disorders. However, the accurate diagnosis of Parkinson's disease (PD) and atypical parkinsonian disorders (APDs) still remains a challenge in daily practice.
Radioiodination and Purification of [I]β-CIT and [I]FP-CIT with an Automated Radiosynthesizer
Plhak E, Gößnitzer E, Aigner RM and Kvaternik H
Radioiodination and Purification of [I]β-CIT and [I]FP-CIT with an Automated Radiosynthesizer
Plhak E, Gößnitzer E, Aigner RM and Kvaternik H
Dopaminergic transporter (DAT) imaging with single photon emission computed tomography (SPECT) is used to diagnose Parkinson's disease and to differentiate it from other neurodegenerative disorders without presynaptic dopaminergic dysfunction. The radioiodinated tropane alkaloids [I]FP-CIT and [I]β-CIT enable the evaluation of the integrity of DATs. Commonly, the labeling of these compounds is performed by electrophilic substitution of the alkylstannylated precursors with radioactive iodine and following purification by HPLC or solid phase extraction (SPE). This work presents the first radioiodination of β-CIT and FP-CIT with no carrier added [I]NaI on a Scintomics GRP synthesis module. Free iodine-131 and impurities were removed by SPE over a C-18 Sep-Pak cartridge. We achieved a radiochemical yield of >75% and a radiochemical purity of >98% with both compounds. Our development of an automated synthesis on a commercially available synthesizer ensures robust and efficient labeling of [I]FP-CIT and [I]β-CIT starting with low concentrated radioiodine.
Diagnostic Reference Levels for nuclear medicine imaging in Austria: A nationwide survey of used dose levels for adult patients
Wachabauer D, Beyer T, Ditto M, Gallowitsch HJ, Hinterreiter M, Ibi B, Malle P, Mirzaei S, Smetana F, Staudenherz A, Warwitz B, Zettinig G and Rausch I
Diagnostic Reference Levels for nuclear medicine imaging in Austria: A nationwide survey of used dose levels for adult patients
Wachabauer D, Beyer T, Ditto M, Gallowitsch HJ, Hinterreiter M, Ibi B, Malle P, Mirzaei S, Smetana F, Staudenherz A, Warwitz B, Zettinig G and Rausch I
To assess dose levels in routine nuclear medicine (NUC) procedures in Austria as a prior to a legislative update of the National Diagnostic Reference Levels (NDRL).
Prognostic value of divergent pattern detection by 99mTc-sestamibi gated SPECT in patients with anterior acute myocardial infarction
Calabretta R, Castello A, Giglioli C, Cecchi E, Cerisano G, Hacker M and Sciagrà R
Prognostic value of divergent pattern detection by 99mTc-sestamibi gated SPECT in patients with anterior acute myocardial infarction
Calabretta R, Castello A, Giglioli C, Cecchi E, Cerisano G, Hacker M and Sciagrà R
In gated myocardial perfusion SPECT, apical remodeling may be identified by the presence of a divergent pattern (DP) of the left ventricle (LV).
EANM recommendations based on systematic analysis of small animal radionuclide imaging in inflammatory musculoskeletal diseases
Aarntzen EHJG, Noriega-Álvarez E, Artiko V, Dias AH, Gheysens O, Glaudemans AWJM, Lauri C, Treglia G, van den Wyngaert T, van Leeuwen FWB and Terry SYA
EANM recommendations based on systematic analysis of small animal radionuclide imaging in inflammatory musculoskeletal diseases
Aarntzen EHJG, Noriega-Álvarez E, Artiko V, Dias AH, Gheysens O, Glaudemans AWJM, Lauri C, Treglia G, van den Wyngaert T, van Leeuwen FWB and Terry SYA
Inflammatory musculoskeletal diseases represent a group of chronic and disabling conditions that evolve from a complex interplay between genetic and environmental factors that cause perturbations in innate and adaptive immune responses. Understanding the pathogenesis of inflammatory musculoskeletal diseases is, to a large extent, derived from preclinical and basic research experiments. In vivo molecular imaging enables us to study molecular targets and to measure biochemical processes non-invasively and longitudinally, providing information on disease processes and potential therapeutic strategies, e.g. efficacy of novel therapeutic interventions, which is of complementary value next to ex vivo (post mortem) histopathological analysis and molecular assays. Remarkably, the large body of preclinical imaging studies in inflammatory musculoskeletal disease is in contrast with the limited reports on molecular imaging in clinical practice and clinical guidelines. Therefore, in this EANM-endorsed position paper, we performed a systematic review of the preclinical studies in inflammatory musculoskeletal diseases that involve radionuclide imaging, with a detailed description of the animal models used. From these reflections, we provide recommendations on what future studies in this field should encompass to facilitate a greater impact of radionuclide imaging techniques on the translation to clinical settings.
Improved Tumor-Targeting with Peptidomimetic Analogs of Minigastrin Lu-PP-F11N
Grob NM, Schibli R, Béhé M and Mindt TL
Improved Tumor-Targeting with Peptidomimetic Analogs of Minigastrin Lu-PP-F11N
Grob NM, Schibli R, Béhé M and Mindt TL
The cholecystokinin-2 receptor (CCK2R) is an attractive target in nuclear medicine due to its overexpression by different tumors. Several radiolabeled peptidic ligands targeting the CCK2R have been investigated in the past; however, their low stability against proteases can limit their uptake in tumors and metastases. Substitution of single or multiple amide bonds with metabolically stable 1,4-disubstituted 1,2,3-triazoles as amide bond bioisosteres proved a promising strategy for improving the tumor-targeting properties of a truncated analog of minigastrin. In this study, we applied the previously studied structural modifications to improve the pharmacokinetic and pharmacodynamic properties of PP-F11N, a minigastrin analog currently in clinical trials. Novel minigastrins (NMGs) as analogs of PP-F11N with one or two amide bonds substituted by 1,2,3-triazoles were synthesized, radiolabeled with Lu, and subjected to full evaluation in vitro (cell internalization, receptor affinity, stability in blood plasma) and in vivo (stability, biodistribution, SPECT/CT imaging). NMGs with triazoles inserted between the amino acids DGlu-Ala and/or Tyr-Gly showed a significantly increased cellular uptake and affinity toward the CCK2R in vitro. Resistance against the metabolic degradation of the NMGs was comparable to those of the clinical candidate PP-F11N. Imaging by SPECT/CT and biodistribution studies demonstrated a higher uptake in CCK2R-positive tumors but also in the CCK2R-positive stomach. The peptidomimetic compounds showed a slow tumor washout and high tumor-to-kidney ratios. The structural modifications led to the identification of analogs with promising properties for progression to clinical applications in the diagnosis and therapy of CCK2R-positive neoplasms.
Teilbereich Nuklearmedizinische Therapie
To give or not to give? A critical appraisal of a clinical trial on radioiodine treatment
Tuncel M, Vrachimis A, Campenni A, de Keizer B, Verburg FA, Kreissl MC, Ovcaricek PP, Geliashvili T and Giovanella L
To give or not to give? A critical appraisal of a clinical trial on radioiodine treatment
Tuncel M, Vrachimis A, Campenni A, de Keizer B, Verburg FA, Kreissl MC, Ovcaricek PP, Geliashvili T and Giovanella L
Clinical outcomes, Kadish-INSICA staging and therapeutic targeting of somatostatin receptor 2 in olfactory neuroblastoma
Lechner M, Takahashi Y, Turri-Zanoni M, Liu J, Counsell N, Hermsen M, Kaur RP, Zhao T, Ramanathan M, Schartinger VH, Emanuel O, Helman S, Varghese J, Dudas J, Riechelmann H, Sprung S, Haybaeck J, Howard D, Engel NW, Stewart S, Brooks L, Pickles JC, Jacques TS, Fenton TR, Williams L, Vaz FM, O'Flynn P, Stimpson P, Wang S, Hannan SA, Unadkat S, Hughes J, Dwivedi R, Forde CT, Randhawa P, Gane S, Joseph J, Andrews PJ, Royle G, Franchi A, Maragliano R, Battocchio S, Bewicke-Copley H, Pipinikas C, Webster A, Thirlwell C, Ho D, Teschendorff A, Zhu T, Steele CD, Pillay N, Vanhaesebroeck B, Mohyeldin A, Fernandez-Miranda J, Park KW, Le QT, West RB, Saade R, Manes RP, Omay SB, Vining EM, Judson BL, Yarbrough WG, Sansovini M, Silvia N, Grassi I, Bongiovanni A, Capper D, Schüller U, Thavaraj S, Sandison A, Surda P, Hopkins C, Ferrari M, Mattavelli D, Rampinelli V, Facchetti F, Nicolai P, Bossi P, Henriquez OA, Magliocca K, Solares CA, Wise SK, Llorente JL, Patel ZM, Nayak JV, Hwang PH, Lacy PD, Woods R, O'Neill JP, Jay A, Carnell D, Forster MD, Ishii M, London NR, Bell DM, Gallia GL, Castelnuovo P, Severi S, Lund VJ and Hanna EY
Clinical outcomes, Kadish-INSICA staging and therapeutic targeting of somatostatin receptor 2 in olfactory neuroblastoma
Lechner M, Takahashi Y, Turri-Zanoni M, Liu J, Counsell N, Hermsen M, Kaur RP, Zhao T, Ramanathan M, Schartinger VH, Emanuel O, Helman S, Varghese J, Dudas J, Riechelmann H, Sprung S, Haybaeck J, Howard D, Engel NW, Stewart S, Brooks L, Pickles JC, Jacques TS, Fenton TR, Williams L, Vaz FM, O'Flynn P, Stimpson P, Wang S, Hannan SA, Unadkat S, Hughes J, Dwivedi R, Forde CT, Randhawa P, Gane S, Joseph J, Andrews PJ, Royle G, Franchi A, Maragliano R, Battocchio S, Bewicke-Copley H, Pipinikas C, Webster A, Thirlwell C, Ho D, Teschendorff A, Zhu T, Steele CD, Pillay N, Vanhaesebroeck B, Mohyeldin A, Fernandez-Miranda J, Park KW, Le QT, West RB, Saade R, Manes RP, Omay SB, Vining EM, Judson BL, Yarbrough WG, Sansovini M, Silvia N, Grassi I, Bongiovanni A, Capper D, Schüller U, Thavaraj S, Sandison A, Surda P, Hopkins C, Ferrari M, Mattavelli D, Rampinelli V, Facchetti F, Nicolai P, Bossi P, Henriquez OA, Magliocca K, Solares CA, Wise SK, Llorente JL, Patel ZM, Nayak JV, Hwang PH, Lacy PD, Woods R, O'Neill JP, Jay A, Carnell D, Forster MD, Ishii M, London NR, Bell DM, Gallia GL, Castelnuovo P, Severi S, Lund VJ and Hanna EY
Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy.
Update on Preclinical Development and Clinical Translation of Cholecystokinin-2 Receptor Targeting Radiopharmaceuticals
von Guggenberg E, Kolenc P, Rottenburger C, Mikołajczak R and Hubalewska-Dydejczyk A
Update on Preclinical Development and Clinical Translation of Cholecystokinin-2 Receptor Targeting Radiopharmaceuticals
von Guggenberg E, Kolenc P, Rottenburger C, Mikołajczak R and Hubalewska-Dydejczyk A
The cholecystokinin-2 receptor (CCK2R) has been a target of interest for molecular imaging and targeted radionuclide therapy for two decades. However, so far CCK2R targeted imaging and therapy has not been introduced in clinical practice. Within this review the recent radiopharmaceutical development of CCK2R targeting compounds and the ongoing clinical trials are presented. Currently, new gastrin derivatives as well as nonpeptidic substances are being developed to improve the properties for clinical use. A team of specialists from the field of radiopharmacy and nuclear medicine reviewed the available literature and summarized their own experiences in the development and clinical testing of CCK2R targeting radiopharmaceuticals. The recent clinical trials with novel radiolabeled minigastrin analogs demonstrate the potential for both applications, imaging as well as targeted radiotherapy, and reinforce the clinical applicability within a theranostic concept. The intense efforts in optimizing CCK2R targeting radiopharmaceuticals has led to new substances for clinical use, as shown in first imaging studies in patients with advanced medullary thyroid cancer. The first clinical results suggest that the wider clinical implication of CCK2R-targeted radiopharmaceuticals is reasonable.
Nephrotoxicity and hematotoxicity one year after four cycles of peptide receptor radionuclide therapy (PRRT) and its impact on future treatment planning. A retrospective analysis
Nilica B, Svirydenka A, Fritz J, Bayerschmidt S, Kroiss AS, Gruber L and Virgolini IJ
Nephrotoxicity and hematotoxicity one year after four cycles of peptide receptor radionuclide therapy (PRRT) and its impact on future treatment planning. A retrospective analysis
Nilica B, Svirydenka A, Fritz J, Bayerschmidt S, Kroiss AS, Gruber L and Virgolini IJ
Nephro- and hematotoxicity after peptide receptor radionuclide therapy (PRRT) have been described in multiple studies with heterogeneous cumulative activities, number of cycles or radiolabelled peptides. Though highly differentiated metastasized neuroendocrine tumours (NET) have long progression free survival, they may progress. We analysed long-term side effects in a homogenous treatment schedule in PRRT-patients and their impact on future oncologic treatment in case of progression.
Theragnostics in Neuroendocrine Tumors
Rodrigues M, Svirydenka H and Virgolini I
Theragnostics in Neuroendocrine Tumors
Rodrigues M, Svirydenka H and Virgolini I
Several studies have demonstrated the effectiveness of somatostatin receptor (SSTR)-targeted imaging for diagnosis, staging, evaluating the possibility of treatment with cold somatostatin analogs, as well peptide receptor radionuclide therapy (PRRT), and evaluation of treatment response. PET with Ga-labeled somatostatin analogs provides excellent sensitivity and specificity for diagnosing and staging neuroendocrine tumors (NETs). Metabolic imaging with PET with fludeoxyglucose F/computed tomography (CT) complements the molecular imaging with Ga-SSTR PET/CT toward a personalized therapy in NET patients. The documented response rate of PRRT in NET summing up complete response, partial response, minor response, and stable disease is 70% to 80%.
High-Specific-Activity-I-MIBG versus Lu-DOTATATE Targeted Radionuclide Therapy for Metastatic Pheochromocytoma and Paraganglioma
Jha A, Taïeb D, Carrasquillo JA, Pryma DA, Patel M, Millo C, de Herder WW, Del Rivero J, Crona J, Shulkin BL, Virgolini I, Chen AP, Mittal BR, Basu S, Dillon JS, Hope TA, Mari Aparici C, Iagaru AH, Hicks RJ, Avram AM, Strosberg JR, Civelek AC, Lin FI, Pandit-Taskar N and Pacak K
High-Specific-Activity-I-MIBG versus Lu-DOTATATE Targeted Radionuclide Therapy for Metastatic Pheochromocytoma and Paraganglioma
Jha A, Taïeb D, Carrasquillo JA, Pryma DA, Patel M, Millo C, de Herder WW, Del Rivero J, Crona J, Shulkin BL, Virgolini I, Chen AP, Mittal BR, Basu S, Dillon JS, Hope TA, Mari Aparici C, Iagaru AH, Hicks RJ, Avram AM, Strosberg JR, Civelek AC, Lin FI, Pandit-Taskar N and Pacak K
Targeted radionuclide therapies (TRT) using I-metaiodobenzylguanidine (I-MIBG) and peptide receptor radionuclide therapy (Lu or Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocytoma/paraganglioma. Recently, high-specific-activity-I-MIBG therapy was approved by the FDA and both Lu-DOTATATE and I-MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochromocytoma/paraganglioma. However, a clinical dilemma often arises in the selection of TRT, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatin receptor imaging. To address this problem, we assembled a group of international experts, including oncologists, endocrinologists, and nuclear medicine physicians, with substantial experience in treating neuroendocrine tumors with TRTs to develop consensus and provide expert recommendations and perspectives on how to select between these two therapeutic options for metastatic/inoperable pheochromocytoma/paraganglioma. This article aims to summarize the survival outcomes of the available TRTs; discuss personalized treatment strategies based on functional imaging scans; address practical issues, including regulatory approvals; and compare toxicities and risk factors across treatments. Furthermore, it discusses the emerging TRTs.
Improved Tumor-Targeting with Peptidomimetic Analogs of Minigastrin Lu-PP-F11N
Grob NM, Schibli R, Béhé M and Mindt TL
Improved Tumor-Targeting with Peptidomimetic Analogs of Minigastrin Lu-PP-F11N
Grob NM, Schibli R, Béhé M and Mindt TL
The cholecystokinin-2 receptor (CCK2R) is an attractive target in nuclear medicine due to its overexpression by different tumors. Several radiolabeled peptidic ligands targeting the CCK2R have been investigated in the past; however, their low stability against proteases can limit their uptake in tumors and metastases. Substitution of single or multiple amide bonds with metabolically stable 1,4-disubstituted 1,2,3-triazoles as amide bond bioisosteres proved a promising strategy for improving the tumor-targeting properties of a truncated analog of minigastrin. In this study, we applied the previously studied structural modifications to improve the pharmacokinetic and pharmacodynamic properties of PP-F11N, a minigastrin analog currently in clinical trials. Novel minigastrins (NMGs) as analogs of PP-F11N with one or two amide bonds substituted by 1,2,3-triazoles were synthesized, radiolabeled with Lu, and subjected to full evaluation in vitro (cell internalization, receptor affinity, stability in blood plasma) and in vivo (stability, biodistribution, SPECT/CT imaging). NMGs with triazoles inserted between the amino acids DGlu-Ala and/or Tyr-Gly showed a significantly increased cellular uptake and affinity toward the CCK2R in vitro. Resistance against the metabolic degradation of the NMGs was comparable to those of the clinical candidate PP-F11N. Imaging by SPECT/CT and biodistribution studies demonstrated a higher uptake in CCK2R-positive tumors but also in the CCK2R-positive stomach. The peptidomimetic compounds showed a slow tumor washout and high tumor-to-kidney ratios. The structural modifications led to the identification of analogs with promising properties for progression to clinical applications in the diagnosis and therapy of CCK2R-positive neoplasms.
Consensus on molecular imaging and theranostics in neuroendocrine neoplasms
Ambrosini V, Kunikowska J, Baudin E, Bodei L, Bouvier C, Capdevila J, Cremonesi M, de Herder WW, Dromain C, Falconi M, Fani M, Fanti S, Hicks RJ, Kabasakal L, Kaltsas G, Lewington V, Minozzi S, Cinquini M, Öberg K, Oyen WJG, O'Toole D, Pavel M, Ruszniewski P, Scarpa A, Strosberg J, Sundin A, Taïeb D, Virgolini I, Wild D, Herrmann K and Yao J
Consensus on molecular imaging and theranostics in neuroendocrine neoplasms
Ambrosini V, Kunikowska J, Baudin E, Bodei L, Bouvier C, Capdevila J, Cremonesi M, de Herder WW, Dromain C, Falconi M, Fani M, Fanti S, Hicks RJ, Kabasakal L, Kaltsas G, Lewington V, Minozzi S, Cinquini M, Öberg K, Oyen WJG, O'Toole D, Pavel M, Ruszniewski P, Scarpa A, Strosberg J, Sundin A, Taïeb D, Virgolini I, Wild D, Herrmann K and Yao J
Nuclear medicine plays an increasingly important role in the management neuroendocrine neoplasms (NEN). Somatostatin analogue (SSA)-based positron emission tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy (PRRT) have been used in clinical trials and approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). European Association of Nuclear Medicine (EANM) Focus 3 performed a multidisciplinary Delphi process to deliver a balanced perspective on molecular imaging and radionuclide therapy in well-differentiated neuroendocrine tumours (NETs). NETs form in cells that interact with the nervous system or in glands that produce hormones. These cells, called neuroendocrine cells, can be found throughout the body, but NETs are most often found in the abdomen, especially in the gastrointestinal tract. These tumours may also be found in the lungs, pancreas and adrenal glands. In addition to being rare, NETs are also complex and may be difficult to diagnose. Most NETs are non-functioning; however, a minority present with symptoms related to hypersecretion of bioactive compounds. NETs often do not cause symptoms early in the disease process. When diagnosed, substantial number of patients are already found to have metastatic disease. Several societies' guidelines address Neuroendocrine neoplasms (NENs) management; however, many issues are still debated, due to both the difficulty in acquiring strong clinical evidence in a rare and heterogeneous disease and the different availability of diagnostic and therapeutic options across countries. EANM Focus 3 reached consensus on employing gallium-labelled somatostatin analogue ([Ga]Ga-DOTA-SSA)-based PET/CT with diagnostic CT or magnetic resonance imaging (MRI) for unknown primary NET detection, metastatic NET, NET staging/restaging, suspected extra-adrenal pheochromocytoma/paraganglioma and suspected paraganglioma. Consensus was reached on employing fluorine-fluoro-2-deoxyglucose ([F]FDG) PET/CT in neuroendocrine carcinoma, G3 NET and in G1-2 NET with mismatched lesions (CT-positive/[Ga]Ga-DOTA-SSA-negative). Peptide receptor radionuclide therapy (PRRT) was recommended for second line treatment for gastrointestinal NET with [Ga]Ga-DOTA-SSA uptake in all lesions, in G1/G2 NET at disease progression, and in a subset of G3 NET provided all lesions are positive at [F]FDG and [Ga]Ga-DOTA-SSA. PRRT rechallenge may be used for in patients with stable disease for at least 1 year after therapy completion. An international consensus is not only a prelude to a more standardised management across countries but also serves as a guide for the direction to follow when designing new research studies.
Long-Term Survival and Value of F-FDG PET/CT in Patients with Gastroenteropancreatic Neuroendocrine Tumors Treated with Second Peptide Receptor Radionuclide Therapy Course with Lu-DOTATATE
Rodrigues M, Winkler KK, Svirydenka H, Nilica B, Uprimny C and Virgolini I
Long-Term Survival and Value of F-FDG PET/CT in Patients with Gastroenteropancreatic Neuroendocrine Tumors Treated with Second Peptide Receptor Radionuclide Therapy Course with Lu-DOTATATE
Rodrigues M, Winkler KK, Svirydenka H, Nilica B, Uprimny C and Virgolini I
Peptide receptor radionuclide therapy (PRRT) has been recognized as a promising therapy against neuroendocrine tumors (NETs). The use of F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET) in NETs has been a matter of controversy. The purpose of this study was to evaluate the long-term survival and efficacy of a second PRRT course with Lu-DOTATE in patients with advanced gastroenteropancreatic (GEP) NETs. Furthermore, the value of F-FDG PET/CT in these patients was evaluated. 40 patients with GEP NETs who underwent two PRRT courses with Lu-DOTATATE and combined examinations with Ga-DOTA-TOC and F-FDG PET/CT were evaluated. After the second PRRT course, two patients (5.0%) were in partial remission, 21 patients (52.5%) in stable disease and 17 patients (42.5%) had progressive disease. The median overall survival was 122.10 months. After the second PRRT course, the median overall survival was significantly higher ( = 0.033) in the F-FDG-negative group compared to the F-FDG-positive group (145.50 versus 95.06 months, respectively). The median time to progression was 19.37 months. In conclusion, a second PRRT course with Lu-DOTATE is an effective treatment approach for GEP NET patients with disease progression. A change in F-FDG status after PRRT may predict the disease course and survival. Patients who are F-FDG-negative have a significantly longer overall survival than those who are F-FDG-positive.
Nephrotoxicity and hematotoxicity one year after four cycles of peptide receptor radionuclide therapy (PRRT) and its impact on future treatment planning - A retrospective analysis
Nilica B, Svirydenka A, Fritz J, Bayerschmidt S, Kroiss A, Gruber L and Virgolini IJ
Nephrotoxicity and hematotoxicity one year after four cycles of peptide receptor radionuclide therapy (PRRT) and its impact on future treatment planning - A retrospective analysis
Nilica B, Svirydenka A, Fritz J, Bayerschmidt S, Kroiss A, Gruber L and Virgolini IJ
Nephro- and hematotoxicity after peptide receptor radionuclide therapy (PRRT) have been described in multiple studies with heterogeneous cumulative activities, number of cycles or radiolabelled peptides. Though highly differentiated metastasized neuroendocrine tumours (NET) have long progression free survival, they may progress. We analysed long-term side effects in a homogenous treatment schedule in PRRT-patients and their impact on future oncologic treatment in case of progression.