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
18F-FDG and 68Ga-PSMA PET/CT in Paratesticular Mesothelioma
Kalantari F, Schweighofer-Zwink G, Rendl G, Pirich C and Beheshti M
18F-FDG and 68Ga-PSMA PET/CT in Paratesticular Mesothelioma
Kalantari F, Schweighofer-Zwink G, Rendl G, Pirich C and Beheshti M
A 66-year-old man with local prostate adenocarcinoma underwent radical prostatectomy (Gleason score 3 + 4 = 7, pT2c) in 2016. Four years later, he presented with a hydrocele and cystic atypical change in the left scrotum and soft tissue in the left groin. Final histopathology revealed spermatic cord mesothelioma and left hemangiosis carcinomatosa. A bone biopsy of the sacrum revealed infiltrates of a prostatic adenocarcinoma with small cell neuroendocrine differentiation. Dual-tracer PET/CT imaging using 18F-FDG and 68Ga-PSMA was able to identify local recurrence of scrotal mesothelioma and differentiate metastases of prostate cancer from malignant mesothelioma.
Nuclear imaging to visualize periodontal inflammation: Findings of a randomized controlled trial
Arefnia B, Horina A, Nazerani-Zemann T, Seinost G, Rieder M and Wimmer G
Nuclear imaging to visualize periodontal inflammation: Findings of a randomized controlled trial
Arefnia B, Horina A, Nazerani-Zemann T, Seinost G, Rieder M and Wimmer G
To investigate non-surgical periodontal therapy by 18F-fluorodeoxyglucose (2-[ F]FDG) uptake using positron emission tomography (PET) integrated with computed tomography (CT).
Subspace corrected relevance learning with application in neuroimaging
van Veen R, Tamboli NRB, Lövdal S, Meles SK, Renken RJ, de Vries GJ, Arnaldi D, Morbelli S, Clavero P, Obeso JA, Oroz MCR, Leenders KL, Villmann T and Biehl M
Subspace corrected relevance learning with application in neuroimaging
van Veen R, Tamboli NRB, Lövdal S, Meles SK, Renken RJ, de Vries GJ, Arnaldi D, Morbelli S, Clavero P, Obeso JA, Oroz MCR, Leenders KL, Villmann T and Biehl M
In machine learning, data often comes from different sources, but combining them can introduce extraneous variation that affects both generalization and interpretability. For example, we investigate the classification of neurodegenerative diseases using FDG-PET data collected from multiple neuroimaging centers. However, data collected at different centers introduces unwanted variation due to differences in scanners, scanning protocols, and processing methods. To address this issue, we propose a two-step approach to limit the influence of center-dependent variation on the classification of healthy controls and early vs. late-stage Parkinson's disease patients. First, we train a Generalized Matrix Learning Vector Quantization (GMLVQ) model on healthy control data to identify a "relevance space" that distinguishes between centers. Second, we use this space to construct a correction matrix that restricts a second GMLVQ system's training on the diagnostic problem. We evaluate the effectiveness of this approach on the real-world multi-center datasets and simulated artificial dataset. Our results demonstrate that the approach produces machine learning systems with reduced bias - being more specific due to eliminating information related to center differences during the training process - and more informative relevance profiles that can be interpreted by medical experts. This method can be adapted to similar problems outside the neuroimaging domain, as long as an appropriate "relevance space" can be identified to construct the correction matrix.
Development and Evaluation of Small-Molecule Ligands for Positron Emission Tomography of Immune Checkpoint Modulation Targeting Programmed Cell Death 1 Ligand 1
Bamminger K, Pichler V, Vraka C, Limberger T, Moneva B, Pallitsch K, Lieder B, Zacher AS, Ponti S, Benčurová K, Yang J, Högler S, Kodajova P, Kenner L, Hacker M and Wadsak W
Development and Evaluation of Small-Molecule Ligands for Positron Emission Tomography of Immune Checkpoint Modulation Targeting Programmed Cell Death 1 Ligand 1
Bamminger K, Pichler V, Vraka C, Limberger T, Moneva B, Pallitsch K, Lieder B, Zacher AS, Ponti S, Benčurová K, Yang J, Högler S, Kodajova P, Kenner L, Hacker M and Wadsak W
A substantial portion of patients do not benefit from programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) checkpoint inhibition therapies, necessitating a deeper understanding of predictive biomarkers. Immunohistochemistry (IHC) has played a pivotal role in assessing PD-L1 expression, but small-molecule positron emission tomography (PET) tracers could offer a promising avenue to address IHC-associated limitations, i.e., invasiveness and PD-L1 expression heterogeneity. PET tracers would allow for improved quantification of PD-L1 through noninvasive whole-body imaging, thereby enhancing patient stratification. Here, a large series of PD-L1 targeting small molecules were synthesized, leveraging advantageous substructures to achieve exceptionally low nanomolar affinities. Compound emerged as a promising candidate (IC = 10.2 nM) and underwent successful carbon-11 radiolabeling. However, a lack of tracer uptake in xenografts and notable accumulation in excretory organs was observed, underscoring the challenges encountered in small-molecule PD-L1 PET tracer development. The findings, including structure-activity relationships and biodistribution data, stand to illuminate the path forward for refining small-molecule PD-L1 PET tracers.
Challenges, Limitations and Pitfalls of PET and Advanced MRI in Patients with Brain Tumors - A Report of the PET/RANO Group
Galldiks N, Kaufmann TJ, Vollmuth P, Lohmann P, Smits M, Veronesi MC, Langen KJ, Rudá R, Albert NL, Hattingen E, Law I, Hutterer M, Soffietti R, Vogelbaum MA, Wen PY, Weller M and Tonn JC
Challenges, Limitations and Pitfalls of PET and Advanced MRI in Patients with Brain Tumors - A Report of the PET/RANO Group
Galldiks N, Kaufmann TJ, Vollmuth P, Lohmann P, Smits M, Veronesi MC, Langen KJ, Rudá R, Albert NL, Hattingen E, Law I, Hutterer M, Soffietti R, Vogelbaum MA, Wen PY, Weller M and Tonn JC
Brain tumor diagnostics have significantly evolved with the use of PET and advanced MRI techniques. In addition to anatomical MRI, these modalities may provide valuable information for several clinical applications such as differential diagnosis, delineation of tumor extent, prognostication, differentiation between tumor relapse and treatment-related changes, and the evaluation of response to anticancer therapy. In particular, joint recommendations of the RANO group, the EANO, and major European and American Nuclear Medicine societies highlighted that the additional clinical value of radiolabeled amino acids compared to anatomical MRI alone is outstanding and that its widespread clinical use should be supported. For advanced MRI and its steadily increasing use in clinical practice, the Standardization Subcommittee of the Jumpstarting Brain Tumor Drug Development Coalition provided more recently an updated acquisition protocol for the widely used dynamic susceptibility contrast perfusion MRI. Besides amino acid PET and perfusion MRI, other PET tracers and advanced MRI techniques (e.g., MR spectroscopy) are of considerable clinical interest and are increasingly integrated into everyday clinical practice. Nevertheless, these modalities have shortcomings which should be considered in clinical routine. This comprehensive review provides an overview of potential challenges, limitations and pitfalls associated with PET imaging and advanced MRI techniques in patients with gliomas or brain metastases. Despite these issues, PET imaging and advanced MRI techniques continue to play an indispensable role in brain tumor management. Acknowledging and mitigating these challenges through interdisciplinary collaboration, standardized protocols, and continuous innovation will further enhance the utility of these modalities in guiding optimal patient care.
Synthesis and preclinical evaluation of BOLD-100 radiolabeled with ruthenium-97 and ruthenium-103
Happl B, Balber T, Heffeter P, Denk C, Welch JM, Köster U, Alliot C, Bonraisin AC, Brandt M, Haddad F, Sterba JH, Kandioller W, Mitterhauser M, Hacker M, Keppler BK and Mindt TL
Synthesis and preclinical evaluation of BOLD-100 radiolabeled with ruthenium-97 and ruthenium-103
Happl B, Balber T, Heffeter P, Denk C, Welch JM, Köster U, Alliot C, Bonraisin AC, Brandt M, Haddad F, Sterba JH, Kandioller W, Mitterhauser M, Hacker M, Keppler BK and Mindt TL
BOLD-100 (formerly IT-139, KP1339), a well-established chemotherapeutic agent, is currently being investigated in clinical trials for the treatment of gastric, pancreatic, colorectal, and bile duct cancer. Despite numerous studies, the exact mode of action is still the subject of discussions. Radiolabeled BOLD-100 could be a powerful tool to clarify pharmacokinetic pathways of the compound and to predict therapy responses in patients using nuclear molecular imaging prior to the therapy. In this study, the radiosyntheses of carrier-added (c.a.) [Ru]BOLD-100 were performed with the two ruthenium isotopes ruthenium-103 (Ru; β, γ) and ruthenium-97 (Ru; EC, γ), of which in particular the latter isotope is suitable for imaging by single-photon emission computed tomography (SPECT). To identify the best tumor-to-background ratio for diagnostic imaging, biodistribution studies were performed with two different injected doses of c.a. [Ru]BOLD-100 (3 and 30 mg kg) in Balb/c mice bearing CT26 allografts over a time period of 72 h. Additionally, autoradiography of the tumors (24 h p.i.) was conducted. Our results indicate that the higher injected dose (30 mg kg) leads to more unspecific accumulation of the compound in non-targeted tissue, which is likely due to an overload of the albumin transport system. It was also shown that lower amounts of injected c.a. [Ru]BOLD-100 resulted in a relatively higher tumor uptake and, therefore, a better tumor-to-background ratio, which are encouraging results for future imaging studies using c.a. [Ru]BOLD-100.
[F]DPA-714-PET-MRI reveals pronounced innate immunity in human anti-LGI1 and anti-CASPR2 limbic encephalitis
Roll W, Bauer J, Dik A, Mueller C, Backhaus P, Räuber S, Zinnhardt B, Gallus M, Wimberley C, Körtvelyessy P, Schindler P, Stenzel W, Elger CE, Becker A, Lewerenz J, Wiendl H, Meuth SG, Schäfers M and Melzer N
[F]DPA-714-PET-MRI reveals pronounced innate immunity in human anti-LGI1 and anti-CASPR2 limbic encephalitis
Roll W, Bauer J, Dik A, Mueller C, Backhaus P, Räuber S, Zinnhardt B, Gallus M, Wimberley C, Körtvelyessy P, Schindler P, Stenzel W, Elger CE, Becker A, Lewerenz J, Wiendl H, Meuth SG, Schäfers M and Melzer N
Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: Agonist, Antagonist and Alternatives
Santo G, Di Santo G and Virgolini I
Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: Agonist, Antagonist and Alternatives
Santo G, Di Santo G and Virgolini I
Peptide receptor radionuclide therapy (PRRT) today is a well-established treatment strategy for patients with neuroendocrine tumors (NET). First performed already more than 30 years ago, PRRT was incorporated only in recent years into the major oncology guidelines, based on its proven efficacy and safety in clinical trials. Following the phase 3 NETTER-1 trial, which led to the final registration of the radiopharmaceutical Luthatera® for G1/G2 NET patients in 2017, the long-term results of the phase 3 NETTER-2 trial may pave the way for a new treatment option also for advanced G2/G3 patients as first-line therapy. The growing knowledge about the synergistic effect of combined therapies could also allow alternative (re)treatment options for NET patients, in order to create a tailored treatment strategy. The evolving thera(g)nostic concept could be applied for the identification of patients who might benefit from different image-guided treatment strategies. In this scenario, the use of dual tracer PET/CT in NET patients, using both [F]F-FDG/[Ga]Ga-DOTA-somatostatin analog (SSA) for diagnosis and follow-up, is under discussion and could also result in a powerful prognostic tool. In addition, alternative strategies based on different metabolic pathways, radioisotopes, or combinations of different medical approaches could be applied. A number of different promising "doors" could thus open in the near future for the treatment of NET patients - and the "key" will be thera(g)nostic!
Non-invasive assessment of stimulation-specific changes in cerebral glucose metabolism with functional PET
Godbersen GM, Falb P, Klug S, Silberbauer LR, Reed MB, Nics L, Hacker M, Lanzenberger R and Hahn A
Non-invasive assessment of stimulation-specific changes in cerebral glucose metabolism with functional PET
Godbersen GM, Falb P, Klug S, Silberbauer LR, Reed MB, Nics L, Hacker M, Lanzenberger R and Hahn A
Functional positron emission tomography (fPET) with [F]FDG allows quantification of stimulation-induced changes in glucose metabolism independent of neurovascular coupling. However, the gold standard for quantification requires invasive arterial blood sampling, limiting its widespread use. Here, we introduce a novel fPET method without the need for an input function.
EANM practice guidelines for an appropriate use of PET and SPECT for patients with epilepsy
Traub-Weidinger T, Arbizu J, Barthel H, Boellaard R, Borgwardt L, Brendel M, Cecchin D, Chassoux F, Fraioli F, Garibotto V, Guedj E, Hammers A, Law I, Morbelli S, Tolboom N, Van Weehaeghe D, Verger A, Van Paesschen W, von Oertzen TJ, Zucchetta P and Semah F
EANM practice guidelines for an appropriate use of PET and SPECT for patients with epilepsy
Traub-Weidinger T, Arbizu J, Barthel H, Boellaard R, Borgwardt L, Brendel M, Cecchin D, Chassoux F, Fraioli F, Garibotto V, Guedj E, Hammers A, Law I, Morbelli S, Tolboom N, Van Weehaeghe D, Verger A, Van Paesschen W, von Oertzen TJ, Zucchetta P and Semah F
Epilepsy is one of the most frequent neurological conditions with an estimated prevalence of more than 50 million people worldwide and an annual incidence of two million. Although pharmacotherapy with anti-seizure medication (ASM) is the treatment of choice, ~30% of patients with epilepsy do not respond to ASM and become drug resistant. Focal epilepsy is the most frequent form of epilepsy. In patients with drug-resistant focal epilepsy, epilepsy surgery is a treatment option depending on the localisation of the seizure focus for seizure relief or seizure freedom with consecutive improvement in quality of life. Beside examinations such as scalp video/electroencephalography (EEG) telemetry, structural, and functional magnetic resonance imaging (MRI), which are primary standard tools for the diagnostic work-up and therapy management of epilepsy patients, molecular neuroimaging using different radiopharmaceuticals with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) influences and impacts on therapy decisions. To date, there are no literature-based praxis recommendations for the use of Nuclear Medicine (NM) imaging procedures in epilepsy. The aims of these guidelines are to assist in understanding the role and challenges of radiotracer imaging for epilepsy; to provide practical information for performing different molecular imaging procedures for epilepsy; and to provide an algorithm for selecting the most appropriate imaging procedures in specific clinical situations based on current literature. These guidelines are written and authorized by the European Association of Nuclear Medicine (EANM) to promote optimal epilepsy imaging, especially in the presurgical setting in children, adolescents, and adults with focal epilepsy. They will assist NM healthcare professionals and also specialists such as Neurologists, Neurophysiologists, Neurosurgeons, Psychiatrists, Psychologists, and others involved in epilepsy management in the detection and interpretation of epileptic seizure onset zone (SOZ) for further treatment decision. The information provided should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals and imaging modalities.
Teilbereich SPECT
Disparities in Noninvasive Traditional and Advanced Testing for Coronary Artery Disease: Findings from the INCAPS-COVID 2 Study
Villines TC, Rodriguez-Lozano P, Mallawaarachchi I, Williams MC, Hirschfeld C, Better N, Shaw LJ, Vitola JV, Cerci RJ, Dorbala S, Bucciarelli-Ducci C, Karthikeyan G, Cohen YA, Malkovskiy E, Randazzo MJ, Choi AD, Pascual TNB, Pynda Y, Dondi M, Paez D, Einstein AJ and
Disparities in Noninvasive Traditional and Advanced Testing for Coronary Artery Disease: Findings from the INCAPS-COVID 2 Study
Villines TC, Rodriguez-Lozano P, Mallawaarachchi I, Williams MC, Hirschfeld C, Better N, Shaw LJ, Vitola JV, Cerci RJ, Dorbala S, Bucciarelli-Ducci C, Karthikeyan G, Cohen YA, Malkovskiy E, Randazzo MJ, Choi AD, Pascual TNB, Pynda Y, Dondi M, Paez D, Einstein AJ and
The COVID-19 pandemic disrupted the delivery of cardiovascular care, including noninvasive testing protocols and test selection for the evaluation of coronary artery disease (CAD). Trends in test selection in traditional versus advanced noninvasive tests for CAD during the pandemic and in countries of varying income status have not been well studied. The International Atomic Energy Agency conducted a global survey to assess the pandemic-related changes in the practice of cardiovascular diagnostic testing. Site procedural volumes for noninvasive tests to evaluate CAD from March 2019 (prepandemic), April 2020 (onset), and April 2021 (initial recovery) were collected. We considered traditional testing modalities, such as exercise electrocardiography, stress echocardiography, and stress single-photon emission computed tomography, and advanced testing modalities, such as stress cardiac magnetic resonance, coronary computed tomography angiography, and stress positron emission tomography. Survey data were obtained from 669 centers in 107 countries, reporting the performance of 367,933 studies for CAD during the study period. Compared with 2019, traditional tests were performed 14% less frequently (recovery rate 82%) in 2021 versus advanced tests, which were performed 15% more frequently (128% recovery rate). Coronary computed tomography angiography, stress cardiac magnetic resonance, and stress positron emission tomography showed 14%, 25%, and 25% increases in volumes from 2019 to 2021, respectively. The increase in advanced testing was isolated to high- and upper middle-income countries, with 132% recovery in advanced tests by 2021 compared with 55% in lower income nations. The COVID-19 pandemic exacerbated economic disparities in CAD testing practice between wealthy and poorer countries. Greater recovery rates and even new growth were observed for advanced imaging modalities; however, this growth was restricted to wealthy countries. Efforts to reduce practice variations in CAD testing because of economic status are warranted.
Neurological Disorders and Women's Health: Contribution of Molecular Neuroimaging Techniques
Ekmekcioglu O, Albert NL, Heinrich K, Tolboom N, Van Weehaeghe D, Traub-Weidinger T, Atay LO, Garibotto V and Morbelli S
Neurological Disorders and Women's Health: Contribution of Molecular Neuroimaging Techniques
Ekmekcioglu O, Albert NL, Heinrich K, Tolboom N, Van Weehaeghe D, Traub-Weidinger T, Atay LO, Garibotto V and Morbelli S
Sex differences in brain physiology and the mechanisms of drug action have been extensively reported. These biological variances, from structure to hormonal and genetic aspects, can profoundly influence healthy functioning and disease mechanisms and might have implications for treatment and drug development. Molecular neuroimaging techniques may help to disclose sex's impact on brain functioning, as well as the neuropathological changes underpinning several diseases. This narrative review summarizes recent lines of evidence based on PET and SPECT imaging, highlighting sex differences in normal conditions and various neurological disorders.
Synthesis and preclinical evaluation of BOLD-100 radiolabeled with ruthenium-97 and ruthenium-103
Happl B, Balber T, Heffeter P, Denk C, Welch JM, Köster U, Alliot C, Bonraisin AC, Brandt M, Haddad F, Sterba JH, Kandioller W, Mitterhauser M, Hacker M, Keppler BK and Mindt TL
Synthesis and preclinical evaluation of BOLD-100 radiolabeled with ruthenium-97 and ruthenium-103
Happl B, Balber T, Heffeter P, Denk C, Welch JM, Köster U, Alliot C, Bonraisin AC, Brandt M, Haddad F, Sterba JH, Kandioller W, Mitterhauser M, Hacker M, Keppler BK and Mindt TL
BOLD-100 (formerly IT-139, KP1339), a well-established chemotherapeutic agent, is currently being investigated in clinical trials for the treatment of gastric, pancreatic, colorectal, and bile duct cancer. Despite numerous studies, the exact mode of action is still the subject of discussions. Radiolabeled BOLD-100 could be a powerful tool to clarify pharmacokinetic pathways of the compound and to predict therapy responses in patients using nuclear molecular imaging prior to the therapy. In this study, the radiosyntheses of carrier-added (c.a.) [Ru]BOLD-100 were performed with the two ruthenium isotopes ruthenium-103 (Ru; β, γ) and ruthenium-97 (Ru; EC, γ), of which in particular the latter isotope is suitable for imaging by single-photon emission computed tomography (SPECT). To identify the best tumor-to-background ratio for diagnostic imaging, biodistribution studies were performed with two different injected doses of c.a. [Ru]BOLD-100 (3 and 30 mg kg) in Balb/c mice bearing CT26 allografts over a time period of 72 h. Additionally, autoradiography of the tumors (24 h p.i.) was conducted. Our results indicate that the higher injected dose (30 mg kg) leads to more unspecific accumulation of the compound in non-targeted tissue, which is likely due to an overload of the albumin transport system. It was also shown that lower amounts of injected c.a. [Ru]BOLD-100 resulted in a relatively higher tumor uptake and, therefore, a better tumor-to-background ratio, which are encouraging results for future imaging studies using c.a. [Ru]BOLD-100.
EANM practice guidelines for an appropriate use of PET and SPECT for patients with epilepsy
Traub-Weidinger T, Arbizu J, Barthel H, Boellaard R, Borgwardt L, Brendel M, Cecchin D, Chassoux F, Fraioli F, Garibotto V, Guedj E, Hammers A, Law I, Morbelli S, Tolboom N, Van Weehaeghe D, Verger A, Van Paesschen W, von Oertzen TJ, Zucchetta P and Semah F
EANM practice guidelines for an appropriate use of PET and SPECT for patients with epilepsy
Traub-Weidinger T, Arbizu J, Barthel H, Boellaard R, Borgwardt L, Brendel M, Cecchin D, Chassoux F, Fraioli F, Garibotto V, Guedj E, Hammers A, Law I, Morbelli S, Tolboom N, Van Weehaeghe D, Verger A, Van Paesschen W, von Oertzen TJ, Zucchetta P and Semah F
Epilepsy is one of the most frequent neurological conditions with an estimated prevalence of more than 50 million people worldwide and an annual incidence of two million. Although pharmacotherapy with anti-seizure medication (ASM) is the treatment of choice, ~30% of patients with epilepsy do not respond to ASM and become drug resistant. Focal epilepsy is the most frequent form of epilepsy. In patients with drug-resistant focal epilepsy, epilepsy surgery is a treatment option depending on the localisation of the seizure focus for seizure relief or seizure freedom with consecutive improvement in quality of life. Beside examinations such as scalp video/electroencephalography (EEG) telemetry, structural, and functional magnetic resonance imaging (MRI), which are primary standard tools for the diagnostic work-up and therapy management of epilepsy patients, molecular neuroimaging using different radiopharmaceuticals with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) influences and impacts on therapy decisions. To date, there are no literature-based praxis recommendations for the use of Nuclear Medicine (NM) imaging procedures in epilepsy. The aims of these guidelines are to assist in understanding the role and challenges of radiotracer imaging for epilepsy; to provide practical information for performing different molecular imaging procedures for epilepsy; and to provide an algorithm for selecting the most appropriate imaging procedures in specific clinical situations based on current literature. These guidelines are written and authorized by the European Association of Nuclear Medicine (EANM) to promote optimal epilepsy imaging, especially in the presurgical setting in children, adolescents, and adults with focal epilepsy. They will assist NM healthcare professionals and also specialists such as Neurologists, Neurophysiologists, Neurosurgeons, Psychiatrists, Psychologists, and others involved in epilepsy management in the detection and interpretation of epileptic seizure onset zone (SOZ) for further treatment decision. The information provided should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals and imaging modalities.
Quality Assurance Considerations in Radiopharmaceutical Therapy Dosimetry Using PLANETDose: An International Atomic Energy Agency Study
Kayal G, Barbosa N, Marín CC, Ferrer L, Fragoso-Negrín JA, Grosev D, Gupta SK, Hidayati NR, Moalosi TCG, Poli GL, Thakral P, Tsapaki V, Vauclin S, Vergara-Gil A, Knoll P, Hobbs RF and Bardiès M
Quality Assurance Considerations in Radiopharmaceutical Therapy Dosimetry Using PLANETDose: An International Atomic Energy Agency Study
Kayal G, Barbosa N, Marín CC, Ferrer L, Fragoso-Negrín JA, Grosev D, Gupta SK, Hidayati NR, Moalosi TCG, Poli GL, Thakral P, Tsapaki V, Vauclin S, Vergara-Gil A, Knoll P, Hobbs RF and Bardiès M
Implementation of radiopharmaceutical therapy dosimetry varies depending on the clinical application, dosimetry protocol, software, and ultimately the operator. Assessing clinical dosimetry accuracy and precision is therefore a challenging task. This work emphasizes some pitfalls encountered during a structured analysis, performed on a single-patient dataset consisting of SPECT/CT images by various participants using a standard protocol and clinically approved commercial software. The clinical dataset consisted of the dosimetric study of a patient administered with [Lu]Lu-DOTATATE at Tygerberg Hospital, South Africa, as a part of International Atomic Energy Agency-coordinated research project E23005. SPECT/CT images were acquired at 5 time points postinjection. Patient and calibration images were reconstructed on a workstation, and a calibration factor of 122.6 Bq/count was derived independently and provided to the participants. A standard dosimetric protocol was defined, and PLANETDose (version 3.1.1) software was installed at 9 centers to perform the dosimetry of 3 treatment cycles. The protocol included rigid image registration, segmentation (semimanual for organs, activity threshold for tumors), and dose voxel kernel convolution of activity followed by absorbed dose (AD) rate integration to obtain the ADs. Iterations of the protocol were performed by participants individually and within collective training, the results of which were analyzed for dosimetric variability, as well as for quality assurance and error analysis. Intermediary checkpoints were developed to understand possible sources of variation and to differentiate user error from legitimate user variability. Initial dosimetric results for organs (liver and kidneys) and lesions showed considerable interoperator variability. Not only was the generation of intermediate checkpoints such as total counts, volumes, and activity required, but also activity-to-count ratio, activity concentration, and AD rate-to-activity concentration ratio to determine the source of variability. When the same patient dataset was analyzed using the same dosimetry procedure and software, significant disparities were observed in the results despite multiple sessions of training and feedback. Variations due to human error could be minimized or avoided by performing intensive training sessions, establishing intermediate checkpoints, conducting sanity checks, and cross-validating results across physicists or with standardized datasets. This finding promotes the development of quality assurance in clinical dosimetry.
SPECT/CT, PET/CT, and PET/MRI for Response Assessment of Bone Metastases
Zamani-Siahkali N, Mirshahvalad SA, Farbod A, Divband G, Pirich C, Veit-Haibach P, Cook G and Beheshti M
SPECT/CT, PET/CT, and PET/MRI for Response Assessment of Bone Metastases
Zamani-Siahkali N, Mirshahvalad SA, Farbod A, Divband G, Pirich C, Veit-Haibach P, Cook G and Beheshti M
Recent developments in hybrid SPECT/CT systems and the use of cadmium-zinc-telluride (CZT) detectors have improved the diagnostic accuracy of bone scintigraphy. These advancements have paved the way for novel quantitative approaches to accurate and reproducible treatment monitoring of bone metastases. PET/CT imaging using [F]F-FDG and [F]F-NaF have shown promising clinical utility in bone metastases assessment and monitoring response to therapy and prediction of treatment response in a broad range of malignancies. Additionally, specific tumor-targeting tracers like [Tc]Tc-PSMA, [Ga]Ga-PSMA, or [C]C- or [F]F-Choline revealed high diagnostic performance for early assessment and prognostication of bone metastases, particularly in prostate cancer. PET/MRI appears highly accurate imaging modality, but has associated limitations notably, limited availability, more complex logistics and high installation costs. Advances in artificial intelligence (Al) seem to improve the accuracy of imaging modalities and provide an assistant role in the evaluation of treatment response of bone metastases.
Molecular image-guided surgery in gynaecological cancer: where do we stand?
Pisano G, Wendler T, Valdés Olmos RA, Garganese G, Rietbergen DDD, Giammarile F, Vidal-Sicart S, Oonk MHM, Frumovitz M, Abu-Rustum NR, Scambia G, Rufini V and Collarino A
Molecular image-guided surgery in gynaecological cancer: where do we stand?
Pisano G, Wendler T, Valdés Olmos RA, Garganese G, Rietbergen DDD, Giammarile F, Vidal-Sicart S, Oonk MHM, Frumovitz M, Abu-Rustum NR, Scambia G, Rufini V and Collarino A
The aim of this review is to give an overview of the current status of molecular image-guided surgery in gynaecological malignancies, from both clinical and technological points of view.
Enhancing Interoperability and Harmonisation of Nuclear Medicine Image Data and Associated Clinical Data
Fuchs T, Kaiser L, Müller D, Papp L, Fischer R and Tran-Gia J
Enhancing Interoperability and Harmonisation of Nuclear Medicine Image Data and Associated Clinical Data
Fuchs T, Kaiser L, Müller D, Papp L, Fischer R and Tran-Gia J
Nuclear imaging techniques such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) in combination with computed tomography (CT) are established imaging modalities in clinical practice, particularly for oncological problems. Due to a multitude of manufacturers, different measurement protocols, local demographic or clinical workflow variations as well as various available reconstruction and analysis software, very heterogeneous datasets are generated. This review article examines the current state of interoperability and harmonisation of image data and related clinical data in the field of nuclear medicine. Various approaches and standards to improve data compatibility and integration are discussed. These include, for example, structured clinical history, standardisation of image acquisition and reconstruction as well as standardised preparation of image data for evaluation. Approaches to improve data acquisition, storage and analysis will be presented. Furthermore, approaches are presented to prepare the datasets in such a way that they become usable for projects applying artificial intelligence (AI) (machine learning, deep learning, etc.). This review article concludes with an outlook on future developments and trends related to AI in nuclear medicine, including a brief research of commercial solutions.
Head-to-Head Comparison of CZT-SPECT and SPECT/CT Myocardial Perfusion Imaging: Interobserver and Intraobserver Agreement and Diagnostic Performance
Kalantari F, Mohseninia N, Wetsch A, Harsini S, Hehenwarter L, Schweighofer-Zwink G, Zamani-Siahkali N, Rendl G, Beheshti M and Pirich C
Head-to-Head Comparison of CZT-SPECT and SPECT/CT Myocardial Perfusion Imaging: Interobserver and Intraobserver Agreement and Diagnostic Performance
Kalantari F, Mohseninia N, Wetsch A, Harsini S, Hehenwarter L, Schweighofer-Zwink G, Zamani-Siahkali N, Rendl G, Beheshti M and Pirich C
Myocardial perfusion imaging (MPI) plays a crucial role in diagnosing coronary artery disease (CAD), with single-photon emission computed tomography (SPECT) being a widely accepted method. The accuracy of MPI relies on image quality and the expertise of physicians. While CZT-SPECT cameras offer advantages, they can be susceptible to attenuation artifacts. Therefore, our objective was to evaluate the diagnostic accuracy of CZT-SPECT and SPECT/CT in a clinical setting.
Theranostics with photodynamic therapy for personalized medicine: to see and to treat
Wang Y, Staudinger JN, Mindt TL and Gasser G
Theranostics with photodynamic therapy for personalized medicine: to see and to treat
Wang Y, Staudinger JN, Mindt TL and Gasser G
Photodynamic Therapy (PDT) is an approved treatment modality, which is presently receiving great attention due to its limited invasiveness, high selectivity and limited susceptibility to drug resistance. Another related research area currently expanding rapidly is the development of novel theranostic agents based on the combination of PDT with different imaging technologies, which allows for both therapy and diagnosis. This combination can help to address issues of suboptimal biodistribution and selectivity through regional imaging, while therapeutic agents enable an effective and personalized therapy. In this review, we describe compounds, whose structures combine PDT photosensitizers with different imaging probes - including examples for near-infrared optical imaging, magnetic resonance imaging (MRI) and nuclear imaging (PET or SPECT), generating novel theranostic drug candidates. We have intentionally focused our attention on novel compounds, which have already been investigated preclinically in order to demonstrate the potential of such theranostic agents for clinical applications.
Teilbereich Nuklearmedizinische Therapie
Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: Agonist, Antagonist and Alternatives
Santo G, Di Santo G and Virgolini I
Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: Agonist, Antagonist and Alternatives
Santo G, Di Santo G and Virgolini I
Peptide receptor radionuclide therapy (PRRT) today is a well-established treatment strategy for patients with neuroendocrine tumors (NET). First performed already more than 30 years ago, PRRT was incorporated only in recent years into the major oncology guidelines, based on its proven efficacy and safety in clinical trials. Following the phase 3 NETTER-1 trial, which led to the final registration of the radiopharmaceutical Luthatera® for G1/G2 NET patients in 2017, the long-term results of the phase 3 NETTER-2 trial may pave the way for a new treatment option also for advanced G2/G3 patients as first-line therapy. The growing knowledge about the synergistic effect of combined therapies could also allow alternative (re)treatment options for NET patients, in order to create a tailored treatment strategy. The evolving thera(g)nostic concept could be applied for the identification of patients who might benefit from different image-guided treatment strategies. In this scenario, the use of dual tracer PET/CT in NET patients, using both [F]F-FDG/[Ga]Ga-DOTA-somatostatin analog (SSA) for diagnosis and follow-up, is under discussion and could also result in a powerful prognostic tool. In addition, alternative strategies based on different metabolic pathways, radioisotopes, or combinations of different medical approaches could be applied. A number of different promising "doors" could thus open in the near future for the treatment of NET patients - and the "key" will be thera(g)nostic!
Theranostics in Neurooncology: Heading Toward New Horizons
Tolboom N, Verger A, Albert NL, Fraioli F, Guedj E, Traub-Weidinger T, Morbelli S, Herrmann K, Zucchetta P, Plasschaert SLA, Yakushev I, Weller M, Glas M, Preusser M, Cecchin D, Barthel H and Van Weehaeghe D
Theranostics in Neurooncology: Heading Toward New Horizons
Tolboom N, Verger A, Albert NL, Fraioli F, Guedj E, Traub-Weidinger T, Morbelli S, Herrmann K, Zucchetta P, Plasschaert SLA, Yakushev I, Weller M, Glas M, Preusser M, Cecchin D, Barthel H and Van Weehaeghe D
Therapeutic approaches to brain tumors remain a challenge, with considerable limitations regarding delivery of drugs. There has been renewed and increasing interest in translating the popular theranostic approach well known from prostate and neuroendocrine cancer to neurooncology. Although far from perfect, some of these approaches show encouraging preliminary results, such as for meningioma and leptomeningeal spread of certain pediatric brain tumors. In brain metastases and gliomas, clinical results have failed to impress. Perspectives on these theranostic approaches regarding meningiomas, brain metastases, gliomas, and common pediatric brain tumors will be discussed. For each tumor entity, the general context, an overview of the literature, and future perspectives will be provided. Ongoing studies will be discussed in the supplemental materials. As most theranostic agents are unlikely to cross the blood-brain barrier, the delivery of these agents will be dependent on the successful development and clinical implementation of techniques enhancing permeability and retention. Moreover, the international community should strive toward sufficiently large and randomized studies to generate high-level evidence on theranostic approaches with radioligand therapies for central nervous system tumors.
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.
Radiobiological Assessment of Targeted Radionuclide Therapy with [Lu]Lu-PSMA-I&T in 2D vs. 3D Cell Culture Models
Raitanen J, Barta B, Fuchs H, Hacker M, Balber T, Georg D and Mitterhauser M
Radiobiological Assessment of Targeted Radionuclide Therapy with [Lu]Lu-PSMA-I&T in 2D vs. 3D Cell Culture Models
Raitanen J, Barta B, Fuchs H, Hacker M, Balber T, Georg D and Mitterhauser M
In vitro therapeutic efficacy studies are commonly conducted in cell monolayers. However, three-dimensional (3D) tumor spheroids are known to better represent in vivo tumors. This study used [Lu]Lu-PSMA-I&T, an already clinically applied radiopharmaceutical for targeted radionuclide therapy against metastatic castrate-resistant prostate cancer, to demonstrate the differences in the radiobiological response between 2D and 3D cell culture models of the prostate cancer cell lines PC-3 (PSMA negative) and LNCaP (PSMA positive). After assessing the target expression in both models via Western Blot, cell viability, reproductive ability, and growth inhibition were assessed. To investigate the geometric effects on dosimetry for the 2D vs. 3D models, Monte Carlo simulations were performed. Our results showed that PSMA expression in LNCaP spheroids was highly preserved, and target specificity was shown in both models. In monolayers of LNCaP, no short-term (48 h after treatment), but only long-term (14 days after treatment) radiobiological effects were evident, showing decreased viability and reproductive ability with the increasing activity. Further, LNCaP spheroid growth was inhibited with the increasing activity. Overall, treatment efficacy was higher in LNCaP spheroids compared to monolayers, which can be explained by the difference in the resulting dose, among others.
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.
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.
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.
Peptide receptor radionuclide therapy combinations for neuroendocrine tumours in ongoing clinical trials: status 2023
di Santo G, Santo G, Sviridenko A and Virgolini I
Peptide receptor radionuclide therapy combinations for neuroendocrine tumours in ongoing clinical trials: status 2023
di Santo G, Santo G, Sviridenko A and Virgolini I
A growing body of literature reports on the combined use of peptide receptor radionuclide therapy (PRRT) with other anti-tumuor therapies in order to anticipate synergistic effects with perhaps increased safety issues. Combination treatments to enhance PRRT outcome are based on improved tumour perfusion, upregulation of somatostatin receptors (SSTR), radiosensitization with DNA damaging agents or targeted therapies. Several Phase 1 or 2 trials are currently recruiting patients in combined regimens. The combination of PRRT with cytotoxic chemotherapy, capecitabine and temozolomide (CAPTEM), seems to become clinically useful especially in pancreatic neuroendocrine tumours (pNETs) with acceptable safety profile. Neoadjuvant PRRT prior to surgery, PRRT combinations of intravenous and intraarterial routes of application, combinations of PRRT with differently radiolabelled (alpha, beta, Auger) SSTR-targeting agonists and antagonists, inhibitors of immune checkpoints (ICIs), poly (ADP-ribose) polymerase-1 (PARP1i), tyrosine kinase (TKI), DNA-dependent protein kinase, ribonucleotide reductase or DNA methyltransferase (DMNT) are tested in currently ongoing clinical trials. The combination with [I]I-MIBG in rare NETs (such as paraganglioma, pheochromocytoma) and new non-SSTR-targeting radioligands are used in the personalization process of treatment. The present review will provide an overview of the current status of ongoing PRRT combination treatments.