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
FAPi PET/CT for assessment and visualisation of active myositis-related interstitial lung disease: a prospective observational pilot study
Kastrati K, Nakuz TS, Kulterer OC, Geßl I, Simader E, Mrak D, Bonelli M, Kiener HP, Prayer F, Prosch H, Aletaha D, Langsteger W, Traub-Weidinger T, Blüml S, Lechner-Radner H, Hacker M and Mandl P
FAPi PET/CT for assessment and visualisation of active myositis-related interstitial lung disease: a prospective observational pilot study
Kastrati K, Nakuz TS, Kulterer OC, Geßl I, Simader E, Mrak D, Bonelli M, Kiener HP, Prayer F, Prosch H, Aletaha D, Langsteger W, Traub-Weidinger T, Blüml S, Lechner-Radner H, Hacker M and Mandl P
Interstitial lung disease (ILD) is a common manifestation of idiopathic inflammatory myopathies (IIM) and a substantial contributor to hospitalisation, increased morbidity, and mortality. In-vivo evidence of ongoing tissue remodelling in IIM-ILD is scarce. We aimed to evaluate fibroblast activation in lungs of IIM-patients and control individuals using ⁶⁸Ga-labelled inhibitor of Fibroblast-Activation-Protein (FAPi) based positronic emission tomography and computed tomography imaging (PET/CT).
Initial [18F]DCFPyL PET/CT in treatment-naïve prostate cancer: correlation with post-ADT PSA outcomes and recurrence
Li Y, Wang S, Zhao S, Zhao P, Huang S, Li K, Han S, Tian C, Li X, Shi B and Li X
Initial [18F]DCFPyL PET/CT in treatment-naïve prostate cancer: correlation with post-ADT PSA outcomes and recurrence
Li Y, Wang S, Zhao S, Zhao P, Huang S, Li K, Han S, Tian C, Li X, Shi B and Li X
Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) targeting tracers has emerged as a valuable diagnostic tool for prostate cancer (PCa), androgen deprivation therapy (ADT) stands as the cornerstone treatment for advanced PCa, yet forecasting the response to hormonal therapy poses a significant clinical hurdle.
Correction to: Multiparametric Analysis Combining DSC-MR Perfusion and [18F]FET-PET is Superior to a Single Parameter Approach for Differentiation of Progressive Glioma from Radiation Necrosis
Panholzer J, Malsiner-Walli G, Grün B, Kalev O, Sonnberger M and Pichler R
Correction to: Multiparametric Analysis Combining DSC-MR Perfusion and [18F]FET-PET is Superior to a Single Parameter Approach for Differentiation of Progressive Glioma from Radiation Necrosis
Panholzer J, Malsiner-Walli G, Grün B, Kalev O, Sonnberger M and Pichler R
Whole brain pattern of iron accumulation in REM sleep behavior disorder
Varga Z, Keller J, Robinson SD, Serranova T, Nepozitek J, Zogala D, Trnka J, Ruzicka E, Sonka K and Dusek P
Whole brain pattern of iron accumulation in REM sleep behavior disorder
Varga Z, Keller J, Robinson SD, Serranova T, Nepozitek J, Zogala D, Trnka J, Ruzicka E, Sonka K and Dusek P
Isolated REM sleep behavior disorder (iRBD) is an early stage of synucleinopathy with most patients progressing to Parkinson's disease (PD) or related conditions. Quantitative susceptibility mapping (QSM) in PD has identified pathological iron accumulation in the substantia nigra (SN) and variably also in basal ganglia and cortex. Analyzing whole-brain QSM across iRBD, PD, and healthy controls (HC) may help to ascertain the extent of neurodegeneration in prodromal synucleinopathy. 70 de novo PD patients, 70 iRBD patients, and 60 HCs underwent 3 T MRI. T1 and susceptibility-weighted images were acquired and processed to space standardized QSM. Voxel-based analyses of grey matter magnetic susceptibility differences comparing all groups were performed on the whole brain and upper brainstem levels with the statistical threshold set at family-wise error-corrected p-values <.05. Whole-brain analysis showed increased susceptibility in the bilateral fronto-parietal cortex of iRBD patients compared to both PD and HC. This was not associated with cortical thinning according to the cortical thickness analysis. Compared to iRBD, PD patients had increased susceptibility in the left amygdala and hippocampal region. Upper brainstem analysis revealed increased susceptibility within the bilateral SN for both PD and iRBD compared to HC; changes were located predominantly in nigrosome 1 in the former and nigrosome 2 in the latter group. In the iRBD group, abnormal dopamine transporter SPECT was associated with increased susceptibility in nigrosome 1. iRBD patients display greater fronto-parietal cortex involvement than incidental early-stage PD cohort indicating more widespread subclinical neuropathology. Dopaminergic degeneration in the substantia nigra is paralleled by susceptibility increase, mainly in nigrosome 1.
Extracting value from total-body PET/CT image data - the emerging role of artificial intelligence
Shiyam Sundar LK, Gutschmayer S, Maenle M and Beyer T
Extracting value from total-body PET/CT image data - the emerging role of artificial intelligence
Shiyam Sundar LK, Gutschmayer S, Maenle M and Beyer T
The evolution of Positron Emission Tomography (PET), culminating in the Total-Body PET (TB-PET) system, represents a paradigm shift in medical imaging. This paper explores the transformative role of Artificial Intelligence (AI) in enhancing clinical and research applications of TB-PET imaging. Clinically, TB-PET's superior sensitivity facilitates rapid imaging, low-dose imaging protocols, improved diagnostic capabilities and higher patient comfort. In research, TB-PET shows promise in studying systemic interactions and enhancing our understanding of human physiology and pathophysiology. In parallel, AI's integration into PET imaging workflows-spanning from image acquisition to data analysis-marks a significant development in nuclear medicine. This review delves into the current and potential roles of AI in augmenting TB-PET/CT's functionality and utility. We explore how AI can streamline current PET imaging processes and pioneer new applications, thereby maximising the technology's capabilities. The discussion also addresses necessary steps and considerations for effectively integrating AI into TB-PET/CT research and clinical practice. The paper highlights AI's role in enhancing TB-PET's efficiency and addresses the challenges posed by TB-PET's increased complexity. In conclusion, this exploration emphasises the need for a collaborative approach in the field of medical imaging. We advocate for shared resources and open-source initiatives as crucial steps towards harnessing the full potential of the AI/TB-PET synergy. This collaborative effort is essential for revolutionising medical imaging, ultimately leading to significant advancements in patient care and medical research.
18F-FDG PET/CT in assessment of paraneoplastic cerebellar degeneration as the first sign of occult fallopian tube serous cystadenocarcinoma: Case report
Kalantari F, Schweighofer-Zwink G, Hecht S, Rendl G, Pirich C and Beheshti M
PET/CT in leukemia: utility and future directions
Al-Ibraheem A, Allouzi S, Abdlkadir AS, Mikhail-Lette M, Al-Rabi K, Ma'koseh M, Knoll P, Abdelrhman Z, Shahin O, Juweid ME, Paez D and Lopci E
PET/CT in leukemia: utility and future directions
Al-Ibraheem A, Allouzi S, Abdlkadir AS, Mikhail-Lette M, Al-Rabi K, Ma'koseh M, Knoll P, Abdelrhman Z, Shahin O, Juweid ME, Paez D and Lopci E
2-Deoxy-2-[18F]fluoro-d-glucose PET/computed tomography ([18F]FDG PET/CT) has proven to be a sensitive method for the detection and evaluation of hematologic malignancies, especially lymphoma. The increasing incidence and mortality rates of leukemia have raised significant concerns. Through the utilization of whole-body imaging, [18F]FDG PET/CT provides a thorough assessment of the entire bone marrow, complementing the limited insights provided by biopsy samples. In this regard, [18F]FDG PET/CT has the ability to assess diverse types of leukemia The utilization of [18F]FDG PET/CT has been found to be effective in evaluating leukemia spread beyond the bone marrow, tracking disease relapse, identifying Richter's transformation, and assessing the inflammatory activity associated with acute graft versus host disease. However, its role in various clinical scenarios in leukemia remains unacknowledged. Despite their less common use, some novel PET/CT radiotracers are being researched for potential use in specific scenarios in leukemia patients. Therefore, the objectives of this review are to provide a thorough assessment of the current applications of [18F]FDG PET/CT in the staging and monitoring of leukemia patients, as well as the potential for an expanding role of PET/CT in leukemia patients.
Conventional and novel [F]FDG PET/CT features as predictors of CAR-T cell therapy outcome in large B-cell lymphoma
Leithner D, Flynn JR, Devlin SM, Mauguen A, Fei T, Zeng S, Zheng J, Imber BS, Hubbeling H, Mayerhoefer ME, Bedmutha A, Luttwak E, Corona M, Dahi PB, Luna de Abia A, Landego I, Lin RJ, Palomba ML, Scordo M, Park JH, Tomas AA, Salles G, Lafontaine D, Michaud L, Shah GL, Perales MA, Shouval R and Schöder H
Conventional and novel [F]FDG PET/CT features as predictors of CAR-T cell therapy outcome in large B-cell lymphoma
Leithner D, Flynn JR, Devlin SM, Mauguen A, Fei T, Zeng S, Zheng J, Imber BS, Hubbeling H, Mayerhoefer ME, Bedmutha A, Luttwak E, Corona M, Dahi PB, Luna de Abia A, Landego I, Lin RJ, Palomba ML, Scordo M, Park JH, Tomas AA, Salles G, Lafontaine D, Michaud L, Shah GL, Perales MA, Shouval R and Schöder H
Relapse and toxicity limit the effectiveness of chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphoma (LBCL), yet biomarkers that predict outcomes and toxicity are lacking. We examined radiomic features extracted from pre-CAR-T F-fluorodeoxyglucose positron emission tomography/computed tomography ([F]FDG PET/CT) scans (n = 341) of 180 patients (121 male; median age, 66 years). Three conventional (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and 116 novel radiomic features were assessed, along with inflammatory markers, toxicities, and outcomes. At both pre-apheresis and pre-infusion time points, conventional PET features of disease correlated with elevated inflammatory markers. At pre-infusion, MTV was associated with grade ≥ 2 cytokine release syndrome (odds ratio [OR] for 100 mL increase: 1.08 [95% confidence interval (CI), 1.01-1.20], P = 0.031), and SUVmax was associated with failure to achieve complete response (CR) (OR 1.72 [95% CI, 1.24-2.43], P < 0.001). Higher pre-apheresis and pre-infusion MTV values were associated with shorter progression-free survival (PFS) (HR for 10-unit increase: 1.11 [95% CI, 1.05-1.17], P < 0.001; 1.04 [95% CI, 1.02-1.07], P < 0.001) and shorter overall survival (HR for 100-unit increase: 1.14 [95% CI, 1.07-1.21], P < 0.001; 1.04 [95% CI, 1.02-1.06], P < 0.001). A combined MTV and LDH measure stratified patients into high and low PFS risk groups. Multiple pre-infusion novel radiomic features were associated with CR. These quantitative conventional [F]FDG PET/CT features obtained before CAR-T cell infusion, which were correlated with inflammation markers, may provide prognostic biomarkers for CAR-T therapy efficacy and toxicity. The use of conventional and novel radiomic features may thus help identify high-risk patients for earlier interventions.
Complete Resolution of Locally Advanced Prostate Cancer After Molecular Endoradiotherapy With 177Lu-PSMA
Beheshti M, Vali R, Zarehparvar Moghadam S, Amini H, Hakiminejad M and Divband G
Complete Resolution of Locally Advanced Prostate Cancer After Molecular Endoradiotherapy With 177Lu-PSMA
Beheshti M, Vali R, Zarehparvar Moghadam S, Amini H, Hakiminejad M and Divband G
A 76-year-old man with castration-resistant prostate cancer underwent 68Ga-prostate-specific membrane antigen (PSMA) PET/CT for restaging. A large PSMA-avid tumor with invasion to adjacent organs was noted causing gross hematuria and symptomatic anemia. Two cycles of 177Lu-PSMA were administered, and the patient showed significant reduction of hematuria as well as declining in PSA levels. 177Lu-PSMA therapy can be a good treatment option in patients with locally invasive tumors.
Amide-to-Triazole Switch in Somatostatin-14-Based Radioligands: Impact on Receptor Affinity and In Vivo Stability
Guarrochena X, Kanellopoulos P, Stingeder A, Rečnik LM, Feiner IVJ, Brandt M, Kandioller W, Maina T, Nock BA and Mindt TL
Amide-to-Triazole Switch in Somatostatin-14-Based Radioligands: Impact on Receptor Affinity and In Vivo Stability
Guarrochena X, Kanellopoulos P, Stingeder A, Rečnik LM, Feiner IVJ, Brandt M, Kandioller W, Maina T, Nock BA and Mindt TL
The use of metabolically stabilized, radiolabeled somatostatin (SST) analogs ([Ga]Ga/[Lu]Lu-DOTA-TATE/TOC/NOC) is well established in nuclear medicine. Despite the pivotal role of these radioligands in the diagnosis and therapy of neuroendocrine tumors (NETs), their inability to interact with all five somatostatin receptors (SSTR) limits their clinical potential. [In]In-AT2S is a radiolabeled DOTA-conjugate derived from the parent peptide SST-14 that exhibits high binding affinity to all SSTR subtypes, but its poor metabolic stability represents a serious disadvantage for clinical use. In order to address this issue, we have replaced strategic -amide bonds of [In]In-AT2S with metabolically stable 1,4-disubstituted 1,2,3-triazole bioisosteres. From the five cyclic triazolo-peptidomimetics investigated, only [In]In-XG1 combined a preserved nanomolar affinity for the SSTR subtypes in vitro and an improved stability in vivo (up to 17% of intact peptide 5 min postinjection (pi) versus 6% for [In]In-AT2S). The involvement of neprilysin (NEP) in the metabolism of [In]In-XG1 was confirmed by coadministration of Entresto, a registered antihypertensive drug, in vivo releasing the selective and potent NEP-inhibitor sacubitrilat. A pilot SPECT/CT imaging study conducted in mice bearing hSSTR-positive xenografts failed to visualize the xenografts due to the pronounced kidney uptake (>200% injected activity (IA)/g at 4 h pi), likely the result of the formation of cationic metabolites. To corroborate the imaging data, the tumors and the kidneys were excised and analyzed with a -counter. Even if receptor-specific tumor uptake for [In]In-XG1 could be confirmed (1.61% IA/g), further optimization is required to improve its pharmacokinetic properties for radiotracer development.
Teilbereich PET
FAPi PET/CT for assessment and visualisation of active myositis-related interstitial lung disease: a prospective observational pilot study
Kastrati K, Nakuz TS, Kulterer OC, Geßl I, Simader E, Mrak D, Bonelli M, Kiener HP, Prayer F, Prosch H, Aletaha D, Langsteger W, Traub-Weidinger T, Blüml S, Lechner-Radner H, Hacker M and Mandl P
FAPi PET/CT for assessment and visualisation of active myositis-related interstitial lung disease: a prospective observational pilot study
Kastrati K, Nakuz TS, Kulterer OC, Geßl I, Simader E, Mrak D, Bonelli M, Kiener HP, Prayer F, Prosch H, Aletaha D, Langsteger W, Traub-Weidinger T, Blüml S, Lechner-Radner H, Hacker M and Mandl P
Interstitial lung disease (ILD) is a common manifestation of idiopathic inflammatory myopathies (IIM) and a substantial contributor to hospitalisation, increased morbidity, and mortality. In-vivo evidence of ongoing tissue remodelling in IIM-ILD is scarce. We aimed to evaluate fibroblast activation in lungs of IIM-patients and control individuals using ⁶⁸Ga-labelled inhibitor of Fibroblast-Activation-Protein (FAPi) based positronic emission tomography and computed tomography imaging (PET/CT).
Initial [18F]DCFPyL PET/CT in treatment-naïve prostate cancer: correlation with post-ADT PSA outcomes and recurrence
Li Y, Wang S, Zhao S, Zhao P, Huang S, Li K, Han S, Tian C, Li X, Shi B and Li X
Initial [18F]DCFPyL PET/CT in treatment-naïve prostate cancer: correlation with post-ADT PSA outcomes and recurrence
Li Y, Wang S, Zhao S, Zhao P, Huang S, Li K, Han S, Tian C, Li X, Shi B and Li X
Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) targeting tracers has emerged as a valuable diagnostic tool for prostate cancer (PCa), androgen deprivation therapy (ADT) stands as the cornerstone treatment for advanced PCa, yet forecasting the response to hormonal therapy poses a significant clinical hurdle.
Correction to: Multiparametric Analysis Combining DSC-MR Perfusion and [18F]FET-PET is Superior to a Single Parameter Approach for Differentiation of Progressive Glioma from Radiation Necrosis
Panholzer J, Malsiner-Walli G, Grün B, Kalev O, Sonnberger M and Pichler R
Correction to: Multiparametric Analysis Combining DSC-MR Perfusion and [18F]FET-PET is Superior to a Single Parameter Approach for Differentiation of Progressive Glioma from Radiation Necrosis
Panholzer J, Malsiner-Walli G, Grün B, Kalev O, Sonnberger M and Pichler R
Extracting value from total-body PET/CT image data - the emerging role of artificial intelligence
Shiyam Sundar LK, Gutschmayer S, Maenle M and Beyer T
Extracting value from total-body PET/CT image data - the emerging role of artificial intelligence
Shiyam Sundar LK, Gutschmayer S, Maenle M and Beyer T
The evolution of Positron Emission Tomography (PET), culminating in the Total-Body PET (TB-PET) system, represents a paradigm shift in medical imaging. This paper explores the transformative role of Artificial Intelligence (AI) in enhancing clinical and research applications of TB-PET imaging. Clinically, TB-PET's superior sensitivity facilitates rapid imaging, low-dose imaging protocols, improved diagnostic capabilities and higher patient comfort. In research, TB-PET shows promise in studying systemic interactions and enhancing our understanding of human physiology and pathophysiology. In parallel, AI's integration into PET imaging workflows-spanning from image acquisition to data analysis-marks a significant development in nuclear medicine. This review delves into the current and potential roles of AI in augmenting TB-PET/CT's functionality and utility. We explore how AI can streamline current PET imaging processes and pioneer new applications, thereby maximising the technology's capabilities. The discussion also addresses necessary steps and considerations for effectively integrating AI into TB-PET/CT research and clinical practice. The paper highlights AI's role in enhancing TB-PET's efficiency and addresses the challenges posed by TB-PET's increased complexity. In conclusion, this exploration emphasises the need for a collaborative approach in the field of medical imaging. We advocate for shared resources and open-source initiatives as crucial steps towards harnessing the full potential of the AI/TB-PET synergy. This collaborative effort is essential for revolutionising medical imaging, ultimately leading to significant advancements in patient care and medical research.
18F-FDG PET/CT in assessment of paraneoplastic cerebellar degeneration as the first sign of occult fallopian tube serous cystadenocarcinoma: Case report
Kalantari F, Schweighofer-Zwink G, Hecht S, Rendl G, Pirich C and Beheshti M
PET/CT in leukemia: utility and future directions
Al-Ibraheem A, Allouzi S, Abdlkadir AS, Mikhail-Lette M, Al-Rabi K, Ma'koseh M, Knoll P, Abdelrhman Z, Shahin O, Juweid ME, Paez D and Lopci E
PET/CT in leukemia: utility and future directions
Al-Ibraheem A, Allouzi S, Abdlkadir AS, Mikhail-Lette M, Al-Rabi K, Ma'koseh M, Knoll P, Abdelrhman Z, Shahin O, Juweid ME, Paez D and Lopci E
2-Deoxy-2-[18F]fluoro-d-glucose PET/computed tomography ([18F]FDG PET/CT) has proven to be a sensitive method for the detection and evaluation of hematologic malignancies, especially lymphoma. The increasing incidence and mortality rates of leukemia have raised significant concerns. Through the utilization of whole-body imaging, [18F]FDG PET/CT provides a thorough assessment of the entire bone marrow, complementing the limited insights provided by biopsy samples. In this regard, [18F]FDG PET/CT has the ability to assess diverse types of leukemia The utilization of [18F]FDG PET/CT has been found to be effective in evaluating leukemia spread beyond the bone marrow, tracking disease relapse, identifying Richter's transformation, and assessing the inflammatory activity associated with acute graft versus host disease. However, its role in various clinical scenarios in leukemia remains unacknowledged. Despite their less common use, some novel PET/CT radiotracers are being researched for potential use in specific scenarios in leukemia patients. Therefore, the objectives of this review are to provide a thorough assessment of the current applications of [18F]FDG PET/CT in the staging and monitoring of leukemia patients, as well as the potential for an expanding role of PET/CT in leukemia patients.
Conventional and novel [F]FDG PET/CT features as predictors of CAR-T cell therapy outcome in large B-cell lymphoma
Leithner D, Flynn JR, Devlin SM, Mauguen A, Fei T, Zeng S, Zheng J, Imber BS, Hubbeling H, Mayerhoefer ME, Bedmutha A, Luttwak E, Corona M, Dahi PB, Luna de Abia A, Landego I, Lin RJ, Palomba ML, Scordo M, Park JH, Tomas AA, Salles G, Lafontaine D, Michaud L, Shah GL, Perales MA, Shouval R and Schöder H
Conventional and novel [F]FDG PET/CT features as predictors of CAR-T cell therapy outcome in large B-cell lymphoma
Leithner D, Flynn JR, Devlin SM, Mauguen A, Fei T, Zeng S, Zheng J, Imber BS, Hubbeling H, Mayerhoefer ME, Bedmutha A, Luttwak E, Corona M, Dahi PB, Luna de Abia A, Landego I, Lin RJ, Palomba ML, Scordo M, Park JH, Tomas AA, Salles G, Lafontaine D, Michaud L, Shah GL, Perales MA, Shouval R and Schöder H
Relapse and toxicity limit the effectiveness of chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphoma (LBCL), yet biomarkers that predict outcomes and toxicity are lacking. We examined radiomic features extracted from pre-CAR-T F-fluorodeoxyglucose positron emission tomography/computed tomography ([F]FDG PET/CT) scans (n = 341) of 180 patients (121 male; median age, 66 years). Three conventional (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and 116 novel radiomic features were assessed, along with inflammatory markers, toxicities, and outcomes. At both pre-apheresis and pre-infusion time points, conventional PET features of disease correlated with elevated inflammatory markers. At pre-infusion, MTV was associated with grade ≥ 2 cytokine release syndrome (odds ratio [OR] for 100 mL increase: 1.08 [95% confidence interval (CI), 1.01-1.20], P = 0.031), and SUVmax was associated with failure to achieve complete response (CR) (OR 1.72 [95% CI, 1.24-2.43], P < 0.001). Higher pre-apheresis and pre-infusion MTV values were associated with shorter progression-free survival (PFS) (HR for 10-unit increase: 1.11 [95% CI, 1.05-1.17], P < 0.001; 1.04 [95% CI, 1.02-1.07], P < 0.001) and shorter overall survival (HR for 100-unit increase: 1.14 [95% CI, 1.07-1.21], P < 0.001; 1.04 [95% CI, 1.02-1.06], P < 0.001). A combined MTV and LDH measure stratified patients into high and low PFS risk groups. Multiple pre-infusion novel radiomic features were associated with CR. These quantitative conventional [F]FDG PET/CT features obtained before CAR-T cell infusion, which were correlated with inflammation markers, may provide prognostic biomarkers for CAR-T therapy efficacy and toxicity. The use of conventional and novel radiomic features may thus help identify high-risk patients for earlier interventions.
Diagnostic imaging of the diabetic foot: an EANM evidence-based guidance
Lauri C, Noriega-Álvarez E, Chakravartty RM, Gheysens O, Glaudemans AWJM, Slart RHJA, Kwee TC, Lecouvet F, Panagiotidis E, Zhang-Yin J, Martinez JLL, Lipsky BA, Uccioli L and Signore A
Diagnostic imaging of the diabetic foot: an EANM evidence-based guidance
Lauri C, Noriega-Álvarez E, Chakravartty RM, Gheysens O, Glaudemans AWJM, Slart RHJA, Kwee TC, Lecouvet F, Panagiotidis E, Zhang-Yin J, Martinez JLL, Lipsky BA, Uccioli L and Signore A
Consensus on the choice of the most accurate imaging strategy in diabetic foot infective and non-infective complications is still lacking. This document provides evidence-based recommendations, aiming at defining which imaging modality should be preferred in different clinical settings.
Complete Resolution of Locally Advanced Prostate Cancer After Molecular Endoradiotherapy With 177Lu-PSMA
Beheshti M, Vali R, Zarehparvar Moghadam S, Amini H, Hakiminejad M and Divband G
Complete Resolution of Locally Advanced Prostate Cancer After Molecular Endoradiotherapy With 177Lu-PSMA
Beheshti M, Vali R, Zarehparvar Moghadam S, Amini H, Hakiminejad M and Divband G
A 76-year-old man with castration-resistant prostate cancer underwent 68Ga-prostate-specific membrane antigen (PSMA) PET/CT for restaging. A large PSMA-avid tumor with invasion to adjacent organs was noted causing gross hematuria and symptomatic anemia. Two cycles of 177Lu-PSMA were administered, and the patient showed significant reduction of hematuria as well as declining in PSA levels. 177Lu-PSMA therapy can be a good treatment option in patients with locally invasive tumors.
Directional electrodes in deep brain stimulation: Results of a survey by the European Association of Neurosurgical Societies (EANS)
Krauss P, Duarte-Batista P, Hart MG, Avecillas-Chasin JM, Bercu MM, Hvingelby V, Massey F, Ackermans L, Kubben PL, van der Gaag NA, Krüger MT and
Directional electrodes in deep brain stimulation: Results of a survey by the European Association of Neurosurgical Societies (EANS)
Krauss P, Duarte-Batista P, Hart MG, Avecillas-Chasin JM, Bercu MM, Hvingelby V, Massey F, Ackermans L, Kubben PL, van der Gaag NA, Krüger MT and
Directional Leads (dLeads) represent a new technical tool in Deep Brain Stimulation (DBS), and a rapidly growing population of patients receive dLeads.
Teilbereich SPECT
Whole brain pattern of iron accumulation in REM sleep behavior disorder
Varga Z, Keller J, Robinson SD, Serranova T, Nepozitek J, Zogala D, Trnka J, Ruzicka E, Sonka K and Dusek P
Whole brain pattern of iron accumulation in REM sleep behavior disorder
Varga Z, Keller J, Robinson SD, Serranova T, Nepozitek J, Zogala D, Trnka J, Ruzicka E, Sonka K and Dusek P
Isolated REM sleep behavior disorder (iRBD) is an early stage of synucleinopathy with most patients progressing to Parkinson's disease (PD) or related conditions. Quantitative susceptibility mapping (QSM) in PD has identified pathological iron accumulation in the substantia nigra (SN) and variably also in basal ganglia and cortex. Analyzing whole-brain QSM across iRBD, PD, and healthy controls (HC) may help to ascertain the extent of neurodegeneration in prodromal synucleinopathy. 70 de novo PD patients, 70 iRBD patients, and 60 HCs underwent 3 T MRI. T1 and susceptibility-weighted images were acquired and processed to space standardized QSM. Voxel-based analyses of grey matter magnetic susceptibility differences comparing all groups were performed on the whole brain and upper brainstem levels with the statistical threshold set at family-wise error-corrected p-values <.05. Whole-brain analysis showed increased susceptibility in the bilateral fronto-parietal cortex of iRBD patients compared to both PD and HC. This was not associated with cortical thinning according to the cortical thickness analysis. Compared to iRBD, PD patients had increased susceptibility in the left amygdala and hippocampal region. Upper brainstem analysis revealed increased susceptibility within the bilateral SN for both PD and iRBD compared to HC; changes were located predominantly in nigrosome 1 in the former and nigrosome 2 in the latter group. In the iRBD group, abnormal dopamine transporter SPECT was associated with increased susceptibility in nigrosome 1. iRBD patients display greater fronto-parietal cortex involvement than incidental early-stage PD cohort indicating more widespread subclinical neuropathology. Dopaminergic degeneration in the substantia nigra is paralleled by susceptibility increase, mainly in nigrosome 1.
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.
Diagnostic imaging of the diabetic foot: an EANM evidence-based guidance
Lauri C, Noriega-Álvarez E, Chakravartty RM, Gheysens O, Glaudemans AWJM, Slart RHJA, Kwee TC, Lecouvet F, Panagiotidis E, Zhang-Yin J, Martinez JLL, Lipsky BA, Uccioli L and Signore A
Diagnostic imaging of the diabetic foot: an EANM evidence-based guidance
Lauri C, Noriega-Álvarez E, Chakravartty RM, Gheysens O, Glaudemans AWJM, Slart RHJA, Kwee TC, Lecouvet F, Panagiotidis E, Zhang-Yin J, Martinez JLL, Lipsky BA, Uccioli L and Signore A
Consensus on the choice of the most accurate imaging strategy in diabetic foot infective and non-infective complications is still lacking. This document provides evidence-based recommendations, aiming at defining which imaging modality should be preferred in different clinical settings.
Amide-to-Triazole Switch in Somatostatin-14-Based Radioligands: Impact on Receptor Affinity and In Vivo Stability
Guarrochena X, Kanellopoulos P, Stingeder A, Rečnik LM, Feiner IVJ, Brandt M, Kandioller W, Maina T, Nock BA and Mindt TL
Amide-to-Triazole Switch in Somatostatin-14-Based Radioligands: Impact on Receptor Affinity and In Vivo Stability
Guarrochena X, Kanellopoulos P, Stingeder A, Rečnik LM, Feiner IVJ, Brandt M, Kandioller W, Maina T, Nock BA and Mindt TL
The use of metabolically stabilized, radiolabeled somatostatin (SST) analogs ([Ga]Ga/[Lu]Lu-DOTA-TATE/TOC/NOC) is well established in nuclear medicine. Despite the pivotal role of these radioligands in the diagnosis and therapy of neuroendocrine tumors (NETs), their inability to interact with all five somatostatin receptors (SSTR) limits their clinical potential. [In]In-AT2S is a radiolabeled DOTA-conjugate derived from the parent peptide SST-14 that exhibits high binding affinity to all SSTR subtypes, but its poor metabolic stability represents a serious disadvantage for clinical use. In order to address this issue, we have replaced strategic -amide bonds of [In]In-AT2S with metabolically stable 1,4-disubstituted 1,2,3-triazole bioisosteres. From the five cyclic triazolo-peptidomimetics investigated, only [In]In-XG1 combined a preserved nanomolar affinity for the SSTR subtypes in vitro and an improved stability in vivo (up to 17% of intact peptide 5 min postinjection (pi) versus 6% for [In]In-AT2S). The involvement of neprilysin (NEP) in the metabolism of [In]In-XG1 was confirmed by coadministration of Entresto, a registered antihypertensive drug, in vivo releasing the selective and potent NEP-inhibitor sacubitrilat. A pilot SPECT/CT imaging study conducted in mice bearing hSSTR-positive xenografts failed to visualize the xenografts due to the pronounced kidney uptake (>200% injected activity (IA)/g at 4 h pi), likely the result of the formation of cationic metabolites. To corroborate the imaging data, the tumors and the kidneys were excised and analyzed with a -counter. Even if receptor-specific tumor uptake for [In]In-XG1 could be confirmed (1.61% IA/g), further optimization is required to improve its pharmacokinetic properties for radiotracer development.
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.
A new method of modeling the multi-stage decision-making process of CRT using machine learning with uncertainty quantification
Larsen K, Zhao C, Keyak J, Sha Q, Paez D, Zhang X, Hung GU, Zou J, Peix A and Zhou W
A new method of modeling the multi-stage decision-making process of CRT using machine learning with uncertainty quantification
Larsen K, Zhao C, Keyak J, Sha Q, Paez D, Zhang X, Hung GU, Zou J, Peix A and Zhou W
Current machine learning-based (ML) models usually attempt to utilize all available patient data to predict patient outcomes while ignoring the associated cost and time for data acquisition. The purpose of this study is to create a multi-stage machine learning model to predict cardiac resynchronization therapy (CRT) response for heart failure (HF) patients. This model exploits uncertainty quantification to recommend additional collection of single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) variables if baseline clinical variables and features from electrocardiogram (ECG) are not sufficient.
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.
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!
Dosimetry and pharmacokinetics of [Lu]Lu-satoreotide tetraxetan in patients with progressive neuroendocrine tumours
Schürrle SB, Eberlein U, Ansquer C, Beauregard JM, Durand-Gasselin L, Grønbæk H, Haug A, Hicks RJ, Lenzo NP, Navalkissoor S, Nicolas GP, Pais B, Volteau M, Wild D, McEwan A and Lassmann M
Dosimetry and pharmacokinetics of [Lu]Lu-satoreotide tetraxetan in patients with progressive neuroendocrine tumours
Schürrle SB, Eberlein U, Ansquer C, Beauregard JM, Durand-Gasselin L, Grønbæk H, Haug A, Hicks RJ, Lenzo NP, Navalkissoor S, Nicolas GP, Pais B, Volteau M, Wild D, McEwan A and Lassmann M
To evaluate the dosimetry and pharmacokinetics of the novel radiolabelled somatostatin receptor antagonist [Lu]Lu-satoreotide tetraxetan in patients with advanced neuroendocrine tumours (NETs).
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.
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.
From biology to clinical practice: antiproliferative effects of somatostatin analogs in neuroendocrine neoplasms
Melhorn P, Mazal P, Wolff L, Kretschmer-Chott E, Raderer M and Kiesewetter B
From biology to clinical practice: antiproliferative effects of somatostatin analogs in neuroendocrine neoplasms
Melhorn P, Mazal P, Wolff L, Kretschmer-Chott E, Raderer M and Kiesewetter B
Somatostatin analogs (SSA), specifically octreotide and lanreotide, have demonstrated antiproliferative effects in patients with neuroendocrine tumors (NET), a group of rare malignancies of diverse origin and presentation. A prominent feature of NET cells is the expression of G protein-coupled receptors called somatostatin receptors (SSTR). Although these SSTR are not uniformly present in NET, they can be instrumental in the diagnosis and treatment of NET. Apart from their application in nuclear imaging and radionuclide therapy, SSA have proven invaluable in the treatment of hormonal syndromes associated with certain NET (antisecretory effects of SSA), but it took more than two decades to convincingly demonstrate the antiproliferative effects of SSA in metastatic NET with the two pivotal studies PROMID and CLARINET. The current review summarizes three decades of SSA treatment and provides an overview of the clinical trial landscape for SSA monotherapy and combination therapy, including clinical implications and quality of life aspects, as well as ongoing fields of research.