Pub Date : 2025-12-04DOI: 10.2967/jnumed.125.270117
Yunlai Chen,Robert A Mintzer,Sanghee Cho,Darren Pocci,Mahdjoub Hamdi,Sergey Komarov,Ling Cai,Samarth Aggarwal,Anthony Thomas,James Corbeil,Jennifer Frye,Farrokh Dehdashti,Joseph A O'Sullivan,Richard Laforest,Stefan B Siegel,Yuan-Chuan Tai
Augmented whole-body scanning via magnifying PET (AWSM-PET) is a technology that aims to enhance the image resolution and sensitivity of the clinical PET/CT scanner for whole-body imaging. This study presents the system design, performance evaluation, and results from phantoms and initial human imaging studies. Methods: The AWSM-PET system integrates 2 high-resolution detector panels ("outserts") with a Biograph Vision PET/CT scanner (Siemens Healthineers). Positioned outside the scanner's axial field of view, each panel consists of 32 detector modules, each containing a 30 × 30 lutetium oxyorthosilicate crystal array (0.97 × 0.97 × 10 mm³ per crystal) at 1.05-mm pitch. These detectors are packaged and read out using the scanner's detector electronics assembly. Customized firmware and software were developed to establish the additional coincidence detection among the outserts and the scanner. The system acquires data simultaneously during a whole-body scan using continuous bed motion. List-mode-based image reconstruction software has been developed for AWSM-PET system using the continuous-bed-motion protocol. Performance was evaluated through sensitivity measurements, imaging of a mini-resolution phantom containing multiple groups of hot spheres, a National Electrical Manufacturers Association Image Quality (NEMA IQ) phantom study with custom small-diameter tumor inserts, and an initial human study. Results: The outsert detectors achieved an energy resolution of 11% at 511 keV. The coincidence resolving time between the outserts and between outserts and scanner was 183 and 211 ps full width at half maximum, respectively. Sensitivity increased by up to 18.4%, depending on the source location. Mini-resolution phantom images demonstrated higher peak-to-valley ratios for spheres with a diameter of 6 mm or less compared with native scanner images. In the NEMA IQ study, AWSM-PET achieved a higher contrast recovery ratio (CRC) for the smallest spheric lesion (diameter, 4.88 mm) across all CRC metrics (maximum, peak, and mean) but no improvement for larger lesions compared with high-resolution Biograph Vision images. Initial human imaging confirmed the system's compatibility with clinical workflows, achieving improved resolution in high-count regions, such as the brain. However, increased noise in low-count regions (e.g., abdomen) was observed and requires further improvement. Conclusion: The prototype AWSM-PET system demonstrated enhanced image resolution and sensitivity of a clinical PET/CT scanner without negatively impacting its performance, showing improved CRC and spatial resolution for small lesions in phantom and human imaging.
{"title":"Development of a Prototype AWSM-PET Device for Augmented Whole-Body PET Imaging and Initial Human Study.","authors":"Yunlai Chen,Robert A Mintzer,Sanghee Cho,Darren Pocci,Mahdjoub Hamdi,Sergey Komarov,Ling Cai,Samarth Aggarwal,Anthony Thomas,James Corbeil,Jennifer Frye,Farrokh Dehdashti,Joseph A O'Sullivan,Richard Laforest,Stefan B Siegel,Yuan-Chuan Tai","doi":"10.2967/jnumed.125.270117","DOIUrl":"https://doi.org/10.2967/jnumed.125.270117","url":null,"abstract":"Augmented whole-body scanning via magnifying PET (AWSM-PET) is a technology that aims to enhance the image resolution and sensitivity of the clinical PET/CT scanner for whole-body imaging. This study presents the system design, performance evaluation, and results from phantoms and initial human imaging studies. Methods: The AWSM-PET system integrates 2 high-resolution detector panels (\"outserts\") with a Biograph Vision PET/CT scanner (Siemens Healthineers). Positioned outside the scanner's axial field of view, each panel consists of 32 detector modules, each containing a 30 × 30 lutetium oxyorthosilicate crystal array (0.97 × 0.97 × 10 mm³ per crystal) at 1.05-mm pitch. These detectors are packaged and read out using the scanner's detector electronics assembly. Customized firmware and software were developed to establish the additional coincidence detection among the outserts and the scanner. The system acquires data simultaneously during a whole-body scan using continuous bed motion. List-mode-based image reconstruction software has been developed for AWSM-PET system using the continuous-bed-motion protocol. Performance was evaluated through sensitivity measurements, imaging of a mini-resolution phantom containing multiple groups of hot spheres, a National Electrical Manufacturers Association Image Quality (NEMA IQ) phantom study with custom small-diameter tumor inserts, and an initial human study. Results: The outsert detectors achieved an energy resolution of 11% at 511 keV. The coincidence resolving time between the outserts and between outserts and scanner was 183 and 211 ps full width at half maximum, respectively. Sensitivity increased by up to 18.4%, depending on the source location. Mini-resolution phantom images demonstrated higher peak-to-valley ratios for spheres with a diameter of 6 mm or less compared with native scanner images. In the NEMA IQ study, AWSM-PET achieved a higher contrast recovery ratio (CRC) for the smallest spheric lesion (diameter, 4.88 mm) across all CRC metrics (maximum, peak, and mean) but no improvement for larger lesions compared with high-resolution Biograph Vision images. Initial human imaging confirmed the system's compatibility with clinical workflows, achieving improved resolution in high-count regions, such as the brain. However, increased noise in low-count regions (e.g., abdomen) was observed and requires further improvement. Conclusion: The prototype AWSM-PET system demonstrated enhanced image resolution and sensitivity of a clinical PET/CT scanner without negatively impacting its performance, showing improved CRC and spatial resolution for small lesions in phantom and human imaging.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04DOI: 10.2967/jnumed.125.270916
Vishnu Murthy,Koichiro Kimura,Lela Theus,Andrew Nguyen,Tristan R Grogan,Ojaswita Lokre,Timothy Perk,Matthew B Rettig,Alexandra Drakaki,John Shen,Pan Thin,Kathleen Nguyen,Stephanie Lira,Rejah Marie Nabong,Linda Gardner,Brian D Gonzalez,Andrei Gafita,Johannes Czernin,Jeremie Calais
This study aimed to investigate whether quantitative parameters derived from baseline prostate-specific membrane antigen (PSMA) PET imaging can predict hematologic toxicity and patient-reported outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with 177Lu-PSMA-617. Methods: This retrospective study analyzed data from the U.S. expanded-access program at UCLA (NCT04825652). We included 61 patients with mCRPC who received 177Lu-PSMA-617 between May 2021 and March 2022 and had available baseline PSMA PET scans, hematologic toxicity data, and patient-reported outcomes. Questionnaires included the Functional Assessment of Cancer Therapy-Prostate (FACT-P), the Brief Pain Inventory-Short Form (BPI-SF), and a xerostomia assessment, all completed at each treatment cycle. Baseline PSMA PET parameters-including volume, SUVmean, SUVmax, and total lesion PSMA (TLP; calculated by multiplying SUVmean by volume) for whole-body disease, bone disease, and salivary glands-were quantified using TRAQinform IQ. Associations between these imaging metrics and clinical outcomes were assessed using univariate and multivariate models. Results: Multivariate Cox regression analysis showed that higher baseline bone tumor SUVmean was significantly associated with delayed onset of grade 3 or 4 hematologic toxicity (hazard ratio [HR], 0.59; 95% CI, 0.36-0.98; P = 0.040), suggesting a protective effect. Conversely, higher bone TLP was associated with earlier onset of severe toxicity (HR, 1.31; 95% CI, 1.00-1.71; P = 0.049). Elevated whole-body SUVmean at baseline was predictive of delayed deterioration in both FACT-P total scores (HR, 0.59; 95% CI, 0.43-0.83; P = 0.002) and BPI-SF pain intensity (HR, 0.66; 95% CI, 0.46-0.93; P = 0.019). Additionally, higher salivary gland SUVmean, SUVmax, and TLP were significantly associated with increased xerostomia severity (P = 0.002, P = 0.006, and P = 0.015, respectively) in multivariate linear mixed-effects modeling. Conclusion: In this retrospective analysis of patients with mCRPC treated with 177Lu-PSMA-617, baseline quantitative PSMA PET parameters were associated with both treatment-related toxicities and patient-reported outcomes. Validation in a larger, prospective, multicenter cohort is warranted.
{"title":"Linking Baseline PSMA PET-Derived Parameters to Toxicity, Adverse Events, Pain, and Quality of Life in Patients Treated with [177Lu]Lu-PSMA-617: A Single-Center Retrospective Study.","authors":"Vishnu Murthy,Koichiro Kimura,Lela Theus,Andrew Nguyen,Tristan R Grogan,Ojaswita Lokre,Timothy Perk,Matthew B Rettig,Alexandra Drakaki,John Shen,Pan Thin,Kathleen Nguyen,Stephanie Lira,Rejah Marie Nabong,Linda Gardner,Brian D Gonzalez,Andrei Gafita,Johannes Czernin,Jeremie Calais","doi":"10.2967/jnumed.125.270916","DOIUrl":"https://doi.org/10.2967/jnumed.125.270916","url":null,"abstract":"This study aimed to investigate whether quantitative parameters derived from baseline prostate-specific membrane antigen (PSMA) PET imaging can predict hematologic toxicity and patient-reported outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with 177Lu-PSMA-617. Methods: This retrospective study analyzed data from the U.S. expanded-access program at UCLA (NCT04825652). We included 61 patients with mCRPC who received 177Lu-PSMA-617 between May 2021 and March 2022 and had available baseline PSMA PET scans, hematologic toxicity data, and patient-reported outcomes. Questionnaires included the Functional Assessment of Cancer Therapy-Prostate (FACT-P), the Brief Pain Inventory-Short Form (BPI-SF), and a xerostomia assessment, all completed at each treatment cycle. Baseline PSMA PET parameters-including volume, SUVmean, SUVmax, and total lesion PSMA (TLP; calculated by multiplying SUVmean by volume) for whole-body disease, bone disease, and salivary glands-were quantified using TRAQinform IQ. Associations between these imaging metrics and clinical outcomes were assessed using univariate and multivariate models. Results: Multivariate Cox regression analysis showed that higher baseline bone tumor SUVmean was significantly associated with delayed onset of grade 3 or 4 hematologic toxicity (hazard ratio [HR], 0.59; 95% CI, 0.36-0.98; P = 0.040), suggesting a protective effect. Conversely, higher bone TLP was associated with earlier onset of severe toxicity (HR, 1.31; 95% CI, 1.00-1.71; P = 0.049). Elevated whole-body SUVmean at baseline was predictive of delayed deterioration in both FACT-P total scores (HR, 0.59; 95% CI, 0.43-0.83; P = 0.002) and BPI-SF pain intensity (HR, 0.66; 95% CI, 0.46-0.93; P = 0.019). Additionally, higher salivary gland SUVmean, SUVmax, and TLP were significantly associated with increased xerostomia severity (P = 0.002, P = 0.006, and P = 0.015, respectively) in multivariate linear mixed-effects modeling. Conclusion: In this retrospective analysis of patients with mCRPC treated with 177Lu-PSMA-617, baseline quantitative PSMA PET parameters were associated with both treatment-related toxicities and patient-reported outcomes. Validation in a larger, prospective, multicenter cohort is warranted.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04DOI: 10.2967/jnumed.125.270802
Iris Schmidt,Pia Volkmer,Rogier P H M Müskens,Anne M van der Waaij,Gooitzen M van Dam,E Angela Huiskamp,Wouter B Nagengast
The purpose of this study was to determine the safety and feasibility of fluorescence molecular imaging using a commercially available system and intravenous injection of fluorescently labeled bevacizumab (bevacizumab-800CW) to visualize bevacizumab distribution in patients with neovascular age-related macular degeneration (nAMD)s. Methods: Twelve patients with active nAMD aged 60 y or older, who were either on anti-vascular endothelial growth factor (VEGF) therapy or were anti-VEGF therapy naïve, received an intravenous injection of 4.5 mg (n = 3) or 15 mg (n = 9) of bevacizumab-800CW. This clinical trial was divided into 2 parts. An interim analysis was performed after the inclusion of 3 patients per dose group (study part 1) to determine the more optimal dose. Then 6 additional patients were included with the optimal dose in study part 2. All patients underwent standard clinical imaging, including fundus photography, optical coherence tomography, optical coherence tomography angiography, and fluorescein angiography. Fluorescence imaging was performed 1 min, 60 min, and 3-4 d after bevacizumab-800CW injection. Results: Bevacizumab-800CW injections were safe and well tolerated. One minute after injection, only the 15-mg group demonstrated a significantly higher contrast-to-noise ratio (median, 6.32) in vessels compared with baseline (median, -4.44; P = 0.0342). This, combined with the clear visual uptake after 3-4 d, supported 15 mg as the preferred dose. Contrast-to-noise ratio values inside the macula of patients receiving 15 mg of bevacizumab-800CW (n = 8) were significantly higher after 3-4 d (median, 4.45) compared with baseline (median, 0.19; P = 0.0078). Conclusion: Targeted fluorescent tracers such as bevacizumab-800CW can visualize VEGF expression, providing important insights into nAMD, and can pave the way toward personalized treatments and targeted drug development.
{"title":"Targeted Fluorescence Imaging of Bevacizumab-800CW in Patients with Neovascular Age-Related Macular Degeneration.","authors":"Iris Schmidt,Pia Volkmer,Rogier P H M Müskens,Anne M van der Waaij,Gooitzen M van Dam,E Angela Huiskamp,Wouter B Nagengast","doi":"10.2967/jnumed.125.270802","DOIUrl":"https://doi.org/10.2967/jnumed.125.270802","url":null,"abstract":"The purpose of this study was to determine the safety and feasibility of fluorescence molecular imaging using a commercially available system and intravenous injection of fluorescently labeled bevacizumab (bevacizumab-800CW) to visualize bevacizumab distribution in patients with neovascular age-related macular degeneration (nAMD)s. Methods: Twelve patients with active nAMD aged 60 y or older, who were either on anti-vascular endothelial growth factor (VEGF) therapy or were anti-VEGF therapy naïve, received an intravenous injection of 4.5 mg (n = 3) or 15 mg (n = 9) of bevacizumab-800CW. This clinical trial was divided into 2 parts. An interim analysis was performed after the inclusion of 3 patients per dose group (study part 1) to determine the more optimal dose. Then 6 additional patients were included with the optimal dose in study part 2. All patients underwent standard clinical imaging, including fundus photography, optical coherence tomography, optical coherence tomography angiography, and fluorescein angiography. Fluorescence imaging was performed 1 min, 60 min, and 3-4 d after bevacizumab-800CW injection. Results: Bevacizumab-800CW injections were safe and well tolerated. One minute after injection, only the 15-mg group demonstrated a significantly higher contrast-to-noise ratio (median, 6.32) in vessels compared with baseline (median, -4.44; P = 0.0342). This, combined with the clear visual uptake after 3-4 d, supported 15 mg as the preferred dose. Contrast-to-noise ratio values inside the macula of patients receiving 15 mg of bevacizumab-800CW (n = 8) were significantly higher after 3-4 d (median, 4.45) compared with baseline (median, 0.19; P = 0.0078). Conclusion: Targeted fluorescent tracers such as bevacizumab-800CW can visualize VEGF expression, providing important insights into nAMD, and can pave the way toward personalized treatments and targeted drug development.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04DOI: 10.2967/jnumed.125.270411
Erik S Mittra,Lilja B Solnes,Astrid A M van der Veldt,Jeffrey Wong,Luigi Aloj,Michael C Heinrich,Christopher T Chen,Steven P Rowe,Tessa Brabander,Simon Pacey,Paola Aimone,Dhrubajyoti Pathak,Lars Blumenstein,Yongmin Liu,Andrei Iagaru
Gastrin-releasing peptide receptor (GRPR) is overexpressed in a range of tumor types, making it an attractive candidate for novel treatment approaches. NeoB binds to GRPR with high affinity and can be radiolabeled with 68Ga ([68Ga]Ga-NeoB) for imaging or 177Lu ([177Lu]Lu-NeoB, hereafter 177Lu-NeoB) for therapy, making it suitable for theranostics. Methods: NeoRay is a prospective, phase 1/2a, open-label, multicenter, first-in-human study of 177Lu-NeoB. Patients with selected advanced solid tumors with GRPR expression (confirmed by [68Ga]Ga-NeoB lesion uptake) were enrolled. Here, we report preliminary data (cutoff, April 29, 2024) from phase 1, which aimed to identify the maximum tolerated dose and/or recommended phase 2 dose of 177Lu-NeoB. Patients were scheduled to receive at least 3 cycles of 177Lu-NeoB at an interval of at least 6 wk. A Bayesian optimal interval design was used, with dose-escalation decisions based on dose-limiting toxicities (DLTs) during cycle 1 of each dose level. The primary endpoint was the incidence and nature of DLTs. Safety was assessed before and throughout each cycle. Dosimetry was assessed after the first administration. Results: Seventeen patients (median age, 65 y; 71% male) with advanced gastrointestinal stromal tumors, prostate cancer, glioblastoma, or breast cancer received 177Lu-NeoB activities of 1.85 GBq (cycle 1) and then 5.55 GBq (cycles 2-4) (n = 3), 9.25 GBq (n = 9), or 11.1 GBq (n = 5). Four DLTs were observed in 3 patients who received 11.1 GBq: grade 3 anemia (n = 2), grade 4 neurologic decline (n = 1), and grade 3 encephalopathy (n = 1). No DLTs were observed at lower administered activities. Overall, 4 of 17 patients (23.5%) had treatment-related adverse events of grade 3 or higher. Among patients with at least 1 evaluable dosimetry measurement (n = 16), the mean absorbed dose coefficient was 0.10 Gy/GBq (SD, 0.056 Gy/GBq) in the kidneys, 0.055 Gy/GBq (SD, 0.039 Gy/GBq) in the pancreas, and 0.018 Gy/GBq (SD, 0.0076 Gy/GBq) in the red marrow. Conclusion: 177Lu-NeoB has a favorable organ dosimetry profile in patients with advanced solid tumors expressing GRPR, with a large safety margin compared with accepted external beam radiation therapy thresholds for organ toxicity. The maximum tolerated dose of 177Lu-NeoB was identified as 9.25 GBq, and the recommended phase 2 dose for the phase 2a dose expansion is 9.25 GBq.
{"title":"Phase 1 Study of [177Lu]Lu-NeoB in Patients with Advanced Solid Tumors Overexpressing Gastrin-Releasing Peptide Receptor: Preliminary Safety and Dosimetry Results.","authors":"Erik S Mittra,Lilja B Solnes,Astrid A M van der Veldt,Jeffrey Wong,Luigi Aloj,Michael C Heinrich,Christopher T Chen,Steven P Rowe,Tessa Brabander,Simon Pacey,Paola Aimone,Dhrubajyoti Pathak,Lars Blumenstein,Yongmin Liu,Andrei Iagaru","doi":"10.2967/jnumed.125.270411","DOIUrl":"https://doi.org/10.2967/jnumed.125.270411","url":null,"abstract":"Gastrin-releasing peptide receptor (GRPR) is overexpressed in a range of tumor types, making it an attractive candidate for novel treatment approaches. NeoB binds to GRPR with high affinity and can be radiolabeled with 68Ga ([68Ga]Ga-NeoB) for imaging or 177Lu ([177Lu]Lu-NeoB, hereafter 177Lu-NeoB) for therapy, making it suitable for theranostics. Methods: NeoRay is a prospective, phase 1/2a, open-label, multicenter, first-in-human study of 177Lu-NeoB. Patients with selected advanced solid tumors with GRPR expression (confirmed by [68Ga]Ga-NeoB lesion uptake) were enrolled. Here, we report preliminary data (cutoff, April 29, 2024) from phase 1, which aimed to identify the maximum tolerated dose and/or recommended phase 2 dose of 177Lu-NeoB. Patients were scheduled to receive at least 3 cycles of 177Lu-NeoB at an interval of at least 6 wk. A Bayesian optimal interval design was used, with dose-escalation decisions based on dose-limiting toxicities (DLTs) during cycle 1 of each dose level. The primary endpoint was the incidence and nature of DLTs. Safety was assessed before and throughout each cycle. Dosimetry was assessed after the first administration. Results: Seventeen patients (median age, 65 y; 71% male) with advanced gastrointestinal stromal tumors, prostate cancer, glioblastoma, or breast cancer received 177Lu-NeoB activities of 1.85 GBq (cycle 1) and then 5.55 GBq (cycles 2-4) (n = 3), 9.25 GBq (n = 9), or 11.1 GBq (n = 5). Four DLTs were observed in 3 patients who received 11.1 GBq: grade 3 anemia (n = 2), grade 4 neurologic decline (n = 1), and grade 3 encephalopathy (n = 1). No DLTs were observed at lower administered activities. Overall, 4 of 17 patients (23.5%) had treatment-related adverse events of grade 3 or higher. Among patients with at least 1 evaluable dosimetry measurement (n = 16), the mean absorbed dose coefficient was 0.10 Gy/GBq (SD, 0.056 Gy/GBq) in the kidneys, 0.055 Gy/GBq (SD, 0.039 Gy/GBq) in the pancreas, and 0.018 Gy/GBq (SD, 0.0076 Gy/GBq) in the red marrow. Conclusion: 177Lu-NeoB has a favorable organ dosimetry profile in patients with advanced solid tumors expressing GRPR, with a large safety margin compared with accepted external beam radiation therapy thresholds for organ toxicity. The maximum tolerated dose of 177Lu-NeoB was identified as 9.25 GBq, and the recommended phase 2 dose for the phase 2a dose expansion is 9.25 GBq.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04DOI: 10.2967/jnumed.125.271318
Alexander Maurer,Urs J Muehlematter,Thibika Sivakumar,Ashkan Mortezavi,Jakob Heimer,Basil Kaufmann,Stephan Beintner-Skawran,Michael Messerli,Martin W Huellner,Daniel Eberli,Irene A Burger
High-intensity focused ultrasound (HIFU) is an increasingly used, locally ablative therapy option in localized prostate cancer (PCa). Multiparametric MRI (mpMRI) is currently used for tumor delineation. However, up to 56% of patients will have recurrent disease, defined as International Society of Urological Pathology (ISUP) grade of 2 or greater on follow-up biopsies within 3 y. The objectives of this study were to evaluate recurrence and failure-free survival (FFS) rates in patients treated with HIFU after undergoing prostate-specific membrane antigen (PSMA) PET and to compare delineation and scoring for biopsy-proven lesions between imaging techniques (PSMA PET vs. mpMRI). Methods: This single-center retrospective cohort study included all patients who were scheduled for HIFU between June 2017 and May 2022 and underwent a PSMA PET scan within 6 mo before planned HIFU for initial therapy of low-risk or intermediate-risk PCa (primary HIFU) or local recurrence after radiotherapy (salvage HIFU). Outcomes assessed included FFS, defined as the absence of ISUP grade 2 or greater on follow-up biopsies, progression on imaging, or biochemical recurrence. Tumor detection on mpMRI and PSMA PET was compared using PRIMARY and Prostate Imaging Reporting and Data System (PI-RADS) 2.1 scores for patients with adequate mpMRI and PSMA PET within 6 mo of HIFU. Results: Of the 26 patients included in the cohort, 3 (12%) did not undergo HIFU after the PSMA PET scan because of PCa upstaging. Of the remaining 23 patients, 9 (39%) were treated for recurrent disease and 14 (61%) for primary disease. Over a mean follow-up time of 3.2 y, 15 patients (65%; 95% CI, 42.7%-83.6%) were free of disease at the last follow-up. Eight patients (35%) experienced recurrent or residual disease within 3 y. Image analysis was performed for 18 patients, for a total of 23 lesions, with mean PRIMARY and PI-RADS 2.1 scores of 4.1 (range, 2-5), and 3.3 (range, 2-5), respectively. Lesion detection was rated superior on PET over mpMRI for 12 lesions, whereas mpMRI was superior for 1 lesion. Conclusion: PSMA PET scans performed before HIFU identified 12% of patients who were unsuitable for treatment. The overall improved FFS rate and higher PRIMARY score, when compared with the existing literature, suggest a potential benefit of PSMA PET for tumor delineation.
{"title":"High-Intensity Focused Ultrasound in Prostate Cancer: Can PSMA PET Improve Focal Therapy Outcomes?","authors":"Alexander Maurer,Urs J Muehlematter,Thibika Sivakumar,Ashkan Mortezavi,Jakob Heimer,Basil Kaufmann,Stephan Beintner-Skawran,Michael Messerli,Martin W Huellner,Daniel Eberli,Irene A Burger","doi":"10.2967/jnumed.125.271318","DOIUrl":"https://doi.org/10.2967/jnumed.125.271318","url":null,"abstract":"High-intensity focused ultrasound (HIFU) is an increasingly used, locally ablative therapy option in localized prostate cancer (PCa). Multiparametric MRI (mpMRI) is currently used for tumor delineation. However, up to 56% of patients will have recurrent disease, defined as International Society of Urological Pathology (ISUP) grade of 2 or greater on follow-up biopsies within 3 y. The objectives of this study were to evaluate recurrence and failure-free survival (FFS) rates in patients treated with HIFU after undergoing prostate-specific membrane antigen (PSMA) PET and to compare delineation and scoring for biopsy-proven lesions between imaging techniques (PSMA PET vs. mpMRI). Methods: This single-center retrospective cohort study included all patients who were scheduled for HIFU between June 2017 and May 2022 and underwent a PSMA PET scan within 6 mo before planned HIFU for initial therapy of low-risk or intermediate-risk PCa (primary HIFU) or local recurrence after radiotherapy (salvage HIFU). Outcomes assessed included FFS, defined as the absence of ISUP grade 2 or greater on follow-up biopsies, progression on imaging, or biochemical recurrence. Tumor detection on mpMRI and PSMA PET was compared using PRIMARY and Prostate Imaging Reporting and Data System (PI-RADS) 2.1 scores for patients with adequate mpMRI and PSMA PET within 6 mo of HIFU. Results: Of the 26 patients included in the cohort, 3 (12%) did not undergo HIFU after the PSMA PET scan because of PCa upstaging. Of the remaining 23 patients, 9 (39%) were treated for recurrent disease and 14 (61%) for primary disease. Over a mean follow-up time of 3.2 y, 15 patients (65%; 95% CI, 42.7%-83.6%) were free of disease at the last follow-up. Eight patients (35%) experienced recurrent or residual disease within 3 y. Image analysis was performed for 18 patients, for a total of 23 lesions, with mean PRIMARY and PI-RADS 2.1 scores of 4.1 (range, 2-5), and 3.3 (range, 2-5), respectively. Lesion detection was rated superior on PET over mpMRI for 12 lesions, whereas mpMRI was superior for 1 lesion. Conclusion: PSMA PET scans performed before HIFU identified 12% of patients who were unsuitable for treatment. The overall improved FFS rate and higher PRIMARY score, when compared with the existing literature, suggest a potential benefit of PSMA PET for tumor delineation.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"123 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04DOI: 10.2967/jnumed.125.271646
Mike Teitell,Johannes Czernin
{"title":"Making a Career to Fight Cancer: Johannes Czernin Talks with Mike Teitell About His Career as a Research Physician.","authors":"Mike Teitell,Johannes Czernin","doi":"10.2967/jnumed.125.271646","DOIUrl":"https://doi.org/10.2967/jnumed.125.271646","url":null,"abstract":"","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"130 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-03DOI: 10.2967/jnumed.125.271360
{"title":"Can We Trust Artificial Intelligence in Scientific Publishing?","authors":" ","doi":"10.2967/jnumed.125.271360","DOIUrl":"https://doi.org/10.2967/jnumed.125.271360","url":null,"abstract":"","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"11 1","pages":"1880"},"PeriodicalIF":0.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-03DOI: 10.2967/jnumed.125.271397
Johannes Czernin
{"title":"A New Department for a New Era of Nuclear Medicine and Theranostics.","authors":"Johannes Czernin","doi":"10.2967/jnumed.125.271397","DOIUrl":"https://doi.org/10.2967/jnumed.125.271397","url":null,"abstract":"","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"28 1","pages":"1847"},"PeriodicalIF":0.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-25DOI: 10.2967/jnumed.125.270540
Hossein Jadvar
{"title":"The Final Frontier: Toward Transformative Insights into the Pathophysiologic Adaptations to Microgravity with Molecular Imaging.","authors":"Hossein Jadvar","doi":"10.2967/jnumed.125.270540","DOIUrl":"https://doi.org/10.2967/jnumed.125.270540","url":null,"abstract":"","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-25DOI: 10.2967/jnumed.125.270481
Gokce Belge Bilgin,Brian J Burkett,Cem Bilgin,Jolanta M Durski,Ann T Packard,Patrick J Navin,Matthew P Thorpe,Derek R Johnson,Geoffrey Johnson,Thorvardur R Halfdanarson,Mabel Ryder,Ayse Tuba Kendi
Peptide receptor radionuclide therapy (PRRT) has emerged as a promising treatment for metastatic pheochromocytoma and paraganglioma (mPPGL). This study aimed to evaluate PRRT outcomes in patients with mPPGL in a single institution. Methods: Records of patients with mPPGL who received PRRT were retrospectively reviewed. The outcomes of interest were objective response rate (ORR), disease control rate (DCR), symptomatic benefit, hypertension control, and treatment-related toxicity. ORR included complete response and partial response, whereas DCR encompassed complete response, partial response, and stable disease, determined using RECIST 1.1. Symptomatic benefit was defined as patient-reported symptom improvement relative to baseline. Hypertension control was assessed on the basis of adjustments in antihypertensive medication requirements. Toxicity was evaluated using Common Terminology Criteria for Adverse Events version 5.0. Overall survival and progression-free survival were also evaluated. Results: Of the 15 patients included in our study, 7 (47%) had paraganglioma and 8 (53%) had pheochromocytoma. The mean follow-up duration was 28.4 ± 19.3 mo. PRRT was the initial systemic therapy in 2 patients (13%), and 2 treated with PRRT (13%) underwent retreatment, receiving 8 cycles. Two patients (13%) discontinued PRRT because of disease progression, and the remaining 13 patients (87%) completed all 4 cycles. The ORR was 27%, and the DCR was 73%, including 7 patients with stable disease and 4 with a partial response. The mean PRRT response duration was 16.2 ± 14.2 mo. A reduction in dose or no escalation of antihypertensive therapy was observed in 13 patients (87%). Ten patients (67%) reported symptom improvement. The most common toxicities were grade 1 or 2 anemia and leukopenia (40%). Grade 3 or 4 hematologic toxicities occurred in 2 patients (13%), including 1 with thrombocytopenia (7%) and 1 with myelodysplastic syndrome (7%). No moderate or severe nephrotoxicity was observed. Hypertensive crises occurred in 2 patients (13%), 1 with a prior history of such events. The median overall survival was 54.8 mo (95% CI, 6.8-102.8 mo), and the median progression-free survival was 26.9 mo (95% CI, 13.3-40.5 mo). Conclusion: Our findings suggest that PRRT remains a therapeutic strategy for mPPGL, is well-tolerated, and may improve cancer-related symptoms. Large-scale prospective studies are needed to validate structural responses and durability.
{"title":"Outcomes of Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in Patients with Metastatic Pheochromocytoma and Paraganglioma.","authors":"Gokce Belge Bilgin,Brian J Burkett,Cem Bilgin,Jolanta M Durski,Ann T Packard,Patrick J Navin,Matthew P Thorpe,Derek R Johnson,Geoffrey Johnson,Thorvardur R Halfdanarson,Mabel Ryder,Ayse Tuba Kendi","doi":"10.2967/jnumed.125.270481","DOIUrl":"https://doi.org/10.2967/jnumed.125.270481","url":null,"abstract":"Peptide receptor radionuclide therapy (PRRT) has emerged as a promising treatment for metastatic pheochromocytoma and paraganglioma (mPPGL). This study aimed to evaluate PRRT outcomes in patients with mPPGL in a single institution. Methods: Records of patients with mPPGL who received PRRT were retrospectively reviewed. The outcomes of interest were objective response rate (ORR), disease control rate (DCR), symptomatic benefit, hypertension control, and treatment-related toxicity. ORR included complete response and partial response, whereas DCR encompassed complete response, partial response, and stable disease, determined using RECIST 1.1. Symptomatic benefit was defined as patient-reported symptom improvement relative to baseline. Hypertension control was assessed on the basis of adjustments in antihypertensive medication requirements. Toxicity was evaluated using Common Terminology Criteria for Adverse Events version 5.0. Overall survival and progression-free survival were also evaluated. Results: Of the 15 patients included in our study, 7 (47%) had paraganglioma and 8 (53%) had pheochromocytoma. The mean follow-up duration was 28.4 ± 19.3 mo. PRRT was the initial systemic therapy in 2 patients (13%), and 2 treated with PRRT (13%) underwent retreatment, receiving 8 cycles. Two patients (13%) discontinued PRRT because of disease progression, and the remaining 13 patients (87%) completed all 4 cycles. The ORR was 27%, and the DCR was 73%, including 7 patients with stable disease and 4 with a partial response. The mean PRRT response duration was 16.2 ± 14.2 mo. A reduction in dose or no escalation of antihypertensive therapy was observed in 13 patients (87%). Ten patients (67%) reported symptom improvement. The most common toxicities were grade 1 or 2 anemia and leukopenia (40%). Grade 3 or 4 hematologic toxicities occurred in 2 patients (13%), including 1 with thrombocytopenia (7%) and 1 with myelodysplastic syndrome (7%). No moderate or severe nephrotoxicity was observed. Hypertensive crises occurred in 2 patients (13%), 1 with a prior history of such events. The median overall survival was 54.8 mo (95% CI, 6.8-102.8 mo), and the median progression-free survival was 26.9 mo (95% CI, 13.3-40.5 mo). Conclusion: Our findings suggest that PRRT remains a therapeutic strategy for mPPGL, is well-tolerated, and may improve cancer-related symptoms. Large-scale prospective studies are needed to validate structural responses and durability.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"205 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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