Pub Date : 2024-10-01DOI: 10.2967/jnumed.124.268169
Johanna S Enke, Kathrin Ritzel, Evelyn Asbach, Nic G Reitsam, Bruno Märkl, Thomas Knösel, Denise Brüdgam, Malte Kircher, Christian H Pfob, Ralph A Bundschuh, Andreas Rinscheid, Bernd Nittbaur, Georgine Wienand, Margret Schottelius, Martin Reincke, Constantin Lapa, Alexander Dierks
C-X-C motif chemokine receptor 4 (CXCR4)-directed imaging has gained clinical interest in aiding clinical diagnostics in primary aldosteronism (PA). We retrospectively evaluated the feasibility of CXCR4-directed scintigraphy using the novel CXCR-4 ligand [99mTc]Tc-pentixatec in patients with PA. Methods: Six patients (mean age ± SD, 49 ± 15 y) underwent CXCR4-directed scintigraphy (including planar imaging and SPECT/CT) 30, 120, and 240 min after injection of 435 ± 50 MBq of [99mTc]Tc-pentixatec. Adrenal CXCR4 expression was analyzed by calculating lesion-to-contralateral ratios (LCRs). Imaging results were correlated to clinical information. Histopathology and clinical follow-up served as the standard of reference. Results: Three subjects showed lateralization of adrenal tracer accumulation, with a mean maximum lesion-to-contralateral ratio of 1.65 (range, 1.52-1.70), which correlated with morphologic findings on CT. One individual underwent adrenalectomy and presented with complete biochemical and clinical remission at follow-up. Histopathologic workup confirmed unilateral aldosterone-producing adenoma. Conclusion: [99mTc]Tc-pentixatec scintigraphy with SPECT in patients with PA is feasible and might offer a valuable alternative to CXCR4-directed imaging with [68Ga]Ga-pentixafor PET.
{"title":"C-X-C Motif Chemokine Receptor 4-Directed Scintigraphy Using [<sup>99m</sup>Tc]Tc-Pentixatec in Primary Aldosteronism: A Proof-of-Concept Study.","authors":"Johanna S Enke, Kathrin Ritzel, Evelyn Asbach, Nic G Reitsam, Bruno Märkl, Thomas Knösel, Denise Brüdgam, Malte Kircher, Christian H Pfob, Ralph A Bundschuh, Andreas Rinscheid, Bernd Nittbaur, Georgine Wienand, Margret Schottelius, Martin Reincke, Constantin Lapa, Alexander Dierks","doi":"10.2967/jnumed.124.268169","DOIUrl":"10.2967/jnumed.124.268169","url":null,"abstract":"<p><p>C-X-C motif chemokine receptor 4 (CXCR4)-directed imaging has gained clinical interest in aiding clinical diagnostics in primary aldosteronism (PA). We retrospectively evaluated the feasibility of CXCR4-directed scintigraphy using the novel CXCR-4 ligand [<sup>99m</sup>Tc]Tc-pentixatec in patients with PA. <b>Methods:</b> Six patients (mean age ± SD, 49 ± 15 y) underwent CXCR4-directed scintigraphy (including planar imaging and SPECT/CT) 30, 120, and 240 min after injection of 435 ± 50 MBq of [<sup>99m</sup>Tc]Tc-pentixatec. Adrenal CXCR4 expression was analyzed by calculating lesion-to-contralateral ratios (LCRs). Imaging results were correlated to clinical information. Histopathology and clinical follow-up served as the standard of reference. <b>Results:</b> Three subjects showed lateralization of adrenal tracer accumulation, with a mean maximum lesion-to-contralateral ratio of 1.65 (range, 1.52-1.70), which correlated with morphologic findings on CT. One individual underwent adrenalectomy and presented with complete biochemical and clinical remission at follow-up. Histopathologic workup confirmed unilateral aldosterone-producing adenoma. <b>Conclusion:</b> [<sup>99m</sup>Tc]Tc-pentixatec scintigraphy with SPECT in patients with PA is feasible and might offer a valuable alternative to CXCR4-directed imaging with [<sup>68</sup>Ga]Ga-pentixafor PET.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1640-1644"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142203","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 : 2024-10-01DOI: 10.2967/jnumed.124.268341
Irène Buvat, Wolfgang A Weber
{"title":"Is ChatGPT a Reliable Ghostwriter?","authors":"Irène Buvat, Wolfgang A Weber","doi":"10.2967/jnumed.124.268341","DOIUrl":"10.2967/jnumed.124.268341","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1499-1502"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019928","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 : 2024-10-01DOI: 10.2967/jnumed.124.267751
Matteo Bauckneht, Francesca D'Amico, Domenico Albano, Michele Balma, Camilla Cabrini, Francesco Dondi, Tania Di Raimondo, Virginia Liberini, Luca Sofia, Simona Peano, Mattia Riondato, Giuseppe Fornarini, Riccardo Laudicella, Luca Carmisciano, Egesta Lopci, Roberta Zanca, Marcello Rodari, Stefano Raffa, Maria Isabella Donegani, Daniela Dubois, Leonardo Peñuela, Cecilia Marini, Francesco Bertagna, Alberto Papaleo, Silvia Morbelli, Gianmario Sambuceti, Marta Ponzano, Alessio Signori
Unspecific bone uptake (UBU) related to [18F]PSMA-1007 PET/CT imaging represents a clinical challenge. We aimed to assess whether a combination of clinical, biochemical, and imaging parameters could predict skeletal metastases in patients with [18F]PSMA-1007 bone focal uptake, aiding in result interpretation. Methods: We retrospectively analyzed [18F]PSMA-1007 PET/CT performed in hormone-sensitive prostate cancer (PCa) patients at 3 tertiary-level cancer centers. A fourth center was involved in performing an external validation. For each, a volume of interest was drawn using a threshold method to extract SUVmax, SUVmean, PSMA tumor volume, and total lesion PSMA. The same volume of interest was applied to CT images to calculate the mean Hounsfield units (HUmean) and maximum Hounsfield units. Clinical and laboratory data were collected from electronic medical records. A composite reference standard, including follow-up histopathology, biochemistry, and imaging data, was used to distinguish between PCa bone metastases and UBU. PET readers with less (n = 2) or more (n = 2) experience, masked to the reference standard, were asked to visually rate a subset of focal bone uptake (n = 178) as PCa metastases or not. Results: In total, 448 bone [18F]PSMA-1007 focal uptake specimens were identified in 267 PCa patients. Of the 448 uptake samples, 188 (41.9%) corresponded to PCa metastases. Ongoing androgen deprivation therapy at PET/CT (P < 0.001) with determination of SUVmax (P < 0.001) and HUmean (P < 0.001) independently predicted bone metastases. A composite prediction score, the bone uptake metastatic probability (BUMP) score, achieving an area under the receiver-operating-characteristic curve (AUC) of 0.87, was validated through a 10-fold internal and external validation (n = 89 bone uptake, 51% metastatic; AUC, 0.92). The BUMP score's AUC was significantly higher than that of HUmean (AUC, 0.62) and remained high among lesions with HUmean in the first tertile (AUC, 0.80). A decision-curve analysis showed a higher net benefit with the score. Compared with the visual assessment, the BUMP score provided added value in terms of specificity in less-experienced PET readers (88% vs. 54%, P < 0.001). Conclusion: The BUMP score accurately distinguished UBU from bone metastases in PCa patients with [18F]PSMA-1007 focal bone uptake at PET imaging, offering additional value compared with the simple assessment of the osteoblastic CT correlate. Its use could help clinicians interpret imaging results, particularly those with less experience, potentially reducing the risk of patient overstaging.
{"title":"Composite Prediction Score to Interpret Bone Focal Uptake in Hormone-Sensitive Prostate Cancer Patients Imaged with [<sup>18</sup>F]PSMA-1007 PET/CT.","authors":"Matteo Bauckneht, Francesca D'Amico, Domenico Albano, Michele Balma, Camilla Cabrini, Francesco Dondi, Tania Di Raimondo, Virginia Liberini, Luca Sofia, Simona Peano, Mattia Riondato, Giuseppe Fornarini, Riccardo Laudicella, Luca Carmisciano, Egesta Lopci, Roberta Zanca, Marcello Rodari, Stefano Raffa, Maria Isabella Donegani, Daniela Dubois, Leonardo Peñuela, Cecilia Marini, Francesco Bertagna, Alberto Papaleo, Silvia Morbelli, Gianmario Sambuceti, Marta Ponzano, Alessio Signori","doi":"10.2967/jnumed.124.267751","DOIUrl":"10.2967/jnumed.124.267751","url":null,"abstract":"<p><p>Unspecific bone uptake (UBU) related to [<sup>18</sup>F]PSMA-1007 PET/CT imaging represents a clinical challenge. We aimed to assess whether a combination of clinical, biochemical, and imaging parameters could predict skeletal metastases in patients with [<sup>18</sup>F]PSMA-1007 bone focal uptake, aiding in result interpretation. <b>Methods:</b> We retrospectively analyzed [<sup>18</sup>F]PSMA-1007 PET/CT performed in hormone-sensitive prostate cancer (PCa) patients at 3 tertiary-level cancer centers. A fourth center was involved in performing an external validation. For each, a volume of interest was drawn using a threshold method to extract SUV<sub>max</sub>, SUV<sub>mean</sub>, PSMA tumor volume, and total lesion PSMA. The same volume of interest was applied to CT images to calculate the mean Hounsfield units (HU<sub>mean</sub>) and maximum Hounsfield units. Clinical and laboratory data were collected from electronic medical records. A composite reference standard, including follow-up histopathology, biochemistry, and imaging data, was used to distinguish between PCa bone metastases and UBU. PET readers with less (<i>n</i> = 2) or more (<i>n</i> = 2) experience, masked to the reference standard, were asked to visually rate a subset of focal bone uptake (<i>n</i> = 178) as PCa metastases or not. <b>Results:</b> In total, 448 bone [<sup>18</sup>F]PSMA-1007 focal uptake specimens were identified in 267 PCa patients. Of the 448 uptake samples, 188 (41.9%) corresponded to PCa metastases. Ongoing androgen deprivation therapy at PET/CT (<i>P</i> < 0.001) with determination of SUV<sub>max</sub> (<i>P</i> < 0.001) and HU<sub>mean</sub> (<i>P</i> < 0.001) independently predicted bone metastases. A composite prediction score, the bone uptake metastatic probability (BUMP) score, achieving an area under the receiver-operating-characteristic curve (AUC) of 0.87, was validated through a 10-fold internal and external validation (<i>n</i> = 89 bone uptake, 51% metastatic; AUC, 0.92). The BUMP score's AUC was significantly higher than that of HU<sub>mean</sub> (AUC, 0.62) and remained high among lesions with HU<sub>mean</sub> in the first tertile (AUC, 0.80). A decision-curve analysis showed a higher net benefit with the score. Compared with the visual assessment, the BUMP score provided added value in terms of specificity in less-experienced PET readers (88% vs. 54%, <i>P</i> < 0.001). <b>Conclusion:</b> The BUMP score accurately distinguished UBU from bone metastases in PCa patients with [<sup>18</sup>F]PSMA-1007 focal bone uptake at PET imaging, offering additional value compared with the simple assessment of the osteoblastic CT correlate. Its use could help clinicians interpret imaging results, particularly those with less experience, potentially reducing the risk of patient overstaging.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1577-1583"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.2967/jnumed.124.267591
Pan Thin, Masatoshi Hotta, Andrei Gafita, Tristan Grogan, Johannes Czernin, Jeremie Calais, Ida Sonni
This analysis aimed to identify clinical factors associated with positivity on repeat 68Ga-PSMA-11 PET/CT after a negative scan in patients with recurrent prostate cancer (PCa) under observation. Methods: This single-center, retrospective analysis included patients who underwent at least 2 68Ga-PSMA-11 PET/CT scans (PET1 and PET2) at UCLA between October 2016 and June 2021 for recurrent PCa with negative PET1 and no PCa-related treatments between the 2 scans. Using Prostate Cancer Molecular Imaging Standardized Evaluation criteria to define negative and positive scans, the final cohort was divided into PET2-negative (PET2-Neg) and PET2-positive (PET2-Pos). The same PET1 was used twice in the more than 2 PET cases with inclusion criteria fulfilled. Patient characteristics and clinical parameters were compared between the 2 cohorts using Mann-Whitney U test and Fisher exact test. Areas under the curve (AUCs) of the receiver operating characteristic and the Youden index were computed to determine the discrimination ability of statistically significant factors and specific cut points that maximized sensitivity and specificity, respectively. Results: The final analysis included 83 sets of 2 PET/CT scans from 70 patients. Thirty-nine of 83 (47%) sets were PET2-Neg, and 44 of 83 (53%) sets were PET2-Pos. Prostate-specific antigen (PSA) increased from PET1 to PET2 for all 83 (100%) sets of scans. Median PSA at PET1 was 0.4 ng/mL (interquartile range, 0.2-1.0) and at PET2 was 1.6 ng/mL (interquartile range, 0.9-3.8). We found higher serum PSA at PET2 (median, 1.8 vs. 1.1 ng/mL; P = 0.015), absolute PSA difference (median, 1.4 vs. 0.7 ng/mL; P = 0.006), percentage of PSA change (median, +270.4% vs. +150.0%: P = 0.031), and median PSA velocity (0.044 vs. 0.017 ng/mL/wk, P = 0.002) and shorter PSA doubling time (DT; median, 5.1 vs. 8.3 mo; P = 0.006) in the PET2-Pos cohort than in the PET2-Neg cohort. Receiver operating characteristic curves showed cutoffs for PSA at PET2 of 4.80 ng/mL (sensitivity, 34%; specificity, 92%; AUC, 0.66), absolute PSA difference of 0.95 ng/mL (sensitivity, 62%; specificity, 71%; AUC, 0.68), percentage of PSA change of a positive 289.50% (sensitivity, 48%; specificity, 82%; AUC, 0.64), PSA velocity of 0.033 ng/mL/wk (sensitivity, 57%; specificity, 80%; AUC, 0.70), and PSA DT of 7.91 mo (sensitivity, 71%; specificity, 62%; AUC, 0.67). Conclusion: Patients with recurrent PCa under observation after a negative 68Ga-PSMA-11 PET/CT scan with markedly elevated serum PSA levels and shorter PSA DT are more likely to have positive findings on repeat 68Ga-PSMA-11 PET/CT.
{"title":"Clinical Factors That Influence Repeat <sup>68</sup>Ga-PSMA-11 PET/CT Scan Positivity in Patients with Recurrent Prostate Cancer Under Observation After a Negative <sup>68</sup>Ga-PSMA-11 PET/CT Scan: A Single-Center Retrospective Study.","authors":"Pan Thin, Masatoshi Hotta, Andrei Gafita, Tristan Grogan, Johannes Czernin, Jeremie Calais, Ida Sonni","doi":"10.2967/jnumed.124.267591","DOIUrl":"10.2967/jnumed.124.267591","url":null,"abstract":"<p><p>This analysis aimed to identify clinical factors associated with positivity on repeat <sup>68</sup>Ga-PSMA-11 PET/CT after a negative scan in patients with recurrent prostate cancer (PCa) under observation. <b>Methods:</b> This single-center, retrospective analysis included patients who underwent at least 2 <sup>68</sup>Ga-PSMA-11 PET/CT scans (PET1 and PET2) at UCLA between October 2016 and June 2021 for recurrent PCa with negative PET1 and no PCa-related treatments between the 2 scans. Using Prostate Cancer Molecular Imaging Standardized Evaluation criteria to define negative and positive scans, the final cohort was divided into PET2-negative (PET2-Neg) and PET2-positive (PET2-Pos). The same PET1 was used twice in the more than 2 PET cases with inclusion criteria fulfilled. Patient characteristics and clinical parameters were compared between the 2 cohorts using Mann-Whitney <i>U</i> test and Fisher exact test. Areas under the curve (AUCs) of the receiver operating characteristic and the Youden index were computed to determine the discrimination ability of statistically significant factors and specific cut points that maximized sensitivity and specificity, respectively. <b>Results:</b> The final analysis included 83 sets of 2 PET/CT scans from 70 patients. Thirty-nine of 83 (47%) sets were PET2-Neg, and 44 of 83 (53%) sets were PET2-Pos. Prostate-specific antigen (PSA) increased from PET1 to PET2 for all 83 (100%) sets of scans. Median PSA at PET1 was 0.4 ng/mL (interquartile range, 0.2-1.0) and at PET2 was 1.6 ng/mL (interquartile range, 0.9-3.8). We found higher serum PSA at PET2 (median, 1.8 vs. 1.1 ng/mL; <i>P</i> = 0.015), absolute PSA difference (median, 1.4 vs. 0.7 ng/mL; <i>P</i> = 0.006), percentage of PSA change (median, +270.4% vs. +150.0%: <i>P</i> = 0.031), and median PSA velocity (0.044 vs. 0.017 ng/mL/wk, <i>P</i> = 0.002) and shorter PSA doubling time (DT; median, 5.1 vs. 8.3 mo; <i>P</i> = 0.006) in the PET2-Pos cohort than in the PET2-Neg cohort. Receiver operating characteristic curves showed cutoffs for PSA at PET2 of 4.80 ng/mL (sensitivity, 34%; specificity, 92%; AUC, 0.66), absolute PSA difference of 0.95 ng/mL (sensitivity, 62%; specificity, 71%; AUC, 0.68), percentage of PSA change of a positive 289.50% (sensitivity, 48%; specificity, 82%; AUC, 0.64), PSA velocity of 0.033 ng/mL/wk (sensitivity, 57%; specificity, 80%; AUC, 0.70), and PSA DT of 7.91 mo (sensitivity, 71%; specificity, 62%; AUC, 0.67). <b>Conclusion:</b> Patients with recurrent PCa under observation after a negative <sup>68</sup>Ga-PSMA-11 PET/CT scan with markedly elevated serum PSA levels and shorter PSA DT are more likely to have positive findings on repeat <sup>68</sup>Ga-PSMA-11 PET/CT.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1571-1576"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019927","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 : 2024-10-01DOI: 10.2967/jnumed.124.267518
Fabio Monastero, Luigia Vetrone, Lina Cardisciani, Matteo Renzulli, Enrico Prosperi, Matteo Cescon, Matteo Ravaioli, Stefano Fanti, Andrea Farolfi, Francesco Vasuri
{"title":"[<sup>68</sup>Ga]Ga-PSMA-11 PET/CT-Positive Hepatic Inflammatory Pseudotumor: Possible PSMA-Avid Pitfall in Nuclear Imaging.","authors":"Fabio Monastero, Luigia Vetrone, Lina Cardisciani, Matteo Renzulli, Enrico Prosperi, Matteo Cescon, Matteo Ravaioli, Stefano Fanti, Andrea Farolfi, Francesco Vasuri","doi":"10.2967/jnumed.124.267518","DOIUrl":"10.2967/jnumed.124.267518","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1658-1659"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319386","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 : 2024-10-01DOI: 10.2967/jnumed.124.267924
Aaron Jun Ning Wong, Hyun Soo Ko, Michael S Hofman
{"title":"Navigating the Future of Prostate Cancer Care: AI-Driven Imaging and Theranostics Through the Lens of RELAINCE.","authors":"Aaron Jun Ning Wong, Hyun Soo Ko, Michael S Hofman","doi":"10.2967/jnumed.124.267924","DOIUrl":"10.2967/jnumed.124.267924","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1503-1504"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116601","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 : 2024-10-01DOI: 10.2967/jnumed.123.267274
Tharani Sivakumaran, Anthony Cardin, Jason Callahan, Hui-Li Wong, Richard W Tothill, Rodney J Hicks, Linda R Mileshkin
Cancer of unknown primary (CUP) represents a heterogeneous group of metastatic tumors for which standardized diagnostic work-up fails to identify the primary site. We aimed to describe the Peter MacCallum Cancer Centre experience with 18F-FDG PET/CT in extracervical CUP with respect to detection of a primary site and its impact on management. A secondary aim was to compare overall survival (OS) in patients with and without a detected primary site. Methods: CUP patients treated between 2014 and 2020 were identified from medical oncology clinics and 18F-FDG PET/CT records. Information collated from electronic medical records included the suspected primary site and treatment details before and after 18F-FDG PET/CT. Clinicopathologic details and genomic analysis were used to determine the clinically suspected primary site and compared against 2 independent masked reads of 18F-FDG PET/CT images by nuclear medicine specialists to determine sensitivity, specificity, accuracy, and the rate of detection of the primary site. Results: We identified 147 patients, 65% of whom had undergone molecular profiling. The median age at diagnosis was 61 y (range, 20-84 y), and the median follow-up time was 74 mo (range, 26-83 mo). Eighty-two percent were classified as having an unfavorable CUP subtype as per international guidelines.18F-FDG PET/CT demonstrated a primary site detection rate of 41%, resulted in a change in management in 22%, and identified previously occult disease sites in 37%. Median OS was 16.8 mo for all patients and 104.7 and 12.1 mo for favorable and unfavorable CUP subtypes, respectively (P < 0.0001). Median OS in CUP patients when using 18F-FDG PET/CT, clinicopathologic, and genomic information was 19.8 and 8.5 mo when a primary site was detected and not detected, respectively (P = 0.016). Multivariable analysis of survival adjusted for age and sex remained significant for identification of a potential primary site (P < 0.001), a favorable CUP (P < 0.001), and an Eastern Cooperative Oncology Group status of 1 or less (P < 0.001). Conclusion:18F-FDG PET/CT plays a complementary role in CUP diagnostic work-up and was able to determine the likely primary site in 41% of cases. OS is improved with primary site identification, demonstrating the value of access to diagnostic 18F-FDG PET/CT for CUP patients.
{"title":"Evaluating the Utility of <sup>18</sup>F-FDG PET/CT in Cancer of Unknown Primary.","authors":"Tharani Sivakumaran, Anthony Cardin, Jason Callahan, Hui-Li Wong, Richard W Tothill, Rodney J Hicks, Linda R Mileshkin","doi":"10.2967/jnumed.123.267274","DOIUrl":"10.2967/jnumed.123.267274","url":null,"abstract":"<p><p>Cancer of unknown primary (CUP) represents a heterogeneous group of metastatic tumors for which standardized diagnostic work-up fails to identify the primary site. We aimed to describe the Peter MacCallum Cancer Centre experience with <sup>18</sup>F-FDG PET/CT in extracervical CUP with respect to detection of a primary site and its impact on management. A secondary aim was to compare overall survival (OS) in patients with and without a detected primary site. <b>Methods:</b> CUP patients treated between 2014 and 2020 were identified from medical oncology clinics and <sup>18</sup>F-FDG PET/CT records. Information collated from electronic medical records included the suspected primary site and treatment details before and after <sup>18</sup>F-FDG PET/CT. Clinicopathologic details and genomic analysis were used to determine the clinically suspected primary site and compared against 2 independent masked reads of <sup>18</sup>F-FDG PET/CT images by nuclear medicine specialists to determine sensitivity, specificity, accuracy, and the rate of detection of the primary site. <b>Results:</b> We identified 147 patients, 65% of whom had undergone molecular profiling. The median age at diagnosis was 61 y (range, 20-84 y), and the median follow-up time was 74 mo (range, 26-83 mo). Eighty-two percent were classified as having an unfavorable CUP subtype as per international guidelines.<sup>18</sup>F-FDG PET/CT demonstrated a primary site detection rate of 41%, resulted in a change in management in 22%, and identified previously occult disease sites in 37%. Median OS was 16.8 mo for all patients and 104.7 and 12.1 mo for favorable and unfavorable CUP subtypes, respectively (<i>P</i> < 0.0001). Median OS in CUP patients when using <sup>18</sup>F-FDG PET/CT, clinicopathologic, and genomic information was 19.8 and 8.5 mo when a primary site was detected and not detected, respectively (<i>P</i> = 0.016). Multivariable analysis of survival adjusted for age and sex remained significant for identification of a potential primary site (<i>P</i> < 0.001), a favorable CUP (<i>P</i> < 0.001), and an Eastern Cooperative Oncology Group status of 1 or less (<i>P</i> < 0.001). <b>Conclusion:</b> <sup>18</sup>F-FDG PET/CT plays a complementary role in CUP diagnostic work-up and was able to determine the likely primary site in 41% of cases. OS is improved with primary site identification, demonstrating the value of access to diagnostic <sup>18</sup>F-FDG PET/CT for CUP patients.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1557-1563"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142204","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 : 2024-10-01DOI: 10.2967/jnumed.124.267685
Brett A Vaughn, Sang-Gyu Lee, Daniela Burnes Vargas, Shin Seo, Sara S Rinne, Hong Xu, Hong-Fen Guo, Alexandre B Le Roux, Leah Gajecki, Simone Krebs, Guangbin Yang, Ouathek Ouerfelli, Pat B Zanzonico, Edward K Fung, Samantha St Jean, Sebastian E Carrasco, Achim Jungbluth, Nai Kong V Cheung, Steven M Larson, Darren R Veach, Sarah M Cheal
<p><p>Radiolabeled small-molecule DOTA-haptens can be combined with antitumor/anti-DOTA bispecific antibodies (BsAbs) for pretargeted radioimmunotherapy (PRIT). For optimized delivery of the theranostic γ- and β-emitting isotope <sup>177</sup>Lu with DOTA-based PRIT (DOTA-PRIT), bivalent Gemini (DOTA-Bn-thiourea-PEG4-thiourea-Bn-DOTA, aka (3,6,9,12-tetraoxatetradecane-1,14-diyl)bis(DOTA-benzyl thiourea)) was developed. <b>Methods:</b> Gemini was synthesized by linking 2 <i>S</i>-2-(4-isothiocyanatobenzyl)-DOTA molecules together via a 1,14-diamino-PEG4 linker. [<sup>177</sup>Lu]Lu-Gemini was prepared with no-carrier-added <sup>177</sup>LuCl<sub>3</sub> to a molar-specific activity of 123 GBq/μmol and radiochemical purity of more than 99%. The specificity of BsAb-<sup>177</sup>Lu-Gemini was verified in vitro. Subsequently, we evaluated biodistribution and whole-body clearance for [<sup>177</sup>Lu]Lu-Gemini and, for comparison, our gold-standard monovalent [<sup>177</sup>Lu]Lu-<i>S</i>-2-(4-aminobenzyl)-DOTA ([<sup>177</sup>Lu]Lu-DOTA-Bn) in naïve (tumor-free) athymic nude mice. For our proof-of-concept system, a 3-step pretargeting approach was performed with an established DOTA-PRIT regimen (anti-GPA33/anti-DOTA IgG-scFv BsAb, a clearing agent, and [<sup>177</sup>Lu]Lu-Gemini) in mouse models. <b>Results:</b> Initial in vivo studies showed that [<sup>177</sup>Lu]Lu-Gemini behaved similarly to [<sup>177</sup>Lu]Lu-DOTA-Bn, with almost identical blood and whole-body clearance kinetics, as well as biodistribution and mouse kidney dosimetry. Pretargeting [<sup>177</sup>Lu]Lu-Gemini to GPA33-expressing SW1222 human colorectal xenografts was highly effective, leading to absorbed doses of [<sup>177</sup>Lu]Lu-Gemini for blood, tumor, liver, spleen, and kidneys of 3.99, 455, 6.93, 5.36, and 14.0 cGy/MBq, respectively. Tumor-to-normal tissue absorbed-dose ratios (i.e., therapeutic indices [TIs]) for the blood and kidneys were 114 and 33, respectively. In addition, we demonstrate that the use of bivalent [<sup>177</sup>Lu]Lu-Gemini in DOTA-PRIT leads to improved TIs and augmented [<sup>177</sup>Lu]Lu-Gemini tumor uptake and retention in comparison to monovalent [<sup>177</sup>Lu]Lu-DOTA-Bn. Finally, we established efficacy in SW1222 tumor-bearing mice, demonstrating that a single injection of anti-GPA33 DOTA-PRIT with 44 MBq (1.2 mCi) of [<sup>177</sup>Lu]Lu-Gemini (estimated tumor-absorbed dose, 200 Gy) induced complete responses in 5 of 5 animals and a histologic cure in 2 of 5 (40%) animals. Moreover, a significant increase in survival compared with nontreated controls was noted (maximum tolerated dose not reached). <b>Conclusion:</b> We have developed a bivalent DOTA-radiohapten, [<sup>177</sup>Lu]Lu-Gemini, that showed improved radiopharmacology for DOTA-PRIT application. The use of bivalent [<sup>177</sup>Lu]Lu-Gemini in DOTA-PRIT, as opposed to monovalent [<sup>177</sup>Lu]Lu-DOTA-Bn, allows curative treatments with considerably less administered <
{"title":"Theranostic GPA33-Pretargeted Radioimmunotherapy of Human Colorectal Carcinoma with a Bivalent <sup>177</sup>Lu-Labeled Radiohapten.","authors":"Brett A Vaughn, Sang-Gyu Lee, Daniela Burnes Vargas, Shin Seo, Sara S Rinne, Hong Xu, Hong-Fen Guo, Alexandre B Le Roux, Leah Gajecki, Simone Krebs, Guangbin Yang, Ouathek Ouerfelli, Pat B Zanzonico, Edward K Fung, Samantha St Jean, Sebastian E Carrasco, Achim Jungbluth, Nai Kong V Cheung, Steven M Larson, Darren R Veach, Sarah M Cheal","doi":"10.2967/jnumed.124.267685","DOIUrl":"10.2967/jnumed.124.267685","url":null,"abstract":"<p><p>Radiolabeled small-molecule DOTA-haptens can be combined with antitumor/anti-DOTA bispecific antibodies (BsAbs) for pretargeted radioimmunotherapy (PRIT). For optimized delivery of the theranostic γ- and β-emitting isotope <sup>177</sup>Lu with DOTA-based PRIT (DOTA-PRIT), bivalent Gemini (DOTA-Bn-thiourea-PEG4-thiourea-Bn-DOTA, aka (3,6,9,12-tetraoxatetradecane-1,14-diyl)bis(DOTA-benzyl thiourea)) was developed. <b>Methods:</b> Gemini was synthesized by linking 2 <i>S</i>-2-(4-isothiocyanatobenzyl)-DOTA molecules together via a 1,14-diamino-PEG4 linker. [<sup>177</sup>Lu]Lu-Gemini was prepared with no-carrier-added <sup>177</sup>LuCl<sub>3</sub> to a molar-specific activity of 123 GBq/μmol and radiochemical purity of more than 99%. The specificity of BsAb-<sup>177</sup>Lu-Gemini was verified in vitro. Subsequently, we evaluated biodistribution and whole-body clearance for [<sup>177</sup>Lu]Lu-Gemini and, for comparison, our gold-standard monovalent [<sup>177</sup>Lu]Lu-<i>S</i>-2-(4-aminobenzyl)-DOTA ([<sup>177</sup>Lu]Lu-DOTA-Bn) in naïve (tumor-free) athymic nude mice. For our proof-of-concept system, a 3-step pretargeting approach was performed with an established DOTA-PRIT regimen (anti-GPA33/anti-DOTA IgG-scFv BsAb, a clearing agent, and [<sup>177</sup>Lu]Lu-Gemini) in mouse models. <b>Results:</b> Initial in vivo studies showed that [<sup>177</sup>Lu]Lu-Gemini behaved similarly to [<sup>177</sup>Lu]Lu-DOTA-Bn, with almost identical blood and whole-body clearance kinetics, as well as biodistribution and mouse kidney dosimetry. Pretargeting [<sup>177</sup>Lu]Lu-Gemini to GPA33-expressing SW1222 human colorectal xenografts was highly effective, leading to absorbed doses of [<sup>177</sup>Lu]Lu-Gemini for blood, tumor, liver, spleen, and kidneys of 3.99, 455, 6.93, 5.36, and 14.0 cGy/MBq, respectively. Tumor-to-normal tissue absorbed-dose ratios (i.e., therapeutic indices [TIs]) for the blood and kidneys were 114 and 33, respectively. In addition, we demonstrate that the use of bivalent [<sup>177</sup>Lu]Lu-Gemini in DOTA-PRIT leads to improved TIs and augmented [<sup>177</sup>Lu]Lu-Gemini tumor uptake and retention in comparison to monovalent [<sup>177</sup>Lu]Lu-DOTA-Bn. Finally, we established efficacy in SW1222 tumor-bearing mice, demonstrating that a single injection of anti-GPA33 DOTA-PRIT with 44 MBq (1.2 mCi) of [<sup>177</sup>Lu]Lu-Gemini (estimated tumor-absorbed dose, 200 Gy) induced complete responses in 5 of 5 animals and a histologic cure in 2 of 5 (40%) animals. Moreover, a significant increase in survival compared with nontreated controls was noted (maximum tolerated dose not reached). <b>Conclusion:</b> We have developed a bivalent DOTA-radiohapten, [<sup>177</sup>Lu]Lu-Gemini, that showed improved radiopharmacology for DOTA-PRIT application. The use of bivalent [<sup>177</sup>Lu]Lu-Gemini in DOTA-PRIT, as opposed to monovalent [<sup>177</sup>Lu]Lu-DOTA-Bn, allows curative treatments with considerably less administered <","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1611-1618"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.2967/jnumed.124.267783
Fijs W B van Leeuwen, Tessa Buckle, Matthias N van Oosterom, Daphne D D Rietbergen
Following early acceptance by urologists, the use of surgical robotic platforms is rapidly spreading to other surgical fields. This empowerment of surgical perception via robotic advances occurs in parallel to developments in intraoperative molecular imaging. Convergence of these efforts creates a logical incentive to advance the decades-old image-guided robotics paradigm. This yields new radioguided surgery strategies set to optimally exploit the symbiosis between the growing clinical translation of robotics and molecular imaging. These strategies intend to advance surgical precision by increasing dexterity and optimizing surgical decision-making. In this state-of-the-art review, topic-related developments in chemistry (tracer development) and engineering (medical device development) are discussed, and future scientific robotic growth markets for molecular imaging are presented.
{"title":"The Rise of Molecular Image-Guided Robotic Surgery.","authors":"Fijs W B van Leeuwen, Tessa Buckle, Matthias N van Oosterom, Daphne D D Rietbergen","doi":"10.2967/jnumed.124.267783","DOIUrl":"10.2967/jnumed.124.267783","url":null,"abstract":"<p><p>Following early acceptance by urologists, the use of surgical robotic platforms is rapidly spreading to other surgical fields. This empowerment of surgical perception via robotic advances occurs in parallel to developments in intraoperative molecular imaging. Convergence of these efforts creates a logical incentive to advance the decades-old image-guided robotics paradigm. This yields new radioguided surgery strategies set to optimally exploit the symbiosis between the growing clinical translation of robotics and molecular imaging. These strategies intend to advance surgical precision by increasing dexterity and optimizing surgical decision-making. In this state-of-the-art review, topic-related developments in chemistry (tracer development) and engineering (medical device development) are discussed, and future scientific robotic growth markets for molecular imaging are presented.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1505-1511"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592496","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 : 2024-09-19DOI: 10.2967/jnumed.124.268023
Hossein Jadvar, Amir Iravani, Lisa Bodei, Jeremie Calais
{"title":"Challenges with <sup>177</sup>Lu-PSMA-617 Radiopharmaceutical Therapy in Clinical Practice.","authors":"Hossein Jadvar, Amir Iravani, Lisa Bodei, Jeremie Calais","doi":"10.2967/jnumed.124.268023","DOIUrl":"https://doi.org/10.2967/jnumed.124.268023","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142304908","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}