Floriane Barbry, Benjamin Chevalier, Amandine Beron, Georges Lion, Samuel Boury, Camille Marciniak, Clio Baillet, Christine Do Cao, Arnaud Jannin
{"title":"Redifferentiation of a RET-Fusion, Radioiodine-Refractory, Differentiated Thyroid Cancer with Selpercatinib: Flip-Flop Between [<sup>18</sup>F]FDG PET/CT and <sup>131</sup>I Posttreatment Scanning.","authors":"Floriane Barbry, Benjamin Chevalier, Amandine Beron, Georges Lion, Samuel Boury, Camille Marciniak, Clio Baillet, Christine Do Cao, Arnaud Jannin","doi":"10.2967/jnumed.124.268539","DOIUrl":"10.2967/jnumed.124.268539","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"330"},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019104","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}
{"title":"From Scientist to Analyst to Strategist: Aharon (Ronny) Gal Talks with Ken Herrmann and Johannes Czernin About Leadership in Multinational Pharma.","authors":"Aharon Ronny Gal, Ken Herrmann, Johannes Czernin","doi":"10.2967/jnumed.124.269177","DOIUrl":"10.2967/jnumed.124.269177","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"163-165"},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019102","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}
Daniel Gillett, Russell Senanayake, James MacFarlane, Waiel Bashari, August Palma, Lihua Hu, Ines Harper, Iosif A Mendichovszky, Gunnar Antoni, Per Hellman, Anders Sundin, Matthew Hird, István Boros, Morris J Brown, Heok Cheow, Luigi Aloj, Franklin Aigbirhio, Mark Gurnell
{"title":"A Phase I/IIa Clinical Trial to Evaluate Safety and Adrenal Uptake of Para-Chloro-2-[<sup>18</sup>F]Fluoroethyletomidate in Healthy Volunteers and Patients with Primary Aldosteronism.","authors":"Daniel Gillett, Russell Senanayake, James MacFarlane, Waiel Bashari, August Palma, Lihua Hu, Ines Harper, Iosif A Mendichovszky, Gunnar Antoni, Per Hellman, Anders Sundin, Matthew Hird, István Boros, Morris J Brown, Heok Cheow, Luigi Aloj, Franklin Aigbirhio, Mark Gurnell","doi":"10.2967/jnumed.124.268425","DOIUrl":"https://doi.org/10.2967/jnumed.124.268425","url":null,"abstract":"<p><p>Primary aldosteronism (PA) is a common, potentially reversible, cause of hypertension. Distinguishing unilateral from bilateral PA is critical when deciding who should be offered surgery (unilateral adrenalectomy). Recent studies have shown that PET/CT with [<sup>11</sup>C]metomidate can accurately identify unilateral PA, with localization of the causative aldosterone-producing adenoma (APA). However, the availability of [<sup>11</sup>C]metomidate is limited to centers with an on-site cyclotron. Here, we report an early-phase human study with the <sup>18</sup>F-labeled analog, para-chloro-2-[<sup>18</sup>F]fluoroethyletomidate ([<sup>18</sup>F]CETO). <b>Methods:</b> We conducted a phase I/IIa, single-center, open-label, microdosing study. The primary objective was to evaluate the safety of up to 2 administrations of [<sup>18</sup>F]CETO in 6 patients with PA (3 unilateral disease, 3 bilateral disease) and 5 healthy volunteers. Safety evaluation included assessment of adrenal function after the first [<sup>18</sup>F]CETO administration. The biodistribution of [<sup>18</sup>F]CETO was assessed in a 90-min dynamic PET acquisition. In patients with PA, the effect of pretreatment with oral dexamethasone on [<sup>18</sup>F]CETO uptake by normal adrenal tissue and APAs was also assessed. <b>Results:</b> Eleven participants were recruited to the trial, including 6 patients and 5 healthy volunteers. No subjects experienced serious adverse events or reactions, and all participants had normal adrenal function after [<sup>18</sup>F]CETO administration. [<sup>18</sup>F]CETO demonstrated high selectivity for the adrenal glands with low uptake in other tissues. Visualization of APAs was enhanced after dexamethasone pretreatment, which suppressed [<sup>18</sup>F]CETO uptake by normal adrenal tissue. <b>Conclusion:</b> [<sup>18</sup>F]CETO is a safe radiopharmaceutical for PET imaging of the adrenal glands, with no observed adverse reactions or impairment of adrenal function in this study. [<sup>18</sup>F]CETO demonstrates selective high affinity for adrenal tissue, particularly APAs. Distinction between APAs and normal adrenal tissue is enhanced by dexamethasone pretreatment to suppress [<sup>18</sup>F]CETO uptake by normal glands. This positions [<sup>18</sup>F]CETO as a promising imaging tool for evaluation in the context of PA.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070449","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}
{"title":"CD38-Targeted <sup>89</sup>Zr-DFO-Daratumumab PET of Myeloma: Immuno-PET Impacting Clinical Care.","authors":"Gary A Ulaner, Jason Lewis, Ola Landgren","doi":"10.2967/jnumed.124.269393","DOIUrl":"https://doi.org/10.2967/jnumed.124.269393","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070466","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}
{"title":"China's Innovations in Nuclear Medicine: Global Insights into Clinical Advancements and Impact.","authors":"Xun Wang, Yifan Dong, Shuo Zhang","doi":"10.2967/jnumed.124.269185","DOIUrl":"https://doi.org/10.2967/jnumed.124.269185","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070509","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}
Isabelle Miederer, Hans-Georg Buchholz, Lena Rademacher, Cindy Eckart, Dominik Kraft, Markus Piel, Christian J Fiebach, Mathias Schreckenberger
{"title":"Dopaminergic Mechanisms of Cognitive Flexibility: An [<sup>18</sup>F]Fallypride PET Study.","authors":"Isabelle Miederer, Hans-Georg Buchholz, Lena Rademacher, Cindy Eckart, Dominik Kraft, Markus Piel, Christian J Fiebach, Mathias Schreckenberger","doi":"10.2967/jnumed.124.268317","DOIUrl":"https://doi.org/10.2967/jnumed.124.268317","url":null,"abstract":"<p><p>Cognitive flexibility is the ability to appropriately adapt one's thinking and behavior to changing environmental demands and is conceptualized as an aspect of executive function. The dopamine system has been implicated in cognitive flexibility; however, a direct, that is, neurochemical, link to cognitive flexibility has not been shown yet. The aim of this study was, therefore, to investigate how cognitive flexibility is mediated by dopaminergic signaling in the ventromedial prefrontal cortex (vmPFC). <b>Methods:</b> Eighteen participants were measured in a PET study with 174 ± 12 MBq of the D<sub>2/3</sub> receptor ligand [<sup>18</sup>F]fallypride in a block design with 2 parts. While participants processed 2 tasks sequentially without rule switching on a computer screen in the first part of the PET scan, they had to flexibly switch between the 2 task rules after 100 min after injection in the second part. Dopamine release (γ) was quantified using the linearized simplified reference region model contrasting the 2 task blocks (switching vs. no-switching/baseline). <b>Results:</b> The statistical analysis of the parametric γ-images showed that the increased cognitive demand during task switching induced a displacement of the D<sub>2/3</sub> receptor ligand [<sup>18</sup>F]fallypride in the vmPFC (maximum T value = 13.8; cluster size: 528 voxels; familywise error rate-corrected <i>P</i> < 0.001; mean γ = 0.022 ± 0.006 min<sup>-1</sup>). Furthermore, a correlation between behavioral switch costs and vmPFC [<sup>18</sup>F]fallypride displacement suggested that participants showing greater dopamine release were more efficient in task switching. <b>Conclusion:</b> To our knowledge, this is the first experimental PET study to show direct involvement of dopamine in the vmPFC in a task-switching paradigm, confirming model assumptions about the neurochemical basis of cognitive flexibility.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070518","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}
Harry Marquis, C Ross Schmidtlein, Robin de Nijs, Pablo Mínguez Gabiña, Johan Gustafsson, Gunjan Kayal, Juan C Ocampo Ramos, Lukas M Carter, Dale L Bailey, Adam L Kesner
{"title":"MIRD Pamphlet No. 32: A MIRD Recovery Coefficient Model for Resolution Characterization and Shape-Specific Partial-Volume Correction.","authors":"Harry Marquis, C Ross Schmidtlein, Robin de Nijs, Pablo Mínguez Gabiña, Johan Gustafsson, Gunjan Kayal, Juan C Ocampo Ramos, Lukas M Carter, Dale L Bailey, Adam L Kesner","doi":"10.2967/jnumed.124.268520","DOIUrl":"https://doi.org/10.2967/jnumed.124.268520","url":null,"abstract":"<p><p>Accurate quantification in emission tomography is essential for internal radiopharmaceutical therapy dosimetry. Mean activity concentration measurements in objects with diameters less than 10 times the full width at half maximum of the imaging system's spatial resolution are significantly affected (>10%) by the partial-volume effect. This study develops a framework for PET and SPECT spatial resolution characterization and proposes 2 MIRD recovery coefficient models-a geometric mean approximation (RECOVER-GM) and an empirical model (RECOVER-EM)-that provide shape-specific partial-volume correction (PVC). The models were validated using simulations and phantom experiments, with a comparative PVC test on ellipsoidal phantoms demonstrating that the RECOVER models significantly reduced error in activity quantification by factors of approximately 1.3-5.7 compared with conventional sphere-based corrections. The proposed recovery coefficient models and PVC methodology provide a robust framework for improved region-based PVC, including corrections for nonspherical tumor volumes. This work is part of the ongoing MIRDsoft.org project that aims to enhance accessibility to advanced dosimetry tools for improved disease characterization, treatment planning, and radiopharmaceutical therapy dosimetry.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070524","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}
{"title":"The PRIMARY Score: Present and Future.","authors":"Linlin Guo, Guohua Shen","doi":"10.2967/jnumed.124.267898","DOIUrl":"https://doi.org/10.2967/jnumed.124.267898","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070538","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}
Cameron N Johnstone, Laura D Osellame, Zhipeng Cao, Alexander F McDonald, Angela Rigopoulos, Ingrid J G Burvenich, Christian W Wichmann, Nancy Guo, Alesia N Ivashkevich, Michael P Wheatcroft, Edwin B Yan, Astrid Zimmermann, Frank T Zenke, Christian Sirrenberg, Fiona E Scott, Andrew M Scott
{"title":"DNA-Dependent Protein Kinase Inhibitor Peposertib Enhances Efficacy of <sup>177</sup>Lu-Based Radioimmunotherapy in Preclinical Models of Prostate and Renal Cell Carcinoma.","authors":"Cameron N Johnstone, Laura D Osellame, Zhipeng Cao, Alexander F McDonald, Angela Rigopoulos, Ingrid J G Burvenich, Christian W Wichmann, Nancy Guo, Alesia N Ivashkevich, Michael P Wheatcroft, Edwin B Yan, Astrid Zimmermann, Frank T Zenke, Christian Sirrenberg, Fiona E Scott, Andrew M Scott","doi":"10.2967/jnumed.124.268695","DOIUrl":"https://doi.org/10.2967/jnumed.124.268695","url":null,"abstract":"<p><p>Novel radiation sensitizers, including inhibitors targeting DNA damage response, have been developed to enhance the efficacy of anticancer treatments that induce DNA damage in cancer cells. Peposertib, a potent, selective, and orally administered inhibitor of DNA-dependent protein kinase, impedes the nonhomologous end-joining mechanism for DNA double-strand break (DSB) repair. We investigated radioimmunotherapy alone or with peposertib in preclinical models of renal cell carcinoma (RCC) or prostate cancer. <b>Methods:</b> <sup>177</sup>Lu-DOTA-girentuximab (targeting carbonic anhydrase IX) or <sup>177</sup>Lu-DOTA-rosopatamab (targeting prostate-specific membrane antigen) was used to deliver β-radiation to tumors via a single intravenous dose (3 or 6 MBq) in mice bearing SK-RC-52 RCC or LNCaP prostate cancer xenografts, respectively. Peposertib (50 mg/kg daily for 14 d) was administered via oral gavage. Biodistribution and in vivo imaging of <sup>177</sup>Lu-based radioimmunotherapy were performed for both preclinical models. Tumor growth and body weight were monitored until the endpoint. Assessment of DNA damage was performed by measuring DSBs through analysis of γH2AX foci formation in tumor sections. <b>Results:</b> Ex vivo biodistribution and in vivo SPECT/MRI revealed excellent tumor uptake of each radiopharmaceutical. Mouse body weight was stable in all treatment arms. Peposertib alone did not show a significant antitumor effect. The addition of peposertib to <sup>177</sup>Lu-DOTA-girentuximab showed enhanced antitumor efficacy compared with <sup>177</sup>Lu-DOTA-girentuximab alone in the SK-RC-52 animal model, with a 4 of 4 complete response rate in the <sup>177</sup>Lu-DOTA-girentuximab (6 MBq) plus peposertib arm. Peposertib combined with low-dose <sup>177</sup>Lu-DOTA-girentuximab (3 MBq) demonstrated antitumor activity comparable to <sup>177</sup>Lu-DOTA-girentuximab (6 MBq) monotherapy. In the LNCaP prostate cancer model, the combination of <sup>177</sup>Lu-DOTA-rosopatamab (6 MBq) and peposertib achieved a 3 of 4 complete response rate. Increased DSBs were observed with the addition of peposertib to <sup>177</sup>Lu-based radioimmunotherapy. <b>Conclusion:</b> The combination of peposertib with <sup>177</sup>Lu-based radioimmunotherapy was well tolerated in preclinical models of RCC and prostate cancer. Our findings suggest a synergistic effect between peposertib and <sup>177</sup>Lu-based radioimmunotherapy, wherein peposertib enhanced the efficacy of radioimmunotherapy. This synergy indicates the potential to reduce the necessary dose of radioimmunotherapy for effective cancer treatment.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070515","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}
{"title":"Reply: On Facilitating the End of the Linear No-Threshold Era.","authors":"Mohan Doss","doi":"10.2967/jnumed.124.269292","DOIUrl":"https://doi.org/10.2967/jnumed.124.269292","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070529","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}