{"title":"Reply: On Facilitating the End of the Linear No-Threshold Era.","authors":"Mohan Doss","doi":"10.2967/jnumed.124.269292","DOIUrl":"10.2967/jnumed.124.269292","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"483-484"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","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}
{"title":"A Comment on \"Effectiveness and Patient Experiences of Rhenium Skin Cancer Therapy for Nonmelanoma Skin Cancer: Interim Results from the EPIC-Skin Study\".","authors":"Miranda Wallace, Jim Muir","doi":"10.2967/jnumed.124.269058","DOIUrl":"10.2967/jnumed.124.269058","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"484-485"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416629","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}
Li Sun, Yuyun Sun, Ke Zuo, Lei Fan, Xiao Wang, Jianping Zhang, Silong Hu, Xiaosheng Liu, Jindian Li, Ye Li, Zhiming Shao, Xiaoping Xu, Aiguo Wu, Shaoli Song
{"title":"Pilot Study of Nectin-4-Targeted PET Imaging Agent <sup>68</sup>Ga-FZ-NR-1 in Triple-Negative Breast Cancer from Bench to First-in-Human.","authors":"Li Sun, Yuyun Sun, Ke Zuo, Lei Fan, Xiao Wang, Jianping Zhang, Silong Hu, Xiaosheng Liu, Jindian Li, Ye Li, Zhiming Shao, Xiaoping Xu, Aiguo Wu, Shaoli Song","doi":"10.2967/jnumed.124.269024","DOIUrl":"10.2967/jnumed.124.269024","url":null,"abstract":"<p><p>Nectin cell adhesion molecule 4 (Nectin-4) is an emerging biomarker for cancer diagnosis and therapy. We developed a Nectin-4-targeted <sup>68</sup>Ga-DOTA-Sar10-Nectin-4 (<sup>68</sup>Ga-FZ-NR-1) PET/CT radiotracer for detecting Nectin-4 expression in a tumor model and in triple-negative breast cancer (TNBC) patients. <b>Methods:</b> A series of Nectin-4-targeted radiotracers-<sup>68</sup>Ga-FZ-NR-1, <sup>68</sup>Ga-DOTA-polyethylene glycol 5-Nectin-4 (<sup>68</sup>Ga-FZ-NR-2), and <sup>68</sup>Ga-DOTA-polyethylene glycol 10-Nectin-4 (<sup>68</sup>Ga-FZ-NR-3)-were synthesized, and their targeting ability and specificity were evaluated in vitro and in vivo. In vitro experiments were performed in the MDA-MB-468 (Nectin-4-positive) and MDA-MB-231 (Nectin-4-negative) cell lines. PET/CT imaging in tumor models was performed to assess the Nectin-4-targeting ability of the radiotracers. After preclinical experiments and screening, the <sup>68</sup>Ga-FZ-NR-1 radiotracer was selected for safety and efficacy evaluation in a first-in-human trial in TNBC patients. Positive lesions were biopsied and analyzed by immunohistochemistry to determine Nectin-4 expression levels. <b>Results:</b> The 3 <sup>68</sup>Ga-labeled radiotracers exhibited high radiochemical purity, stability, and strong affinity for Nectin-4. In vitro cell uptake studies showed that the radiotracers effectively targeted Nectin-4 in MDA-MB-468 cells, and <sup>68</sup>Ga-FZ-NR-1 showed the highest targeting efficacy. In the MDA-MB-468 tumor model, PET/CT imaging showed that <sup>68</sup>Ga-FZ-NR-1 was taken up at higher rates than <sup>68</sup>Ga-FZ-NR-2 and <sup>68</sup>Ga-FZ-NR-3, and it exhibited favorable pharmacokinetics and safety profiles. <sup>68</sup>Ga-FZ-NR-1 was thus selected for subsequent clinical trials. <sup>68</sup>Ga-FZ-NR-1 PET/CT effectively identified tumors in 9 patients with TNBC, which was confirmed by <sup>18</sup>F-FDG PET/CT. Biopsy samples of the tumor lesions revealed that the positive lesions identified by <sup>68</sup>Ga-FZ-NR-1 PET/CT corresponded to areas of high Nectin-4 expression. <b>Conclusion:</b> A series of Nectin-4-targeted radiotracers (<sup>68</sup>Ga-FZ-NR-1, <sup>68</sup>Ga-FZ-NR-2, and <sup>68</sup>Ga-FZ-NR-3) was developed and evaluated. Preclinical studies demonstrated that <sup>68</sup>Ga-FZ-NR-1 can identify tumors with high Nectin-4 expression. In a preliminary clinical study, <sup>68</sup>Ga-FZ-NR-1 was used to effectively identify and visualize Nectin-4-expressing tumor lesions in patients with TNBC, which was confirmed by immunohistochemistry. This radiotracer provides a noninvasive approach to the assessment of Nectin-4 and a potential basis for the development of Nectin-4-targeted treatments for TNBC.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"473-479"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416622","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":"Erratum.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":"66 3","pages":"481"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143545472","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}
Janet Eary, Jeanne Link, David Mankoff, David Vera, Tom Ruth
{"title":"Kenneth A. Krohn, PhD, 1945-2024.","authors":"Janet Eary, Jeanne Link, David Mankoff, David Vera, Tom Ruth","doi":"10.2967/jnumed.124.269449","DOIUrl":"10.2967/jnumed.124.269449","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"486"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070521","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":"On Facilitating the End of the Linear No-Threshold Era.","authors":"Eduardo Galiano","doi":"10.2967/jnumed.124.269042","DOIUrl":"10.2967/jnumed.124.269042","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"483"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070527","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":"<sup>68</sup>Ga-FAPI-04 PET/CT Imaging for Assessing Renal Tubulointerstitial Fibrosis in Lupus Nephritis.","authors":"Shuyi Yu, Zhixia Yang, Zetao Ding, Yingqi Jia, Liyan Wan, Lei Li, Jing Lv, Haoyu Pan, Jinyi Qian, Xiaohan Wei, Yue Yang, Yunlong Zan, Jialin Teng, Biao Li, Chengde Yang, Jing Xu, Luan Xue, Hui Shi, Min Zhang","doi":"10.2967/jnumed.124.268643","DOIUrl":"10.2967/jnumed.124.268643","url":null,"abstract":"<p><p>The objective of this study was to evaluate the feasibility of using <sup>68</sup>Ga-labeled fibroblast activation protein inhibitor-04 (<sup>68</sup>Ga-FAPI-04) PET/CT imaging as a molecular tracer and noninvasive tool for assessing active renal tubulointerstitial fibrosis in patients with lupus nephritis (LN). <b>Methods:</b> The study included 29 LN patients who underwent <sup>68</sup>Ga-FAPI-04 PET/CT scanning to quantify <sup>68</sup>Ga-FAPI-04 uptake. Renal biopsies were performed within a week of scanning. Renal fibrosis levels in biopsy samples were assessed by Masson staining. Immunofluorescence analysis identified the expression of fibroblast activation protein (FAP), E-cadherin, and α-smooth muscle actin in the renal biopsy specimens. FAP expression of healthy controls, LN patients, and patients with minimal change of disease at the messenger RNA level and its association with interferon levels were explored using microarray data from the Gene Expression Omnibus database. Additionally, quantitative polymerase chain reaction and Western blot analyses quantified FAP messenger RNA and protein expression in renal tubular epithelial cells (RTEC) after stimulation with interferon-α in vitro. <b>Results:</b> The study revealed significantly increased renal <sup>68</sup>Ga-FAPI-04 uptake in LN patients (<i>n</i> = 29) compared with healthy controls (<i>n</i> = 26). Normalized renal <sup>68</sup>Ga-FAPI-04 uptake positively correlated with disease duration, creatinine levels, chronicity index, and renal tubulointerstitial fibrosis levels. Patients with a chronicity index exceeding 4, indicative of a poorer prognosis, showed markedly higher renal <sup>68</sup>Ga-FAPI-04 uptake. FAP expression was predominantly localized in RTEC, where increased FAP expression corresponded to reduced E-cadherin expression. Gene set enrichment analysis of GSE112943 and GSE60861 datasets showed positive enrichment of type I interferon signaling gene sets (<i>P</i> < 0.01). Correlation analysis of interferon-α and interferon-γ pathways with FAP expression in these datasets was significant (<i>P</i> < 0.01). In vitro experiments, with interferon-α-stimulated RTEC showed elevated FAP expression. <b>Conclusion:</b> This study demonstrates the feasibility of using <sup>68</sup>Ga-FAPI-04 PET/CT imaging for noninvasive assessment of active lupus renal tubulointerstitial fibrosis. Elevated FAP expression in LN is primarily expressed by RTEC and contributes to the development of interstitial fibrosis. Type I interferon appears to induce FAP expression. These findings provide insights into the molecular mechanisms underlying renal tubulointerstitial fibrosis in LN and offer a valuable tool for assessing kidney status in lupus.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"418-424"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416628","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}
Amal Saidi, Tania A Stallons, Amy G Wong, Aaron T Schatzmann, Ugur Soysal, Julien J Torgue
{"title":"Side-by-Side Comparison of the In Vivo Performance of [<sup>212</sup>Pb]Pb-DOTAMTATE and Other SSTR2-Targeting Compounds.","authors":"Amal Saidi, Tania A Stallons, Amy G Wong, Aaron T Schatzmann, Ugur Soysal, Julien J Torgue","doi":"10.2967/jnumed.124.268345","DOIUrl":"10.2967/jnumed.124.268345","url":null,"abstract":"<p><p>There are numerous versions of octreotide and octreotate, including DOTAMTATE, DOTATATE, JR11, and lead-specific chelator (PSC)-PEG2-TOC. These peptides, which can be either analogs or antagonists, are used in nuclear medicine for diagnostic imaging or targeted radionuclide therapy of neuroendocrine tumors that are positive for somatostatin receptors (SSTRs). Despite their structural and targeting similarities, they have distinct properties and clinical uses. We aimed to perform an extensive preclinical comparison of all these somatostatin analogs with <sup>212</sup>Pb, directly studying their pharmacokinetic properties in tumors overexpressing SSTR2. <b>Methods:</b> All SSTR2 analogs were manufactured with the DOTAM, PSC, or DOTA chelators for appropriate comparison after radiolabeling with <sup>212</sup>Pb. Chelation, quantification, and pharmacokinetics were compared side by side in AR42J-tumor-bearing animals. <b>Results:</b> These findings highlight the superior chelation efficiency and faster kinetics of DOTAM and then DOTA compared with the PSC. We also discovered a superior tumor-to-kidney area under the curve ratio for [<sup>212</sup>Pb]Pb-DOTAMTATE over other SSTR2-targeting peptides when radiolabeled with <sup>212</sup>Pb. <b>Conclusion:</b> Taken together, the results indicates that [<sup>212</sup>Pb]Pb-DOTAMTATE has favorable tumor retention and a more favorable dosimetry profile, which is crucial for targeted α-therapy in treating SSTR2-positive neuroendocrine tumors.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"391-397"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070533","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}
Johannes Czernin, Lisa Bodei, Irvin Modlin, Jeremie Calais
{"title":"Reflections on the Demand for PSMA- and SSTR-Targeted Radiopharmaceutical Therapies: Why We Were Wrong (and Why We Will Be Right Eventually).","authors":"Johannes Czernin, Lisa Bodei, Irvin Modlin, Jeremie Calais","doi":"10.2967/jnumed.124.269401","DOIUrl":"10.2967/jnumed.124.269401","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"333-336"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367158","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":"SPECT Deserves RESPECT: The Potential of SPECT/CT to Optimize Patient Outcomes with Theranostics Therapy.","authors":"Louise Emmett","doi":"10.2967/jnumed.124.268325","DOIUrl":"10.2967/jnumed.124.268325","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"349-350"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924242","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}