Journal of nuclear medicine : official publication, Society of Nuclear Medicine最新文献

{"title":"Theranostic Approach Using Radioiodinated Trimethoprim Targeting <i>E. coli</i> Dihydrofolate Reductase in Engineered Cells.","authors":"Nitika Sharma, Swarbhanu Sarkar, Jean M Etersque, Kimberly J Edwards, Jonathan M Pham, Kexiang Xu, Joshua Scheuermann, Tommy Nguyen, Andrew Ruff, Paul Martorano, Justin D Northrup, Katheryn Lohith, Hsiaoju S Lee, Michael D Farwell, Daniel Pryma, Mark A Sellmyer","doi":"10.2967/jnumed.126.272322","DOIUrl":"10.2967/jnumed.126.272322","url":null,"abstract":"<p><p>Radiopharmaceutical therapy (RPT) has re-emerged as a potent approach for targeting tumors, particularly for the treatment of neuroendocrine tumors and prostate cancer expressing the somatostatin and prostate-specific membrane antigen receptors, respectively. In addition to endogenously expressed proteins specific for these cancers, RPT has been explored using synthetic, engineered expression of proteins in tumor tissues. An early example of this was the use of sodium iodide symporter delivered to tumors using viral vectors, which were subsequently treated with [¹³¹I]NaI. This approach is complicated by the natural uptake in human tissues that express sodium iodide symporter (e.g., the thyroid). However, given the rapid acceleration of gene and cell therapies, expansion and re-exploration of the synthetic, genetically engineered RPT paradigm is warranted. This is especially true for RPT, which can be coupled with PET companion imaging agents. <b>Methods:</b> Here, we developed a β-emitter radiotherapeutic probe, radioiodinated trimethoprim ([¹³¹I]I-TMP), and evaluated its therapeutic potential. In addition, we developed [^124/125I]I-TMP radiotracers for uptake and imaging studies. The selective cytotoxicity of [¹³¹I]I-TMP toward <i>E. coli</i> dihydrofolate reductase (eDHFR)-expressing cells was evaluated using time- and dose-dependent responses. Biodistribution was characterized in healthy mice followed by small-animal PET/CT studies using a tumor xenograft model and [¹²⁴I]I-TMP. Finally, the eDHFR synthetic RPT approach was applied in murine cancer models to evaluate its cytotoxicity in tumors. <b>Results:</b> Radioiodinated trimethoprim radiotracers ([^131/125/124I]I-TMP) exhibited selective uptake in eDHFR-positive tumors both in vitro and in vivo. Small-animal imaging with [¹²⁴I]I-TMP demonstrated specific retention in I45-eDHFR tumors with negligible background signals. A dose-dependent and time-dependent cytotoxic effect was observed selectively in eDHFR cell lines. Furthermore, targeted treatment with [¹³¹I]I-TMP led to a significant reduction in tumor volume expressing eDHFR compared with wild-type tumors or untreated controls. <b>Conclusion:</b> This synthetic RPT approach shows promise for future applications in targeted cancer therapies and genetic medicine, particularly in the realm of theranostic strategies that integrate trimethoprim-based companion imaging and radiotherapy for the treatment of cancer.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1627-1634"},"PeriodicalIF":9.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687380","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 to \"High Quantitative Accuracy Is Possible with ¹⁷⁷Lu SPECT\".","authors":"Bella Salerno, Mercy Akerele, Daniel L J Thorek","doi":"10.2967/jnumed.126.272772","DOIUrl":"10.2967/jnumed.126.272772","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1685-1686"},"PeriodicalIF":9.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148762341","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}

{"title":"Recombinant Human Thyrotropin Versus Thyroid Hormone Withdrawal for Radioactive Iodine Therapy in Metastatic Differentiated Thyroid Cancer: A Multicenter Retrospective Study.","authors":"Chae Moon Hong, Joonhyung Gil, Gi Jeong Cheon, Jae-Hoon Lee, Keunyoung Kim, Yeon-Hee Han, Jahae Kim, Ho-Chun Song, So Won Oh, Myoung Hyoun Kim, Jung Mi Park, Ari Chong, Hye-Kyung Shim, Yukyung Lee, Seong-Young Kwon","doi":"10.2967/jnumed.126.273112","DOIUrl":"https://doi.org/10.2967/jnumed.126.273112","url":null,"abstract":"<p><p>This study compared clinical and safety outcomes of radioactive iodine therapies administered after thyroid hormone withdrawal (THW) versus recombinant human thyrotropin (rhTSH) in patients with differentiated thyroid cancer and distant metastases, using both patient- and therapy-based analyses. <b>Methods:</b> Patient-based analyses included 352 patients classified into the THW-only (<i>n</i> = 259), rhTSH-only (<i>n</i> = 40), or mixed (<i>n</i> = 53) groups, whereas therapy-based analyses included 564 radioactive iodine therapies administered after THW (<i>n</i> = 459) or rhTSH (<i>n</i> = 105). Overall survival and disease-specific survival were assessed at the patient level, whereas imaging-based response, change in thyroglobulin after therapy (biochemical response), and laboratory-based safety outcomes were evaluated at the therapy level. <b>Results:</b> Overall survival and disease-specific survival did not differ significantly among the 3 patient groups (all <i>P</i> > 0.25). Imaging- and biochemical-response outcomes also were comparable between groups who received RAI therapy after THW and rhTSH (both <i>P</i> > 0.05), and the preparation method was not significantly associated with either response outcome. In contrast, liver function abnormalities and the occurrence of at least 1 prespecified laboratory-based safety outcome were significantly more frequent after THW (both <i>P</i> < 0.001). <b>Conclusion:</b> rhTSH and THW were associated with comparable survival and treatment responses in patients with differentiated thyroid cancer with distant metastases, whereas laboratory-based safety outcomes were more frequent after THW preparation. These findings strengthen multicenter real-world evidence supporting rhTSH as an alternative to THW for select patients, particularly when minimizing prolonged hypothyroidism is important for individualized treatment planning.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043022","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":"Next-Generation Peptide Receptor Radionuclide Therapy: A Phase 1 Dose-Escalation and Dosimetry Study of ¹⁷⁷Lu-DOTA-EB-TATE.","authors":"Lisa Bodei, Pat Zanzonico, Simone Krebs, Diane Reidy-Lagunes, Nitya Raj, Serge K Lyashchenko, Jason S Lewis, Heiko Schöder, Joseph A O'Donoghue","doi":"10.2967/jnumed.126.272756","DOIUrl":"https://doi.org/10.2967/jnumed.126.272756","url":null,"abstract":"<p><p>Neuroendocrine tumors (NETs) are often detected late, limiting curative treatments and requiring systemic therapies such as peptide receptor radionuclide therapy (PRRT). Although ¹⁷⁷Lu-DOTATATE has demonstrated efficacy, its rapid clearance from the circulation limits tumor radiation delivery and may increase renal toxicity risk. ¹⁷⁷Lu-DOTA-EB-TATE, a novel PRRT agent conjugated with Evans blue for albumin binding, offers extended circulation time and enhanced tumor uptake, potentially improving therapeutic outcomes. This phase 1 study aimed to evaluate the safety, dosimetry, and preliminary efficacy of ¹⁷⁷Lu-DOTA-EB-TATE in patients with advanced gastroenteropancreatic NETs. <b>Methods:</b> Six adults with inoperable, measurable gastroenteropancreatic NETs (WHO grades 2 and 3) and with somatostatin receptor overexpression were enrolled. Using a 3 + 3 dose-escalation design, patients received ¹⁷⁷Lu-DOTA-EB-TATE at nominal activities of 1.85, 3.70, or 5.55 GBq intravenously for 2 cycles, 6 wk apart. Individualized dosimetry after the first cycle informed subsequent treatment delivery. Safety was assessed biweekly, and tumor responses were evaluated using RECIST at 3 and 6 mo. <b>Results:</b> Treatment was well-tolerated, with mild side effects, including nausea, fatigue, and hair loss; no renal toxicity occurred. The median kidney absorbed dose per cycle was 4.8 Gy (range, 2.9-8.9 Gy; mean, 2.2 Gy/GBq). Hematologic toxicity was dose-limiting, with persistent grade 3 febrile neutropenia observed at 3.7 GBq in 1 patient and confirmed in an external cohort. Thus, the maximum tolerated activity was set at 3.70 GBq and the recommended phase 2 activity at 1.85 GBq per cycle to avoid irreversible marrow suppression. Tumor responses included stable disease (<i>n</i> = 5) and partial response (<i>n</i> = 1) at 3 mo; disease progressed in 2 patients at 6 mo after treatment completion. <b>Conclusion:</b> The 2-cycle regimen of ¹⁷⁷Lu-DOTA-EB-TATE delivered higher renal absorbed doses compared with standard ¹⁷⁷Lu-DOTATATE. With individualized dosimetry, no kidney toxicity was observed. However, increased retention in the circulation caused hematologic-related side effects and made marrow the dose-limiting organ. Within the defined dosing limits of this study, ¹⁷⁷Lu-DOTA-EB-TATE is a potential high-uptake alternative to standard PRRT, supporting a shortened 2-cycle schedule for earlier response assessment. Further research should refine dosing schedules and patient selection to balance efficacy and safety.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043053","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":"Imaging the Cancer Metabolome.","authors":"Chaitanya Divgi","doi":"10.2967/jnumed.126.272443","DOIUrl":"https://doi.org/10.2967/jnumed.126.272443","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043024","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":"Phase 1 Dose-Escalation Study of the Rapid-Clearance Radioligand [¹⁷⁷Lu]Lu-P17-087 in Metastatic Castration-Resistant Prostate Cancer: Dosimetry, Safety, and Preliminary Efficacy.","authors":"Ruiyue Zhao, Mingzhao Li, Jie Lv, Jing Zhang, Huizhen Zhong, Yimin Fu, Jinhui Liu, Di Gu, Guohua Zeng, Hank F Kung, Lin Zhu, Jinkun Huang, Xinlu Wang","doi":"10.2967/jnumed.126.272406","DOIUrl":"https://doi.org/10.2967/jnumed.126.272406","url":null,"abstract":"<p><p>Given the rapid systemic clearance and favorable kinetic profile of the novel DOTA(GA)₂-conjugated ligand [¹⁷⁷Lu]Lu-P17-087, this phase 1 study aimed to systematically evaluate the safety, pharmacokinetics, dosimetry, and preliminary antitumor activity of escalating therapeutic activities in patients with metastatic castration-resistant prostate cancer (mCRPC). <b>Methods:</b> Nine patients with progressive mCRPC and high prostate-specific membrane antigen (PSMA) expression on PET/CT were enrolled. An adaptive intrapatient dose-escalation protocol was used, with administered activities categorized as low (1.1-2.3 GBq), mid (3.7-5.6 GBq), and high (∼7.4 GBq). Serial whole-body planar scintigraphy (1-96 h postinjection) and quantitative SPECT/CT (24 h postinjection) were acquired for dosimetry analysis using OLINDA/EXM. Safety was assessed per Common Terminology Criteria for Adverse Events version 5.0. Antitumor efficacy was evaluated by prostate-specific antigen (PSA) response and radiographic response using PSMA PET/CT (RECIP 1.0). Activity-associated PSA changes were summarized descriptively across administered activity levels. <b>Results:</b> [¹⁷⁷Lu]Lu-P17-087 exhibited rapid pharmacokinetics (effective half-life of 0.52 h in blood). This fast-clearance profile yielded low absorbed doses to dose-limiting organs, including the kidneys (0.39 ± 0.26 Gy/GBq) and red marrow (0.07 ± 0.01 Gy/GBq). Conversely, lesions showed sustained retention, particularly in lymph node metastases (half-life, 22.9 h). The dose-escalation regimen was well tolerated; no dose-limiting toxicities or grade 3/4 hematologic adverse events were observed, even at the maximum administered activity of 7.4 GBq. Biochemical response was observed in most patients, with 8 of 9 (88.9%) demonstrating a decline in PSA levels from baseline. A 50% decline from baseline in PSA was achieved in 2 of 9 patients (22.2%). The magnitude of PSA reduction varied across administered activity levels. <b>Conclusion:</b> This phase 1 dose-escalation study showed rapid in vivo clearance of [¹⁷⁷Lu]Lu-P17-087 and low early normal-organ toxicity in this small cohort. Administration of activities up to 7.4 GBq per cycle was feasible and was associated with preliminary antitumor activity. Larger studies with longer follow-up are required to define efficacy, safety, and the optimal dosing strategy.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043077","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":"Optimizing the Therapeutic Index: Sequential Intraarterial-Intravenous PRRT with Personalized Volumetric-Adjusted Dosing.","authors":"Lisa Bodei, Etay Ziv, Audrey Mauguen, Pat Zanzonico, Diane Reidy, Adrian Gonzalez-Aguirre, Bae Chu, Jonathan Kuten, Nitya Raj, Heiko Schöder, Joseph A O'Donoghue","doi":"10.2967/jnumed.126.272710","DOIUrl":"https://doi.org/10.2967/jnumed.126.272710","url":null,"abstract":"<p><p>Patients with well-differentiated neuroendocrine tumors (NETs) frequently present with liver-dominant metastases, which significantly impact prognosis and limit curative options. Although standard intravenous peptide receptor radionuclide therapy with ¹⁷⁷Lu-DOTATATE is effective, strategies to intensify the radiation dose to hepatic lesions are needed to improve outcomes. This prospective clinical trial investigated the feasibility, tolerability, and preliminary efficacy of a personalized treatment schedule combining intraarterial and intravenous administrations of ¹⁷⁷Lu-DOTATATE. <b>Methods:</b> Ten consecutive adults with progressive, nonresectable, liver-dominant metastatic gastroenteropancreatic NETs expressing somatostatin receptors were enrolled. The treatment protocol comprised 4 cycles of ¹⁷⁷Lu-DOTATATE administered every 2 mo (2 initial intraarterial cycles followed by 2 intravenous cycles). Intraarterial administration involved angiographically guided, selective catheterization of the hepatic arteries with volumetrically adjusted activity to maximize targeted delivery. Safety monitoring, radiation protection, and dosimetry comparisons between intraarterial and intravenous routes were performed. <b>Results:</b> The intraarterial administration procedure was feasible in 100% of patients. Radiation exposure to staff and patients remained within regulatory limits, with no contamination events. Dosimetry analysis indicated that intraarterial administration (cycle 1) delivered a greater than 3-fold higher radiation dose to liver metastases compared with the intravenous route (cycle 3), although interim response may have played a role. Furthermore, ⁶⁸Ga-DOTATATE PET imaging revealed an 86% increase in median liver lesion uptake with intraarterial administration. The regimen was generally well-tolerated, with only 1 severe adverse event reported (low esophageal tear), which was not attributed to the administration route. Efficacy analysis showed partial response rates in 67% of patients at the first follow-up 3 mo after treatment completion, improving to 87% at the second follow-up (6 mo) in accordance with RECIST and volumetric criteria. <b>Conclusion:</b> The sequential administration of intraarterial followed by intravenous ¹⁷⁷Lu-DOTATATE is a feasible and safe therapeutic strategy for liver-dominant metastatic NETs. The use of a personalized, volumetric-based approach provided higher uptake and absorbed doses in hepatic metastases, with high objective response rates and effectively maintained systemic coverage.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043044","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":"Association of <i>ATM</i> Alterations with Outcomes After ¹⁷⁷Lu-PSMA-617 Treatment in Patients with Metastatic Castration-Resistant Prostate Cancer.","authors":"Vikrant Mahajan, Lauren Yu, Lily Kollitz, Ella Boytim, Nicholas A Zorko, Ian J Okazaki, Zuzan Cayci, Scott M Dehm, Justin Hwang, Ali T Arafa, Emmanuel S Antonarakis","doi":"10.2967/jnumed.126.273055","DOIUrl":"https://doi.org/10.2967/jnumed.126.273055","url":null,"abstract":"<p><p>Treatment with ¹⁷⁷Lu-PSMA-617 improves survival in some patients with metastatic castration-resistant prostate cancer, yet marked heterogeneity in treatment response underscores the need for robust biomarkers. Homologous recombination repair (HRR) gene alterations are frequently analyzed in composite, potentially obscuring gene-level predictive signals. <b>Methods:</b> We conducted a retrospective genomic study of 205 patients with metastatic castration-resistant prostate cancer who received ¹⁷⁷Lu-PSMA-617 at the University of Minnesota between 2022 and 2026 and for whom next-generation DNA sequencing results were available. Clinical endpoints included a prostate-specific antigen (PSA) response (a reduction of at least 50% from baseline [PSA₅₀]), progression-free survival (PFS), and overall survival (OS). A random-effects pooled analysis of published studies reporting OS hazard ratios according to <i>ATM</i>, <i>TP53</i>, <i>CDK12</i>, <i>SPOP</i>, and <i>AR</i> alteration status was also performed. <b>Results:</b> <i>ATM</i> alterations (12.7%) were independently associated with improved PSA₅₀ response (odds ratio, 2.91; <i>P</i> = 0.009), longer PFS (hazard ratio [HR], 0.40; <i>P</i> = 0.002), and longer OS (HR, 0.39; <i>P</i> = 0.003). <i>BRCA2</i> alterations were not associated with clinical outcomes. <i>CDK12</i> alterations represented the strongest adverse genomic factor, conferring significantly shorter PFS (HR, 2.76; <i>P</i> = 0.013) and OS (HR, 2.58; <i>P</i> = 0.016). In the pooled analysis, <i>ATM</i> alterations remained significantly associated with improved OS (pooled HR, 0.36), whereas <i>TP53</i> (pooled HR, 1.49) and <i>AR</i> (pooled HR, 1.57) were associated with significantly worse OS. <b>Conclusion:</b> <i>ATM</i> alterations were independently associated with improved outcomes after treatment with ¹⁷⁷Lu-PSMA-617 and validated across a pooled analysis. Marked heterogeneity among individual HRR genes was observed, supporting gene-level rather than composite HRR analysis for precision oncology in radiopharmaceutical therapy.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043018","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":"Glypican-3 as a Theranostic Target in Hepatocellular Carcinoma.","authors":"Wolfgang A Weber, Matthias Eiber, Constantin Lapa, Ursula Ehmer","doi":"10.2967/jnumed.126.272814","DOIUrl":"https://doi.org/10.2967/jnumed.126.272814","url":null,"abstract":"<p><p>Glypican-3 (GPC3) has emerged as an attractive molecular target for the imaging and therapy of hepatocellular carcinoma (HCC). It is highly expressed in most tumors but shows no or minimal expression in the normal adult liver and cirrhosis. This expression profile has stimulated the parallel development of GPC3-directed antibodies, antibody-drug conjugates, cellular immunotherapies, molecular imaging agents, and therapeutic radiopharmaceuticals. Early clinical imaging studies with radiolabeled antibodies established proof of principle that GPC3 can be visualized with PET imaging while also highlighting the pharmacokinetic limitations of full-size antibodies for liver imaging. More recent approaches using antibody fragments, single-domain antibodies, single-chain variable fragments, and macrocyclic peptides have substantially improved imaging contrast at earlier time points and have enabled first-in-human PET studies in patients with HCC and hepatoblastoma. These studies indicate the feasibility of GPC3-targeted radiopharmaceutical therapy but have also demonstrated intrapatient and interpatient heterogeneity of target expression, emphasizing the need for pretherapeutic imaging of GPC3 expression before therapeutic interventions. Thus, GPC3 imaging could contribute not only to the diagnosis and staging of HCC but also to treatment monitoring and the selection of patients for GPC3-targeted therapies. A clinical phase 1 trial with an ²²⁵Ac-labeled macrocyclic peptide ([²²⁵Ac]Ac-RAYZ-8009, RYZ801) using PET with [⁶⁸Ga]Ga-RAYZ-8009 (RYZ811) for patient selection is currently ongoing. Furthermore, an ²²⁵Ac-labeled GPC3 antibody, BAY 3547926, is undergoing phase 1/2 clinical testing.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043075","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":"Implications of the Latest Expanded Label of ¹⁷⁷Lu-PSMA-617 for Nuclear Medicine Practice.","authors":"Steven P Rowe, Ken Herrmann, Michael A Gorin, Kevin Courtney, Scott Tagawa, Oliver Sartor, Michael J Morris, Frankis G Almaguel","doi":"10.2967/jnumed.126.273661","DOIUrl":"https://doi.org/10.2967/jnumed.126.273661","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043032","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}