Pub Date : 2025-11-25DOI: 10.2967/jnumed.124.268339
Konstantinos Chiotis,Yingbing Wang,Renaud La Joie,Gil D Rabinovici
The advent of amyloid-β (Aβ) and tau PET imaging has revolutionized Alzheimer disease (AD) research, enabling in vivo detection of hallmark pathologies and transforming both diagnosis and therapeutic development. These imaging modalities have played a central role in the clinical trials that led to the recent approval of Aβ-targeting therapies, with Aβ PET used for participant selection and treatment monitoring and tau PET increasingly integrated to assess disease staging and prognosis. This continuing-education article reviews the current clinical validation of Aβ and tau PET imaging in AD, outlines the available evidence for the recently approved anti-Aβ therapies, and examines how PET imaging was operationalized in the trials for these novel therapeutic agents. We explore the potential for translating trial-based imaging protocols into clinical practice-particularly how PET quantification beyond binary visual reads can support nuanced decisions regarding patient eligibility, risk stratification, therapeutic monitoring, and duration of treatment. In addition, we discuss the emerging landscape of tau-targeting therapies and the anticipated central role of tau PET in their clinical evaluation. Finally, we identify key knowledge gaps and unmet needs that must be addressed to facilitate broader clinical adoption of PET imaging, including standardization efforts, accessibility and reimbursement, and evidence-based guidelines for interpretation and use.
{"title":"The Role of Amyloid-β and Tau PET in the New Era of Alzheimer Disease Therapies.","authors":"Konstantinos Chiotis,Yingbing Wang,Renaud La Joie,Gil D Rabinovici","doi":"10.2967/jnumed.124.268339","DOIUrl":"https://doi.org/10.2967/jnumed.124.268339","url":null,"abstract":"The advent of amyloid-β (Aβ) and tau PET imaging has revolutionized Alzheimer disease (AD) research, enabling in vivo detection of hallmark pathologies and transforming both diagnosis and therapeutic development. These imaging modalities have played a central role in the clinical trials that led to the recent approval of Aβ-targeting therapies, with Aβ PET used for participant selection and treatment monitoring and tau PET increasingly integrated to assess disease staging and prognosis. This continuing-education article reviews the current clinical validation of Aβ and tau PET imaging in AD, outlines the available evidence for the recently approved anti-Aβ therapies, and examines how PET imaging was operationalized in the trials for these novel therapeutic agents. We explore the potential for translating trial-based imaging protocols into clinical practice-particularly how PET quantification beyond binary visual reads can support nuanced decisions regarding patient eligibility, risk stratification, therapeutic monitoring, and duration of treatment. In addition, we discuss the emerging landscape of tau-targeting therapies and the anticipated central role of tau PET in their clinical evaluation. Finally, we identify key knowledge gaps and unmet needs that must be addressed to facilitate broader clinical adoption of PET imaging, including standardization efforts, accessibility and reimbursement, and evidence-based guidelines for interpretation and use.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-25DOI: 10.2967/jnumed.125.271249
Akram Al-Ibraheem
{"title":"Worldwide Potential of Radiotheranostics and the Challenges Faced by Developing Countries.","authors":"Akram Al-Ibraheem","doi":"10.2967/jnumed.125.271249","DOIUrl":"https://doi.org/10.2967/jnumed.125.271249","url":null,"abstract":"","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-25DOI: 10.2967/jnumed.125.269540
Arman Rahmim,Tyler J Bradshaw,Guido Davidzon,Joyita Dutta,Georges El Fakhri,Munir Ghesani,Nicolas A Karakatsanis,Quanzheng Li,Chi Liu,Emilie Roncali,Babak Saboury,Tahir Yusufaly,Abhinav K Jha
The second Society of Nuclear Medicine and Molecular Imaging (SNMMI) AI Summit, organized by the SNMMI AI Task Force, took place in Bethesda, MD, on February 29-March 1, 2024. Bringing together various community members and stakeholders and following up on a successful 2022 summit, the theme was "AI in Action." Key items discussed included emerging needs and tools for computational nuclear oncology, new frontiers in large language and generative models, defining the value proposition for the use of artificial intelligence in nuclear medicine, open science including efforts for data and model repositories, and issues of reimbursement and funding. The primary efforts, findings, challenges, and next steps are summarized in this article.
{"title":"Nuclear Medicine AI in Action: The Bethesda Report (AI Summit 2024).","authors":"Arman Rahmim,Tyler J Bradshaw,Guido Davidzon,Joyita Dutta,Georges El Fakhri,Munir Ghesani,Nicolas A Karakatsanis,Quanzheng Li,Chi Liu,Emilie Roncali,Babak Saboury,Tahir Yusufaly,Abhinav K Jha","doi":"10.2967/jnumed.125.269540","DOIUrl":"https://doi.org/10.2967/jnumed.125.269540","url":null,"abstract":"The second Society of Nuclear Medicine and Molecular Imaging (SNMMI) AI Summit, organized by the SNMMI AI Task Force, took place in Bethesda, MD, on February 29-March 1, 2024. Bringing together various community members and stakeholders and following up on a successful 2022 summit, the theme was \"AI in Action.\" Key items discussed included emerging needs and tools for computational nuclear oncology, new frontiers in large language and generative models, defining the value proposition for the use of artificial intelligence in nuclear medicine, open science including efforts for data and model repositories, and issues of reimbursement and funding. The primary efforts, findings, challenges, and next steps are summarized in this article.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-20DOI: 10.2967/jnumed.125.270850
Timo Bartel,Kim M Pabst,Christina Barg,Christoph A Berliner,Rainer Hamacher,Sebastian Bauer,Johanna Falkenhorst,Lukas Kessler,Michael Nader,Francesco Barbato,Jens T Siveke,Ken Herrmann,Wolfgang P Fendler
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Although contrast-enhanced CT (ceCT) and 2-[18F]FDG PET/CT remain standard imaging modalities, both exhibit limitations in detecting small peritoneal metastases and tumors with low metabolic activity. 68Ga-labeled fibroblast activation protein inhibitors (FAPIs) have shown promising results in various malignancies; however, comparative data on GISTs are limited. This study aimed to assess the diagnostic performance of [68Ga]Ga-FAPI-46 PET/CT in comparison with 2-[18F]FDG PET/CT and ceCT, including evaluation of interreader reproducibility and clinical impact. Methods: This study retrospectively reviewed 25 patients with histopathologically confirmed GISTs undergoing [68Ga]Ga-FAPI-46 PET/CT as part of a prospective observational study (NCT04571086). All patients (n = 25) underwent additional clinical 2-[18F]FDG PET/CT; ceCT was performed for 23 of 25 patients. Imaging was assessed per patient and per region (primary tumor, lymph nodes, and visceral and bone metastases), and a composite reference standard that included histopathology, follow-up imaging, and clinical data was applied. Interreader agreement, stratified by experience level, was analyzed using Cohen κ (κCohen). Referring physicians completed questionnaires before and after imaging to determine clinical impact. Results: In total, 28 validated regions (n = 20 patients) were included in the diagnostic efficacy analysis. Per region, ceCT and [68Ga]Ga-FAPI-46 PET/CT demonstrated comparable sensitivity (83% vs. 81%), followed by 2-[18F]FDG PET/CT (65%). [68Ga]Ga-FAPI-46 PET/CT demonstrated the highest region-based positive predictive value (100%). The liver tumor-to-background ratio was significantly higher for [68Ga]Ga-FAPI-46 PET/CT than for 2-[18F]FDG PET/CT (median, 7.6 vs. 5.9; P = 0.034), whereas overall tumor uptake showed no significant difference. Changes in clinical management attributable to [68Ga]Ga-FAPI-46 PET/CT were observed for 6 of 24 patients (25%), including 1 major change. Interreader agreement for [68Ga]Ga-FAPI-46 PET/CT varied with reader experience, showing the highest concordance between high- and intermediate-experience readers (κCohen = 0.87 per patient and 0.47-1.00 across regions), whereas comparisons involving less experienced readers yielded lower agreement (κCohen = 0.00-0.60). Conclusion: [68Ga]Ga-FAPI-46 PET/CT demonstrated diagnostic sensitivity comparable to ceCT and superior to 2-[18F]FDG PET/CT for patients with GISTs. High diagnostic performance, especially in hepatic and peritoneal metastases, and relevant clinical impact support a role for [68Ga]Ga-FAPI-46 PET/CT as complementary imaging modality.
{"title":"[68Ga]Ga-FAPI-46 PET/CT of Patients with Gastrointestinal Stromal Tumors in Comparison to 2-[18F]FDG PET/CT and Contrast-Enhanced CT: Results from a Prospective Observational Study.","authors":"Timo Bartel,Kim M Pabst,Christina Barg,Christoph A Berliner,Rainer Hamacher,Sebastian Bauer,Johanna Falkenhorst,Lukas Kessler,Michael Nader,Francesco Barbato,Jens T Siveke,Ken Herrmann,Wolfgang P Fendler","doi":"10.2967/jnumed.125.270850","DOIUrl":"https://doi.org/10.2967/jnumed.125.270850","url":null,"abstract":"Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Although contrast-enhanced CT (ceCT) and 2-[18F]FDG PET/CT remain standard imaging modalities, both exhibit limitations in detecting small peritoneal metastases and tumors with low metabolic activity. 68Ga-labeled fibroblast activation protein inhibitors (FAPIs) have shown promising results in various malignancies; however, comparative data on GISTs are limited. This study aimed to assess the diagnostic performance of [68Ga]Ga-FAPI-46 PET/CT in comparison with 2-[18F]FDG PET/CT and ceCT, including evaluation of interreader reproducibility and clinical impact. Methods: This study retrospectively reviewed 25 patients with histopathologically confirmed GISTs undergoing [68Ga]Ga-FAPI-46 PET/CT as part of a prospective observational study (NCT04571086). All patients (n = 25) underwent additional clinical 2-[18F]FDG PET/CT; ceCT was performed for 23 of 25 patients. Imaging was assessed per patient and per region (primary tumor, lymph nodes, and visceral and bone metastases), and a composite reference standard that included histopathology, follow-up imaging, and clinical data was applied. Interreader agreement, stratified by experience level, was analyzed using Cohen κ (κCohen). Referring physicians completed questionnaires before and after imaging to determine clinical impact. Results: In total, 28 validated regions (n = 20 patients) were included in the diagnostic efficacy analysis. Per region, ceCT and [68Ga]Ga-FAPI-46 PET/CT demonstrated comparable sensitivity (83% vs. 81%), followed by 2-[18F]FDG PET/CT (65%). [68Ga]Ga-FAPI-46 PET/CT demonstrated the highest region-based positive predictive value (100%). The liver tumor-to-background ratio was significantly higher for [68Ga]Ga-FAPI-46 PET/CT than for 2-[18F]FDG PET/CT (median, 7.6 vs. 5.9; P = 0.034), whereas overall tumor uptake showed no significant difference. Changes in clinical management attributable to [68Ga]Ga-FAPI-46 PET/CT were observed for 6 of 24 patients (25%), including 1 major change. Interreader agreement for [68Ga]Ga-FAPI-46 PET/CT varied with reader experience, showing the highest concordance between high- and intermediate-experience readers (κCohen = 0.87 per patient and 0.47-1.00 across regions), whereas comparisons involving less experienced readers yielded lower agreement (κCohen = 0.00-0.60). Conclusion: [68Ga]Ga-FAPI-46 PET/CT demonstrated diagnostic sensitivity comparable to ceCT and superior to 2-[18F]FDG PET/CT for patients with GISTs. High diagnostic performance, especially in hepatic and peritoneal metastases, and relevant clinical impact support a role for [68Ga]Ga-FAPI-46 PET/CT as complementary imaging modality.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-20DOI: 10.2967/jnumed.125.270348
Adam L Kesner,Nikki Batista,Pat Zanzonico,Cathy S Cutler
{"title":"A Cures Act-Forged Pathway to Patient-Tailored Radiopharmaceutical Therapy and Call for Regulatory Transparency.","authors":"Adam L Kesner,Nikki Batista,Pat Zanzonico,Cathy S Cutler","doi":"10.2967/jnumed.125.270348","DOIUrl":"https://doi.org/10.2967/jnumed.125.270348","url":null,"abstract":"","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145558997","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}
Our team previously reported a preclinical study of 2 novel prostate-specific membrane antigen (PSMA)-targeted compounds that incorporate a hypoxia-sensitive nitroimidazole (NI) moiety-6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid-PSMA-093 (AZ-093) and its hypoxia-responsive derivative 6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid-NI-PSMA-093 (AZ-NI-093). This prospective trial aims to evaluate the clinical value of both agents in patients with prostate cancer, specifically exploring the impact of NI on tumor uptake. Methods: Sixty patients were enrolled in this PET/CT imaging study. Thirty patients underwent a head-to-head comparison of [68Ga]Ga-AZ-093 with [68Ga]Ga-PSMA-11 or [68Ga]Ga-PSMA-617, and 30 patients underwent a head-to-head comparison of [68Ga]Ga-AZ-NI-093 with [68Ga]Ga-AZ-093. The number of tumors and SUV for tumors and organs were measured and recorded. SUVmax differences between [68Ga]Ga-AZ-NI-093 and [68Ga]Ga-AZ-093 PET/CT were calculated for further analysis. Immunohistochemical staining for hypoxia-inducible factor 1 was performed on 12 surgical specimens of intraprostatic tumors. Results: All patients tolerated [68Ga]Ga-based PET/CT scans without adverse effects. The initial biodistribution of [68Ga]Ga-AZ-093 and [68Ga]Ga-AZ-NI-093 in humans, as assessed by PET/CT, was comparable to that of other PSMA-targeted radiopharmaceuticals, with respective effective absorbed doses of 0.0128 ± 0.00594 and 0.0160 ± 0.000869 mSv/MBq. [68Ga]Ga-AZ-093 exhibited higher tumor uptake 60 min after injection compared with [68Ga]Ga-PSMA-11 (SUVmax, 22.2 ± 10.8 vs. 20.4 ± 14.8; P = 0.025) and [68Ga]Ga-PSMA-617 (SUVmax, 20.1 ± 12.7 vs. 10.8 ± 8.7; P < 0.001), while maintaining comparable tumor detection rates. [68Ga]Ga-AZ-NI-093 showed further improved tumor uptake relative to [68Ga]Ga-AZ-093 at 60 min (SUVmax, 17.8 ± 14.0 vs. 16.3 ± 11.5; P = 0.009) and 150 min (31.3 ± 18.5 vs. 28.7 ± 17.5; P = 0.003), especially in large-volume, high-grade intraprostatic tumor and metastatic sites. The expression of hypoxia-inducible factor 1 in tumors, as an indicator of hypoxia, demonstrated a significant association with International Society of Urological Pathology grade (r = 0.519; P = 0.038) and difference in SUVmax (r = 0.629; P = 0.023). Conclusion: Both [68Ga]Ga-AZ-093 and [68Ga]Ga-AZ-NI-093 represent promising PSMA-targeted radiopharmaceuticals. [68Ga]Ga-AZ-NI-093 demonstrated potential in targeting hypoxic tumor tissues. Future studies with larger sample sizes are needed to further explore the clinical value of these radiopharmaceuticals.
我们的团队之前报道了两种新型前列腺特异性膜抗原（PSMA）靶向化合物的临床前研究，这些化合物包含缺氧敏感的硝基咪唑（NI）基团-6-氨基-6-甲基过氢-1,4-二氮卓四乙酸-PSMA-093 （AZ-093）及其缺氧反应衍生物-6-氨基-6-甲基过氢-1,4-二氮卓四乙酸-NI-PSMA-093 （AZ-NI-093）。这项前瞻性试验旨在评估这两种药物在前列腺癌患者中的临床价值，特别是探讨NI对肿瘤摄取的影响。方法：对60例患者进行PET/CT成像研究。30例患者进行了[68Ga]Ga-AZ-093与[68Ga]Ga-PSMA-11或[68Ga]Ga-PSMA-617的头部比较，30例患者进行了[68Ga]Ga-AZ-NI-093与[68Ga]Ga-AZ-093的头部比较。测量并记录肿瘤数量及肿瘤与器官的SUV。计算[68Ga]Ga-AZ-NI-093与[68Ga]Ga-AZ-093 PET/CT的SUVmax差异，进一步分析。对12例前列腺内肿瘤手术标本进行缺氧诱导因子1免疫组化染色。结果：所有患者耐受基于[68Ga] ga的PET/CT扫描，无不良反应。通过PET/CT评估，[68Ga]Ga-AZ-093和[68Ga]Ga-AZ-NI-093在人体中的初始生物分布与其他psma靶向放射性药物相当，有效吸收剂量分别为0.0128±0.00594和0.0160±0.000869 mSv/MBq。与[68Ga]Ga-PSMA-11 （SUVmax, 22.2±10.8比20.4±14.8,P = 0.025）和[68Ga]Ga-PSMA-617 （SUVmax, 20.1±12.7比10.8±8.7,P < 0.001）相比，[68Ga]Ga-AZ-093注射后60 min的肿瘤摄取率更高，但肿瘤检出率保持相当。与[68Ga]Ga-AZ-NI-093相比，[68Ga]Ga-AZ-093在60分钟（SUVmax, 17.8±14.0 vs. 16.3±11.5,P = 0.009）和150分钟（31.3±18.5 vs. 28.7±17.5,P = 0.003）时的肿瘤摄取进一步改善，特别是在大体积、高级别前列腺内肿瘤和转移部位。低氧诱导因子1在肿瘤中的表达与国际泌尿病理学会分级（r = 0.519; P = 0.038）及SUVmax的差异（r = 0.629; P = 0.023）有显著相关性。结论：[68Ga]Ga-AZ-093和[68Ga]Ga-AZ-NI-093都是有前景的psma靶向放射性药物。[68Ga]Ga-AZ-NI-093具有靶向缺氧肿瘤组织的潜力。未来需要更大样本量的研究来进一步探索这些放射性药物的临床价值。
{"title":"First-in-Human PET Imaging of Prostate Cancer Using [68Ga]Ga-AZ-093 and Its Nitroimidazole-Conjugated Derivative [68Ga]Ga-AZ-NI-093.","authors":"Guochang Wang,Yuxin Lai,Dongning Chen,Wenbin Jin,Yang Luo,Yumeng Peng,Hank F Kung,Lin Zhu,Jie Zang,Ning Xu,Weibing Miao","doi":"10.2967/jnumed.125.270703","DOIUrl":"https://doi.org/10.2967/jnumed.125.270703","url":null,"abstract":"Our team previously reported a preclinical study of 2 novel prostate-specific membrane antigen (PSMA)-targeted compounds that incorporate a hypoxia-sensitive nitroimidazole (NI) moiety-6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid-PSMA-093 (AZ-093) and its hypoxia-responsive derivative 6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid-NI-PSMA-093 (AZ-NI-093). This prospective trial aims to evaluate the clinical value of both agents in patients with prostate cancer, specifically exploring the impact of NI on tumor uptake. Methods: Sixty patients were enrolled in this PET/CT imaging study. Thirty patients underwent a head-to-head comparison of [68Ga]Ga-AZ-093 with [68Ga]Ga-PSMA-11 or [68Ga]Ga-PSMA-617, and 30 patients underwent a head-to-head comparison of [68Ga]Ga-AZ-NI-093 with [68Ga]Ga-AZ-093. The number of tumors and SUV for tumors and organs were measured and recorded. SUVmax differences between [68Ga]Ga-AZ-NI-093 and [68Ga]Ga-AZ-093 PET/CT were calculated for further analysis. Immunohistochemical staining for hypoxia-inducible factor 1 was performed on 12 surgical specimens of intraprostatic tumors. Results: All patients tolerated [68Ga]Ga-based PET/CT scans without adverse effects. The initial biodistribution of [68Ga]Ga-AZ-093 and [68Ga]Ga-AZ-NI-093 in humans, as assessed by PET/CT, was comparable to that of other PSMA-targeted radiopharmaceuticals, with respective effective absorbed doses of 0.0128 ± 0.00594 and 0.0160 ± 0.000869 mSv/MBq. [68Ga]Ga-AZ-093 exhibited higher tumor uptake 60 min after injection compared with [68Ga]Ga-PSMA-11 (SUVmax, 22.2 ± 10.8 vs. 20.4 ± 14.8; P = 0.025) and [68Ga]Ga-PSMA-617 (SUVmax, 20.1 ± 12.7 vs. 10.8 ± 8.7; P < 0.001), while maintaining comparable tumor detection rates. [68Ga]Ga-AZ-NI-093 showed further improved tumor uptake relative to [68Ga]Ga-AZ-093 at 60 min (SUVmax, 17.8 ± 14.0 vs. 16.3 ± 11.5; P = 0.009) and 150 min (31.3 ± 18.5 vs. 28.7 ± 17.5; P = 0.003), especially in large-volume, high-grade intraprostatic tumor and metastatic sites. The expression of hypoxia-inducible factor 1 in tumors, as an indicator of hypoxia, demonstrated a significant association with International Society of Urological Pathology grade (r = 0.519; P = 0.038) and difference in SUVmax (r = 0.629; P = 0.023). Conclusion: Both [68Ga]Ga-AZ-093 and [68Ga]Ga-AZ-NI-093 represent promising PSMA-targeted radiopharmaceuticals. [68Ga]Ga-AZ-NI-093 demonstrated potential in targeting hypoxic tumor tissues. Future studies with larger sample sizes are needed to further explore the clinical value of these radiopharmaceuticals.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-20DOI: 10.2967/jnumed.125.270508
Serge K Lyashchenko,Tullio V Esposito,Tuan Tran,David Bauer,Kali Jones,Hijin Park,Lukas M Carter,Naga Vara Kishore Pillarsetty,Jason S Lewis
Currently, the most applied 89Zr-immuno-PET platform is the [89Zr]Zr-deferoxamine (DFO)-monoclonal antibody (mAb) constructs, where the investigational agent is obtained through combining [89Zr]Zr-oxalate with mAbs conjugated to the bifunctional chelator p-SCN-Bn-DFO. This approach struggles with several limitations, including the inability of DFO to incorporate lanthanide-based radiometals such as 177Lu or 161Tb and the instability of the [89Zr]Zr-DFO complex in ascorbate-containing formulations. Conversely, whereas pentetic acid (DTPA)-based bifunctional chelators have been extensively applied to generate clinical β-therapeutic mAb constructs, the previous efforts to create stable [89Zr]Zr-DTPA-mAb complexes using [89Zr]Zr-oxalate have been unsuccessful. However, [89Zr]ZrCl4, which exists as [Zr4(OH)8(OH2)16]8+ in aqueous solutions, is chemically more accessible than its commercially available oxalate form, enabling the direct labeling of p-SCN-Bn-CHX-A″-DTPA. The methodology described here allows for the generation of [89Zr]Zr-DTPA-mAb and [177Lu]Lu/[161Tb]Tb-DTPA-mAb radiotheranostic pairs, where the targeting vector in the diagnostic and the therapeutic analogs is identical. Methods: Pertuzumab was selected for proof-of-concept studies and was conjugated to p-SCN-Bn-CHX-A″-DTPA. Radiolabeling of DTPA-pertuzumab with [89Zr]ZrCl4 involved a 10-min incubation in acetate buffer (pH 4.5), followed by PD-10 desalting gel column purification. The in-formulation radiochemical purity and pooled human serum stability were assessed using size-exclusion high-performance liquid chromatography, and radioimmunoreactivity was evaluated using the stationary antigen magnetic bead-based method. Biodistribution of [89Zr]Zr-DTPA-pertuzumab was assessed in BT-474 tumor mouse models and compared with biodistribution of [89Zr]Zr-DFO-pertuzumab and [161Tb]Tb-DTPA-pertuzumab. Results: Conjugated batches consistently produced DTPA-pertuzumab with acceptable chelate-to-mAb ratios and chemical purity. DTPA-pertuzumab was radiolabeled with up to 3.4 GBq (92 mCi) of 89Zr. In formulation, DTPA-pertuzumab exhibited greater chemical stability, and the radioaggregate formation was lower in [89Zr]Zr-DTPA-pertuzumab than in [89Zr]Zr-DFO-pertuzumab. [89Zr]Zr-DTPA-pertuzumab was also stable in ascorbate-containing formulations. In human serum, the drop in radiomonomer content for [89Zr]Zr-DTPA-pertuzumab was smaller than for [89Zr]Zr-DFO-pertuzumab. Compared with [89Zr]Zr-DFO-pertuzumab, [89Zr]Zr-DTPA-pertuzumab biodistribution exhibited lower liver and higher blood and tumor uptake and was more consistent with the biodistribution of [161Tb]Tb-DTPA-pertuzumab. Conclusion: The ability to radiolabel CHX-A″-DTPA-mAbs with 89Zr has been demonstrated, allowing for the generation of 89Zr/177Lu/161Tb-based true radiotheranostic pairs. On the basis of our biodistribution data, [89Zr]Zr-DTPA-mAbs may be better suited as a companion diagnostic to radiotherapeutic DTPA-mAb analogs than is [
{"title":"Radiolabeling of CHX-A″-DTPA-Antibody Conjugates with [89Zr]ZrCl4.","authors":"Serge K Lyashchenko,Tullio V Esposito,Tuan Tran,David Bauer,Kali Jones,Hijin Park,Lukas M Carter,Naga Vara Kishore Pillarsetty,Jason S Lewis","doi":"10.2967/jnumed.125.270508","DOIUrl":"https://doi.org/10.2967/jnumed.125.270508","url":null,"abstract":"Currently, the most applied 89Zr-immuno-PET platform is the [89Zr]Zr-deferoxamine (DFO)-monoclonal antibody (mAb) constructs, where the investigational agent is obtained through combining [89Zr]Zr-oxalate with mAbs conjugated to the bifunctional chelator p-SCN-Bn-DFO. This approach struggles with several limitations, including the inability of DFO to incorporate lanthanide-based radiometals such as 177Lu or 161Tb and the instability of the [89Zr]Zr-DFO complex in ascorbate-containing formulations. Conversely, whereas pentetic acid (DTPA)-based bifunctional chelators have been extensively applied to generate clinical β-therapeutic mAb constructs, the previous efforts to create stable [89Zr]Zr-DTPA-mAb complexes using [89Zr]Zr-oxalate have been unsuccessful. However, [89Zr]ZrCl4, which exists as [Zr4(OH)8(OH2)16]8+ in aqueous solutions, is chemically more accessible than its commercially available oxalate form, enabling the direct labeling of p-SCN-Bn-CHX-A″-DTPA. The methodology described here allows for the generation of [89Zr]Zr-DTPA-mAb and [177Lu]Lu/[161Tb]Tb-DTPA-mAb radiotheranostic pairs, where the targeting vector in the diagnostic and the therapeutic analogs is identical. Methods: Pertuzumab was selected for proof-of-concept studies and was conjugated to p-SCN-Bn-CHX-A″-DTPA. Radiolabeling of DTPA-pertuzumab with [89Zr]ZrCl4 involved a 10-min incubation in acetate buffer (pH 4.5), followed by PD-10 desalting gel column purification. The in-formulation radiochemical purity and pooled human serum stability were assessed using size-exclusion high-performance liquid chromatography, and radioimmunoreactivity was evaluated using the stationary antigen magnetic bead-based method. Biodistribution of [89Zr]Zr-DTPA-pertuzumab was assessed in BT-474 tumor mouse models and compared with biodistribution of [89Zr]Zr-DFO-pertuzumab and [161Tb]Tb-DTPA-pertuzumab. Results: Conjugated batches consistently produced DTPA-pertuzumab with acceptable chelate-to-mAb ratios and chemical purity. DTPA-pertuzumab was radiolabeled with up to 3.4 GBq (92 mCi) of 89Zr. In formulation, DTPA-pertuzumab exhibited greater chemical stability, and the radioaggregate formation was lower in [89Zr]Zr-DTPA-pertuzumab than in [89Zr]Zr-DFO-pertuzumab. [89Zr]Zr-DTPA-pertuzumab was also stable in ascorbate-containing formulations. In human serum, the drop in radiomonomer content for [89Zr]Zr-DTPA-pertuzumab was smaller than for [89Zr]Zr-DFO-pertuzumab. Compared with [89Zr]Zr-DFO-pertuzumab, [89Zr]Zr-DTPA-pertuzumab biodistribution exhibited lower liver and higher blood and tumor uptake and was more consistent with the biodistribution of [161Tb]Tb-DTPA-pertuzumab. Conclusion: The ability to radiolabel CHX-A″-DTPA-mAbs with 89Zr has been demonstrated, allowing for the generation of 89Zr/177Lu/161Tb-based true radiotheranostic pairs. On the basis of our biodistribution data, [89Zr]Zr-DTPA-mAbs may be better suited as a companion diagnostic to radiotherapeutic DTPA-mAb analogs than is [","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"106 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559012","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}
The primary aim of this study was to compare the diagnostic accuracy of [68Ga]Ga-PSMA-11 PET, [68Ga]Ga-RM2 PET, and multiparametric MRI (mpMRI) for the detection of primary prostate cancer (PCa) using histopathology as the reference. The secondary aims of the study were to assess the agreement among imaging modalities and identify noninvasive biomarkers for the diagnosis and risk stratification of patients. Methods: Forty-two patients with biopsy-confirmed, high-risk PCa were enrolled in this single-center, prospective, phase 2 clinical trial between September 2020 and May 2023 at San Raffaele hospital. All patients underwent [68Ga]Ga-PSMA-11 PET/MRI with mpMRI, and 36 had additional imaging with [68Ga]Ga-RM2 PET/MRI. All patients were included in the patient-level T staging analysis. Twenty-five patients were treated with radical prostatectomy with extended lymphadenectomy and considered for N staging analysis. Sixteen patients underwent all imaging and surgical procedures needed for coregistration between imaging and histology and were included in the lesion-based analysis for T staging. Two expert nuclear medicine physicians reviewed [68Ga]Ga-PSMA-11 and [68Ga]Ga-RM2 PET images with knowledge of the patients' available clinical and imaging information. mpMRI was interpreted as the standard of care by 2 expert radiologists using Prostate Imaging Reporting and Data System, version 2, criteria. Peripheral whole-blood samples were collected at the time of patient's enrollment to assess their association with lymph node involvement on histology. Results: In the patient-based analysis, [68Ga]Ga-PSMA-11 PET and mpMRI identified at least 1 intraprostatic lesion in all patients, whereas [68Ga]Ga-RM2 PET results were negative in 3 of 36 patients. The lesion-level analysis performed in 16 patients showed that, in this cohort, the dominant intraprostatic lesion was always detected by [68Ga]Ga-RM2 PET, whereas both [68Ga]Ga-PSMA-11 PET and mpMRI missed it, reporting a false-positive finding elsewhere. For N staging analysis, [68Ga]Ga-PSMA-11 PET had the highest sensitivity among the investigated imaging modalities (sensitivity, 0.375). Blood analysis showed that a higher fraction of polymorphonuclear-myeloid-derived suppressor cells (MDSCs) over monocytic MDSCs was significantly associated patients with lymph node involvement on histology (P = 0.0285). Conclusion: All imaging modalities showed high sensitivity for the preoperative detection of primary PCa, but only [68Ga]Ga-RM2 PET correctly identified the dominant lesion in all patients who underwent lesion-based subanalysis. The identification of lymph node involvement remains challenging, with [68Ga]Ga-PSMA-11 PET reaching a sensitivity of only 0.375. In this regard, the polymorphonuclear MDSC-to-monocytic MDSC ratio may represent a valuable biologic marker of lymph node involvement in patients with high-risk PCa and warrants further investigation.
{"title":"Diagnostic Accuracy of Fully Hybrid PET/MRI with [68Ga]Ga-PSMA-11 and [68Ga]Ga-RM2 in Detecting Primary Prostate Cancer: A Phase 2 Trial with Histology as Gold Standard.","authors":"Samuele Ghezzo,Paola Mapelli,Laura Lucia Cogrossi,Ana Maria Samanes Gajate,Giorgio Brembilla,Vito Cucchiara,Benedetta Mattorre,Tommaso Russo,Carolina Bezzi,Ilaria Neri,Sebastiano Vadalà,Andrea Alimonti,Massimo Freschi,Alberto Briganti,Francesco De Cobelli,Arturo Chiti,Matteo Bellone,Paola Scifo,Maria Picchio","doi":"10.2967/jnumed.125.269782","DOIUrl":"https://doi.org/10.2967/jnumed.125.269782","url":null,"abstract":"The primary aim of this study was to compare the diagnostic accuracy of [68Ga]Ga-PSMA-11 PET, [68Ga]Ga-RM2 PET, and multiparametric MRI (mpMRI) for the detection of primary prostate cancer (PCa) using histopathology as the reference. The secondary aims of the study were to assess the agreement among imaging modalities and identify noninvasive biomarkers for the diagnosis and risk stratification of patients. Methods: Forty-two patients with biopsy-confirmed, high-risk PCa were enrolled in this single-center, prospective, phase 2 clinical trial between September 2020 and May 2023 at San Raffaele hospital. All patients underwent [68Ga]Ga-PSMA-11 PET/MRI with mpMRI, and 36 had additional imaging with [68Ga]Ga-RM2 PET/MRI. All patients were included in the patient-level T staging analysis. Twenty-five patients were treated with radical prostatectomy with extended lymphadenectomy and considered for N staging analysis. Sixteen patients underwent all imaging and surgical procedures needed for coregistration between imaging and histology and were included in the lesion-based analysis for T staging. Two expert nuclear medicine physicians reviewed [68Ga]Ga-PSMA-11 and [68Ga]Ga-RM2 PET images with knowledge of the patients' available clinical and imaging information. mpMRI was interpreted as the standard of care by 2 expert radiologists using Prostate Imaging Reporting and Data System, version 2, criteria. Peripheral whole-blood samples were collected at the time of patient's enrollment to assess their association with lymph node involvement on histology. Results: In the patient-based analysis, [68Ga]Ga-PSMA-11 PET and mpMRI identified at least 1 intraprostatic lesion in all patients, whereas [68Ga]Ga-RM2 PET results were negative in 3 of 36 patients. The lesion-level analysis performed in 16 patients showed that, in this cohort, the dominant intraprostatic lesion was always detected by [68Ga]Ga-RM2 PET, whereas both [68Ga]Ga-PSMA-11 PET and mpMRI missed it, reporting a false-positive finding elsewhere. For N staging analysis, [68Ga]Ga-PSMA-11 PET had the highest sensitivity among the investigated imaging modalities (sensitivity, 0.375). Blood analysis showed that a higher fraction of polymorphonuclear-myeloid-derived suppressor cells (MDSCs) over monocytic MDSCs was significantly associated patients with lymph node involvement on histology (P = 0.0285). Conclusion: All imaging modalities showed high sensitivity for the preoperative detection of primary PCa, but only [68Ga]Ga-RM2 PET correctly identified the dominant lesion in all patients who underwent lesion-based subanalysis. The identification of lymph node involvement remains challenging, with [68Ga]Ga-PSMA-11 PET reaching a sensitivity of only 0.375. In this regard, the polymorphonuclear MDSC-to-monocytic MDSC ratio may represent a valuable biologic marker of lymph node involvement in patients with high-risk PCa and warrants further investigation.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-20DOI: 10.2967/jnumed.125.270593
Merle C Hoenig,Verena Dzialas,Elena Doering,Gérard N Bischof,Thilo van Eimeren,Alexander Drzezga,
There are 14 modifiable factors that are associated with a significantly lower risk of dementia. We tested the interactive effect of modifiable factors, genetic determinants, and initial pathologic burden on the spatial progression and local amplification of tau pathology. Methods: In total, 162 amyloid-positive individuals were included, for whom longitudinal [18F]AV-1451 PET scans, baseline information on global amyloid burden, ApoE4 status, body mass index (BMI), hypertension, education, neuropsychiatric symptom severity, and demographic information were available in the Alzheimer Disease Neuroimaging Initiative. All [18F]AV-1451 scans were intensity-standardized (reference: inferior cerebellum), z-transformed (control sample: 147 amyloid-negative subjects), thresholded (z score, >1.96), and converted to volume maps. Longitudinal tau changes were then assessed in terms of tau spatial extent (i.e., newly affected volume at follow-up) and tau level rise (i.e., tau increase in previously affected volume). These 2 measures were entered as dependent variables in linear mixed-effects models, including baseline modifiable risk factors (BMI, education, hypertension, neuropsychiatric symptom severity), global amyloid, tau volume or tau burden, ApoE4 status, clinical stage, sex, and age as predictors. Next, we tested the interactive effects between baseline amyloid or tau burden with the 4 modifiable factors on tau extent or tau level rise, respectively. Results: Greater tau extent was linked to higher BMI (β = 0.002; 95% CI, 0.0003-0.003), ApoE4 status (β = 0.024; 95% CI, 0.001-0.046), and baseline tau volume (β = 0.207; 95% CI, 0.107-0.308) across groups. In terms of tau level rise, we observed that absence of hypertension (β = 0.295; 95% CI, -0.477 to -0.114), dementia group (β = 0.305; 95% CI, 0.088-0.522), and BMI (β = 0.011; 95% CI, 0.00004-0.022) were linked to increased tau burden. A load-dependent effect of baseline amyloid and tau volume/burden was found for both tau extent (β = -0.005; 95% CI, -0.008 to -0.002) and tau level rise (β = -0.003; 95% CI, -0.005 to -0.001). Higher amyloid and BMI (β = 0.001; 95% CI, 0.0004-0.001) and lower education and higher tau burden (β = -0.035; 95% CI, -0.064 to -0.006) were linked to greater tau level rise. Conclusion: Education, BMI, and hypertension differentially influence tau's spatial extent and increase by its interaction with initial pathologic burden. Timely modification of these factors may overall slow tau progression.
{"title":"Modifiable Factors Associated with the Longitudinal Increase and Spatial Extent of Tau Pathology in Alzheimer Disease.","authors":"Merle C Hoenig,Verena Dzialas,Elena Doering,Gérard N Bischof,Thilo van Eimeren,Alexander Drzezga, ","doi":"10.2967/jnumed.125.270593","DOIUrl":"https://doi.org/10.2967/jnumed.125.270593","url":null,"abstract":"There are 14 modifiable factors that are associated with a significantly lower risk of dementia. We tested the interactive effect of modifiable factors, genetic determinants, and initial pathologic burden on the spatial progression and local amplification of tau pathology. Methods: In total, 162 amyloid-positive individuals were included, for whom longitudinal [18F]AV-1451 PET scans, baseline information on global amyloid burden, ApoE4 status, body mass index (BMI), hypertension, education, neuropsychiatric symptom severity, and demographic information were available in the Alzheimer Disease Neuroimaging Initiative. All [18F]AV-1451 scans were intensity-standardized (reference: inferior cerebellum), z-transformed (control sample: 147 amyloid-negative subjects), thresholded (z score, >1.96), and converted to volume maps. Longitudinal tau changes were then assessed in terms of tau spatial extent (i.e., newly affected volume at follow-up) and tau level rise (i.e., tau increase in previously affected volume). These 2 measures were entered as dependent variables in linear mixed-effects models, including baseline modifiable risk factors (BMI, education, hypertension, neuropsychiatric symptom severity), global amyloid, tau volume or tau burden, ApoE4 status, clinical stage, sex, and age as predictors. Next, we tested the interactive effects between baseline amyloid or tau burden with the 4 modifiable factors on tau extent or tau level rise, respectively. Results: Greater tau extent was linked to higher BMI (β = 0.002; 95% CI, 0.0003-0.003), ApoE4 status (β = 0.024; 95% CI, 0.001-0.046), and baseline tau volume (β = 0.207; 95% CI, 0.107-0.308) across groups. In terms of tau level rise, we observed that absence of hypertension (β = 0.295; 95% CI, -0.477 to -0.114), dementia group (β = 0.305; 95% CI, 0.088-0.522), and BMI (β = 0.011; 95% CI, 0.00004-0.022) were linked to increased tau burden. A load-dependent effect of baseline amyloid and tau volume/burden was found for both tau extent (β = -0.005; 95% CI, -0.008 to -0.002) and tau level rise (β = -0.003; 95% CI, -0.005 to -0.001). Higher amyloid and BMI (β = 0.001; 95% CI, 0.0004-0.001) and lower education and higher tau burden (β = -0.035; 95% CI, -0.064 to -0.006) were linked to greater tau level rise. Conclusion: Education, BMI, and hypertension differentially influence tau's spatial extent and increase by its interaction with initial pathologic burden. Timely modification of these factors may overall slow tau progression.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"149 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145558996","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：