Pub Date : 2026-01-01Epub Date: 2025-12-18DOI: 10.1053/j.semnuclmed.2025.11.025
Hossein Jadvar , Amir Iravani
Metastatic prostate cancer heterogeneity is a multifactorial spatiotemporally dynamic process that leads to disease progression, emergence of treatment resistance and eventual treatment failure. Understanding of the root causes of tumor heterogeneity is the key to develop strategies for more effective therapies. The intra-patient (inter-tumor), and inter-patient heterogeneity demands combinatorial treatment strategies anchored to patient-specific disease biology that can successfully tackle the complexity of the disease in the hopes of overcoming the biological barriers to cancer control. The aim of this article is to briefly review the elements of metastatic prostate cancer heterogeneity and propose approaches to tackle the ensuing therapeutic challenges to achieve durable clinical efficacy in the context of radiopharmaceutical therapy.
{"title":"Therapy strategies to defeat prostate cancer heterogeneity","authors":"Hossein Jadvar , Amir Iravani","doi":"10.1053/j.semnuclmed.2025.11.025","DOIUrl":"10.1053/j.semnuclmed.2025.11.025","url":null,"abstract":"<div><div>Metastatic prostate cancer heterogeneity is a multifactorial spatiotemporally dynamic process that leads to disease progression, emergence of treatment resistance and eventual treatment failure. Understanding of the root causes of tumor heterogeneity is the key to develop strategies for more effective therapies. The intra-patient (inter-tumor), and inter-patient heterogeneity demands combinatorial treatment strategies anchored to patient-specific disease biology that can successfully tackle the complexity of the disease in the hopes of overcoming the biological barriers to cancer control. The aim of this article is to briefly review the elements of metastatic prostate cancer heterogeneity and propose approaches to tackle the ensuing therapeutic challenges to achieve durable clinical efficacy in the context of radiopharmaceutical therapy.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"56 1","pages":"Pages 18-21"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2026-01-09DOI: 10.1053/j.semnuclmed.2025.11.019
Mariza Vorster , Mike Sathekge
Breast cancer remains one of the most heterogeneous malignancies, with marked variability in biology, therapeutic sensitivity, and clinical outcomes. As treatment strategies evolve toward individualized approaches, early and accurate assessment of response has become critical for optimizing outcomes and minimizing toxicity. Recent Findings: ¹⁸F-FDG PET/CT provides a biologically grounded, non-invasive measure of tumour metabolism, heterogeneity, and early treatment adaptation. Baseline metrics such as SUVmax, metabolic tumour volume (MTV), and total lesion glycolysis (TLG)—reflect proliferative drive and aggressiveness, while early changes (ΔSUV, ΔMTV/TLG after 1–2 cycles) predict pathological complete response (pCR) with high negative predictive value. PET-derived nomograms integrating clinical, molecular, and metabolic data outperform clinicopathologic models alone. Radiomic and artificial-intelligence (AI) analyses further refine prediction by quantifying spatial heterogeneity and enabling subtype-specific modelling. Joint EANM/SNMMI guidelines and NCCN recommendations increasingly endorse ¹⁸F-FDG PET/CT for staging and response monitoring in high-risk or locally advanced disease. ¹⁸F-FDG PET/CT has transitioned from staging to precision-response prediction, particularly in HER2-positive and triple-negative breast cancer. Integration into AI driven nomograms supports adaptive, patient-tailored decisions that minimize toxicity and cost while maximizing benefit. Prospective multicentre validation aligned with EANM/SNMMI/NCCN guidance will consolidate PET’s role in adaptive oncology.
{"title":"18F-FDG PET/CT for prediction of response in breast cancer","authors":"Mariza Vorster , Mike Sathekge","doi":"10.1053/j.semnuclmed.2025.11.019","DOIUrl":"10.1053/j.semnuclmed.2025.11.019","url":null,"abstract":"<div><div>Breast cancer remains one of the most heterogeneous malignancies, with marked variability in biology, therapeutic sensitivity, and clinical outcomes. As treatment strategies evolve toward individualized approaches, early and accurate assessment of response has become critical for optimizing outcomes and minimizing toxicity. Recent Findings: ¹⁸F-FDG PET/CT provides a biologically grounded, non-invasive measure of tumour metabolism, heterogeneity, and early treatment adaptation. Baseline metrics such as SUVmax, metabolic tumour volume (MTV), and total lesion glycolysis (TLG)—reflect proliferative drive and aggressiveness, while early changes (ΔSUV, ΔMTV/TLG after 1–2 cycles) predict pathological complete response (pCR) with high negative predictive value. PET-derived nomograms integrating clinical, molecular, and metabolic data outperform clinicopathologic models alone. Radiomic and artificial-intelligence (AI) analyses further refine prediction by quantifying spatial heterogeneity and enabling subtype-specific modelling. Joint EANM/SNMMI guidelines and NCCN recommendations increasingly endorse ¹⁸F-FDG PET/CT for staging and response monitoring in high-risk or locally advanced disease. ¹⁸F-FDG PET/CT has transitioned from staging to precision-response prediction, particularly in HER2-positive and triple-negative breast cancer. Integration into AI driven nomograms supports adaptive, patient-tailored decisions that minimize toxicity and cost while maximizing benefit. Prospective multicentre validation aligned with EANM/SNMMI/NCCN guidance will consolidate PET’s role in adaptive oncology.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"56 1","pages":"Pages 86-96"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145945884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Accurate response assessment in well-differentiated grade 1/2 neuroendocrine tumors (NETs) remains a major clinical challenge. Conventional size-based radiographic criteria such as Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 often fail to capture the slow, indolent nature of NETs. In these tumors, meaningful survival benefits, particularly after peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTATATE, occur without significant tumor shrinkage, while treatment-related necrotic or inflammatory changes can mimic progression. Several modified anatomical criteria, including Choi and mRECIST, have attempted to address these limitations, but results have been inconsistent and largely retrospective. Somatostatin receptor (SSTR)-PET/CT with [68Ga]Ga-labeled analogues offers the opportunity to quantify biological response at the molecular level, reflecting alterations in receptor density and viable tumor burden. The Response Evaluation Criteria in Neuroendocrine Tumors (RECIN), developed from a post-hoc analysis of the phase II LuCAP trial, integrates semi-quantitative SSTR-PET parameters with conventional CT metrics. Using the summed SULpeak of up to five of the hottest lesions (up to two per organ), RECIN defines molecular partial response as a ≥25% reduction in summed SULpeak, while maintaining RECIST safeguards for progression. Applied to the prospective LuCAP trial dataset, RECIN identified additional responders, detected response earlier, and predicted progression-free survival more accurately than RECIST. By harmonizing biological and morphological information, RECIN provides a practical and reproducible framework tailored to the indolent, receptor-driven biology of NETs. Prospective multicenter validation, and correlation with longer term outcomes are needed to establish RECIN as standardized response criteria for PRRT as well as other treatment modalities for well-differentiated NETs.
{"title":"Response Evaluation Criteria in Grade 1/2 Neuroendocrine Tumors (RECIN)","authors":"Piyush Aggarwal , Swayamjeet Satapathy , Kunal R. Chandekar , Ashwani Sood","doi":"10.1053/j.semnuclmed.2025.11.009","DOIUrl":"10.1053/j.semnuclmed.2025.11.009","url":null,"abstract":"<div><div>Accurate response assessment in well-differentiated grade 1/2 neuroendocrine tumors (NETs) remains a major clinical challenge. Conventional size-based radiographic criteria such as Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 often fail to capture the slow, indolent nature of NETs. In these tumors, meaningful survival benefits, particularly after peptide receptor radionuclide therapy (PRRT) with [<sup>177</sup>Lu]Lu-DOTATATE, occur without significant tumor shrinkage, while treatment-related necrotic or inflammatory changes can mimic progression. Several modified anatomical criteria, including Choi and mRECIST, have attempted to address these limitations, but results have been inconsistent and largely retrospective. Somatostatin receptor (SSTR)-PET/CT with [<sup>68</sup>Ga]Ga-labeled analogues offers the opportunity to quantify biological response at the molecular level, reflecting alterations in receptor density and viable tumor burden. The Response Evaluation Criteria in Neuroendocrine Tumors (RECIN), developed from a post-hoc analysis of the phase II LuCAP trial, integrates semi-quantitative SSTR-PET parameters with conventional CT metrics. Using the summed SULpeak of up to five of the hottest lesions (up to two per organ), RECIN defines molecular partial response as a ≥25% reduction in summed SULpeak, while maintaining RECIST safeguards for progression. Applied to the prospective LuCAP trial dataset, RECIN identified additional responders, detected response earlier, and predicted progression-free survival more accurately than RECIST. By harmonizing biological and morphological information, RECIN provides a practical and reproducible framework tailored to the indolent, receptor-driven biology of NETs. Prospective multicenter validation, and correlation with longer term outcomes are needed to establish RECIN as standardized response criteria for PRRT as well as other treatment modalities for well-differentiated NETs.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"56 1","pages":"Pages 22-30"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-12-26DOI: 10.1053/j.semnuclmed.2025.11.022
Sophie C. Siegmund , Emil Novruzov , Eduards Mamlins , Yuriko Mori , Sven Otto , Martin Canis , Tadashi Watabe , Richard P. Baum , Rudolf A. Werner , Frederik L. Giesel
<div><div>FAP-ligands as novel cancer radiopharmaceuticals in nuclear medicine have been recently translated successfully into the clinical space. Particularly small molecules (i.e. FAPI-46, FAPI-74) and peptides (i.e. FAP-2286, DOTAGA.SA.FAPi) seem to be some of the most promising molecular probes for imaging and therapy. Back in 2019, there have been slight reservations about adopting this new imaging probe, after the decades of the solidly established role of FDG PET/CT in oncological imaging. At that time, it was expected that these novel ligands might challenge Onco-PET as new cornerstones in the individualized tumor staging and even beyond. However, FAP-targeted imaging is today not intended to replace FDG PET/CT, but rather to complement cancer imaging and therapy, where cancer subtypes exhibit low glucose metabolism which often leads to moderate or very insufficient FDG uptake. Recently, numerous FAP-imaging studies -ranging from single-case reports to larger patient cohorts and even prospective trials have reinforced the empirical understanding of FAP-imaging as a potentially “disruptive” modality compared to FDG PET/CT. The broader application of FAPI PET/CT has gained momentum, shaping a new narrative in oncological imaging and beyond. FAPI PET/CT is now increasingly recognized as a novel imaging agent that does not aim to replace FDG PET/CT, but rather supports it by enhancing diagnostic accuracy in specific sub-cohort of tumor entities, where FDG PET/CT tends to underperform. Several FAP-derivates- such as FAPI-04, FAPI-46, FAPI-74 for PET imaging as well as FAPI-34 for SPECT imaging were rapidly introduced into clinical practice. To date, FAP-imaging agents have steadily paved their way into clinical practice, particularly in tumor entities such as pancreatic ductal adenocarcinoma, gastroesophageal cancers, and hepatocellular carcinoma. Even in lung cancer, where FDG PET/CT has long held a well-established and clinically robust role, FAPI PET/CT has quickly emerged as a strong competitor, especially in case of lung adenocarcinoma. FAPI PET/CT has been gaining increasing acceptance beyond academic and scientific field as a tool for improved oncological imaging, while FAP theranostics is still in the elaboration and early translation. In contrast to imaging probes, FAP-derivates for therapy require a rather long residence (>48 h) time following successful target-binding at the cancer-associated fibroblast or FAP-positive tumor cells to enable the radiotoxic effect (beta- and alpha-emitter) and deliver enough LET to the cancer microenvironment. Meanwhile, FAP-based imaging probes are advancing into the clinical application, with Phase-II/III clinical trials expected as early as Q4/2025 (NCT07217704 & NCT07217717). In contrast, FAP-targeted therapeutics remain in the Phase-I or proof-of-concept stage but brings hope for patients with systemic disease who are left out and urgently need additional innovation drives beyond the stand
{"title":"Current status of FAP therapy in solid tumors","authors":"Sophie C. Siegmund , Emil Novruzov , Eduards Mamlins , Yuriko Mori , Sven Otto , Martin Canis , Tadashi Watabe , Richard P. Baum , Rudolf A. Werner , Frederik L. Giesel","doi":"10.1053/j.semnuclmed.2025.11.022","DOIUrl":"10.1053/j.semnuclmed.2025.11.022","url":null,"abstract":"<div><div>FAP-ligands as novel cancer radiopharmaceuticals in nuclear medicine have been recently translated successfully into the clinical space. Particularly small molecules (i.e. FAPI-46, FAPI-74) and peptides (i.e. FAP-2286, DOTAGA.SA.FAPi) seem to be some of the most promising molecular probes for imaging and therapy. Back in 2019, there have been slight reservations about adopting this new imaging probe, after the decades of the solidly established role of FDG PET/CT in oncological imaging. At that time, it was expected that these novel ligands might challenge Onco-PET as new cornerstones in the individualized tumor staging and even beyond. However, FAP-targeted imaging is today not intended to replace FDG PET/CT, but rather to complement cancer imaging and therapy, where cancer subtypes exhibit low glucose metabolism which often leads to moderate or very insufficient FDG uptake. Recently, numerous FAP-imaging studies -ranging from single-case reports to larger patient cohorts and even prospective trials have reinforced the empirical understanding of FAP-imaging as a potentially “disruptive” modality compared to FDG PET/CT. The broader application of FAPI PET/CT has gained momentum, shaping a new narrative in oncological imaging and beyond. FAPI PET/CT is now increasingly recognized as a novel imaging agent that does not aim to replace FDG PET/CT, but rather supports it by enhancing diagnostic accuracy in specific sub-cohort of tumor entities, where FDG PET/CT tends to underperform. Several FAP-derivates- such as FAPI-04, FAPI-46, FAPI-74 for PET imaging as well as FAPI-34 for SPECT imaging were rapidly introduced into clinical practice. To date, FAP-imaging agents have steadily paved their way into clinical practice, particularly in tumor entities such as pancreatic ductal adenocarcinoma, gastroesophageal cancers, and hepatocellular carcinoma. Even in lung cancer, where FDG PET/CT has long held a well-established and clinically robust role, FAPI PET/CT has quickly emerged as a strong competitor, especially in case of lung adenocarcinoma. FAPI PET/CT has been gaining increasing acceptance beyond academic and scientific field as a tool for improved oncological imaging, while FAP theranostics is still in the elaboration and early translation. In contrast to imaging probes, FAP-derivates for therapy require a rather long residence (>48 h) time following successful target-binding at the cancer-associated fibroblast or FAP-positive tumor cells to enable the radiotoxic effect (beta- and alpha-emitter) and deliver enough LET to the cancer microenvironment. Meanwhile, FAP-based imaging probes are advancing into the clinical application, with Phase-II/III clinical trials expected as early as Q4/2025 (NCT07217704 & NCT07217717). In contrast, FAP-targeted therapeutics remain in the Phase-I or proof-of-concept stage but brings hope for patients with systemic disease who are left out and urgently need additional innovation drives beyond the stand","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"56 1","pages":"Pages 40-52"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-11-28DOI: 10.1053/j.semnuclmed.2025.11.008
Yunze Xie , Yingying Deng , Eric B. Cruz , Prasanta Kumar Pradhan , Keon Wook Kang , Akram Al-ibraheem , Jiefu Zheng , Hongcheng Shi
Colorectal cancer (CRC) remains one of the most common and deadly malignancies worldwide. Accurate diagnosis, staging, and treatment monitoring are critical for optimizing patient outcomes. Although 18F-FDG PET/CT is widely utilized in CRC imaging, its diagnostic accuracy can be limited by variable avidity across histologic subtypes and by physiological bowel uptake. Fibroblast activation protein (FAP)–targeted positron emission tomography (FAPI PET/CT) has recently emerged as a promising molecular imaging modality that visualizes cancer-associated fibroblasts (CAFs) within the tumor microenvironment. Compared with FDG, FAPI PET/CT provides markedly improved tumor-to-background contrast and higher sensitivity in detecting both primary and metastatic CRC lesions. Beyond its diagnosis and staging utility, FAPI PET/CT offers valuable potential for therapy guidance, treatment response assessment, and prognostic evaluation. Integration with theranostic approaches further enables a comprehensive “see-and-treat”paradigm. FAPI PET/CT represents a transformative advance in CRC management, offering high-contrast, noninvasive visualization of tumor–stroma interactions and facilitating personalized treatment strategies. While current evidence remains preliminary and largely based on small-scale studies, ongoing clinical trials and technological innovations are expected to further define and expand its clinical applications in colorectal cancer.
{"title":"Clinical Utility of FAPI PET/CT in Diagnosis, Staging, and Response Assessment of Colorectal Cancer","authors":"Yunze Xie , Yingying Deng , Eric B. Cruz , Prasanta Kumar Pradhan , Keon Wook Kang , Akram Al-ibraheem , Jiefu Zheng , Hongcheng Shi","doi":"10.1053/j.semnuclmed.2025.11.008","DOIUrl":"10.1053/j.semnuclmed.2025.11.008","url":null,"abstract":"<div><div>Colorectal cancer (CRC) remains one of the most common and deadly malignancies worldwide. Accurate diagnosis, staging, and treatment monitoring are critical for optimizing patient outcomes. Although <sup>18</sup>F-FDG PET/CT is widely utilized in CRC imaging, its diagnostic accuracy can be limited by variable avidity across histologic subtypes and by physiological bowel uptake. Fibroblast activation protein (FAP)–targeted positron emission tomography (FAPI PET/CT) has recently emerged as a promising molecular imaging modality that visualizes cancer-associated fibroblasts (CAFs) within the tumor microenvironment. Compared with FDG, FAPI PET/CT provides markedly improved tumor-to-background contrast and higher sensitivity in detecting both primary and metastatic CRC lesions. Beyond its diagnosis and staging utility, FAPI PET/CT offers valuable potential for therapy guidance, treatment response assessment, and prognostic evaluation. Integration with theranostic approaches further enables a comprehensive “see-and-treat”paradigm. FAPI PET/CT represents a transformative advance in CRC management, offering high-contrast, noninvasive visualization of tumor–stroma interactions and facilitating personalized treatment strategies. While current evidence remains preliminary and largely based on small-scale studies, ongoing clinical trials and technological innovations are expected to further define and expand its clinical applications in colorectal cancer.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"56 1","pages":"Pages 53-61"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145638102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-12-17DOI: 10.1053/j.semnuclmed.2025.11.021
Qaid Ahmed Shagera , Ayça Arçay Öztürk , Kim M. Pabst , Eléonore Longton , Jean-Pascal H. Machiels , Olivier Gheysens , Sandra Nuyts
Head and neck cancers (HNCs) represent a heterogeneous group of malignancies, predominantly composed of squamous cell carcinoma. Radiotherapy (RT), either alone or concurrently with chemotherapy, remains a central component of definitive and adjuvant treatment in HNCs. The success of radiotherapy depends on precise target volume delineation, which relies heavily on advanced imaging techniques. Positron emission tomography with fluorodeoxyglucose (FDG-PET) is well-established in RT planning workflows and endorsed by international guidelines. Recent advances in molecular imaging using fibroblast activation protein inhibitors (FAPI) targeting PET tracers offer improved tumor visualization and target delineation with early studies demonstrating more distinct tumor margins and improved diagnostic performance compared with FDG PET in HNCs. These advantages align with the critical need for highly reliable imaging in a disease site where complex anatomy complicates RT delivery. Early findings suggest a promising role for FAPI PET, in refining gross tumor volume (GTV) delineation and complementing current RT workflows. Despite the promising findings, current evidence is limited to small, primarily single-center cohorts, some with heterogeneous tumor subtypes, and the absence of prospective outcome-based validation. In addition, the utility of FAPI PET in post-RT response assessment and the optimal timing of imaging has yet to be clear defined. Rigorous, methodologically well-designed prospective studies are needed to establish the clinical value, prognostic significance, and impact of FAPI PET on radiotherapy outcomes in HNCs.
{"title":"FAPI PET imaging value in radiotherapy planning and assessment in head and neck cancers","authors":"Qaid Ahmed Shagera , Ayça Arçay Öztürk , Kim M. Pabst , Eléonore Longton , Jean-Pascal H. Machiels , Olivier Gheysens , Sandra Nuyts","doi":"10.1053/j.semnuclmed.2025.11.021","DOIUrl":"10.1053/j.semnuclmed.2025.11.021","url":null,"abstract":"<div><div>Head and neck cancers (HNCs) represent a heterogeneous group of malignancies, predominantly composed of squamous cell carcinoma. Radiotherapy (RT), either alone or concurrently with chemotherapy, remains a central component of definitive and adjuvant treatment in HNCs. The success of radiotherapy depends on precise target volume delineation, which relies heavily on advanced imaging techniques. Positron emission tomography with fluorodeoxyglucose (FDG-PET) is well-established in RT planning workflows and endorsed by international guidelines. Recent advances in molecular imaging using fibroblast activation protein inhibitors (FAPI) targeting PET tracers offer improved tumor visualization and target delineation with early studies demonstrating more distinct tumor margins and improved diagnostic performance compared with FDG PET in HNCs. These advantages align with the critical need for highly reliable imaging in a disease site where complex anatomy complicates RT delivery. Early findings suggest a promising role for FAPI PET, in refining gross tumor volume (GTV) delineation and complementing current RT workflows. Despite the promising findings, current evidence is limited to small, primarily single-center cohorts, some with heterogeneous tumor subtypes, and the absence of prospective outcome-based validation. In addition, the utility of FAPI PET in post-RT response assessment and the optimal timing of imaging has yet to be clear defined. Rigorous, methodologically well-designed prospective studies are needed to establish the clinical value, prognostic significance, and impact of FAPI PET on radiotherapy outcomes in HNCs.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"56 1","pages":"Pages 62-71"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145782564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-12-13DOI: 10.1053/j.semnuclmed.2025.11.014
Savvas Frangos , Evanthia Giannoula , Ioannis Iakovou
Differentiated thyrοid carcinoma (DTC) is the most common endocrine malignancy, generally associated with excellent long-term survival. Hοwever, a subset of patients develοps advanced disease (aDTC), particularly when refractοry to radioactive iodine (RAIR), which poses significant therapeutic challenges and wοrse outcomes. Accurate, individualized assessment οf treatment respοnse is essential for optimizing patient management. This review summarizes current principles fοr biοmarker- and imaging-based evaluation of aDTC. Serum thyroglobulin (Tg) and anti-thyroglobulin antibodies (TgAb), including their dynamic changes οver time, remain central biomarkers for detecting persistent, recurrent, or metastatic disease. Mοlecular profiling, including BRAF, TERT, and RAS mutatiοns, provides additional prognοstic and predictive information and guides the use of targeted therapies. Imaging modalities, including post-therapy radioiodine whole-body scans (WBS), single-phοton emission computed tomography/computed tomography (SPECT/CT), 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), and emerging tracers such as 68Ga-DOTATATE and PSMA PET/CT, οffer complementary anatomical and functional data for respοnse assessment, particularly in RAIR or metabοlically active disease. Current guidelines recommend integrating biomarker trends with imaging findings within a dynamic risk stratification framework to guide individualized treatment decisiοns. Despite well-established recοmmendations, real-world application remains variable due to patient heterogeneity and center-specific resources. Emerging imaging modalities, quantitative PET metrics, and artificial intelligence (ΑΙ) –assisted approaches hold prοmise for enhancing prognostic accuracy and personalizing fοllow-up and therapy.
Cοnclusions: Integrating biomarkers, molecular profiling, and advanced imaging within a dynamic, patient-centered framework is essential for accurate response assessment and optimal management of advanced differentiated thyroid carcinoma.
分化甲状腺癌（DTC）是最常见的内分泌恶性肿瘤，通常具有良好的长期生存率。然而，一部分患者会发展为晚期疾病（aDTC），特别是当他们尝试使用放射性碘（RAIR）时，这给治疗带来了重大挑战，并降低了结果。准确、个性化的治疗反应评估对于优化患者管理至关重要。本文综述了现行的基于o (o)或o (o)生物标志物和o (o)成像评价aDTC的原则。血清甲状腺球蛋白（Tg）和抗甲状腺球蛋白抗体（TgAb），包括它们随时间的动态变化，仍然是检测持续性、复发性或转移性疾病的核心生物标志物。分子分析，包括BRAF、TERT和RAS突变，提供了额外的预测和预测信息，并指导靶向治疗的使用。成像方式，包括治疗后放射性碘全身扫描（WBS），单磷- o -t发射计算机断层扫描/计算机断层扫描（SPECT/CT）， 18f -氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描（18F-FDG PET/CT），以及新兴的示踪剂，如68Ga-DOTATATE和PSMA PET/CT，为反应性评估提供了补充的解剖和功能数据，特别是在RAIR或代谢- o -活跃疾病中。目前的指南建议在动态风险分层框架内整合生物标志物趋势和成像结果，以指导个性化治疗决策。尽管有完善的reο推荐，但由于患者的异质性和中心特定的资源，实际应用仍然存在差异。新兴的成像模式、定量PET指标和人工智能（ΑΙ）辅助方法有望提高预后准确性和个性化的随访和治疗。结论：在一个动态的、以患者为中心的框架内整合生物标志物、分子谱和先进的成像技术，对于准确评估晚期分化型甲状腺癌的疗效和优化治疗至关重要。
{"title":"Response assessment in advanced differentiated thyroid cancer","authors":"Savvas Frangos , Evanthia Giannoula , Ioannis Iakovou","doi":"10.1053/j.semnuclmed.2025.11.014","DOIUrl":"10.1053/j.semnuclmed.2025.11.014","url":null,"abstract":"<div><div>Differentiated thyrοid carcinoma (DTC) is the most common endocrine malignancy, generally associated with excellent long-term survival. Hοwever, a subset of patients develοps advanced disease (aDTC), particularly when refractοry to radioactive iodine (RAIR), which poses significant therapeutic challenges and wοrse outcomes. Accurate, individualized assessment οf treatment respοnse is essential for optimizing patient management. This review summarizes current principles fοr biοmarker- and imaging-based evaluation of aDTC. Serum thyroglobulin (Tg) and anti-thyroglobulin antibodies (TgAb), including their dynamic changes οver time, remain central biomarkers for detecting persistent, recurrent, or metastatic disease. Mοlecular profiling, including BRAF, TERT, and RAS mutatiοns, provides additional prognοstic and predictive information and guides the use of targeted therapies. Imaging modalities, including post-therapy radioiodine whole-body scans (WBS), single-phοton emission computed tomography/computed tomography (SPECT/CT), <sup>18</sup>F-fluorodeoxyglucose positron emission tomography/computed tomography (<sup>18</sup>F-FDG PET/CT), and emerging tracers such as <sup>68</sup>Ga-DOTATATE and PSMA PET/CT, οffer complementary anatomical and functional data for respοnse assessment, particularly in RAIR or metabοlically active disease. Current guidelines recommend integrating biomarker trends with imaging findings within a dynamic risk stratification framework to guide individualized treatment decisiοns. Despite well-established recοmmendations, real-world application remains variable due to patient heterogeneity and center-specific resources. Emerging imaging modalities, quantitative PET metrics, and artificial intelligence (ΑΙ) –assisted approaches hold prοmise for enhancing prognostic accuracy and personalizing fοllow-up and therapy.</div><div>Cοnclusions: Integrating biomarkers, molecular profiling, and advanced imaging within a dynamic, patient-centered framework is essential for accurate response assessment and optimal management of advanced differentiated thyroid carcinoma.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"56 1","pages":"Pages 31-39"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-12-29DOI: 10.1053/j.semnuclmed.2025.11.011
Christiane Wiefels , Luis Eduardo Juárez-Orozco , Pietro Selemo Craviolatti , Oleksandr Diahiliev , Amir Eskander , Raffaele Giubbini , Elisa Milan , Weihua Zhou , Ganesan Karthikeyan , Amelia Jimenez-Heffernan , Amalia Peix , Angelin Apostol , Anita Brink , Maurizio Dondi , Diana Paez
Artificial intelligence (AI) is increasingly permeating nuclear cardiology and offers the possibility to enhance diagnostic accuracy, prognostic stratification, and operational efficiency. AI is demonstrating applicability across the imaging workflow—from individualized patient selection and adaptive image reconstruction to denoising of low-dose datasets, automated attenuation and motion correction, calcium scoring, and the integration of imaging with clinical and functional variables for enhanced diagnosis and comprehensive risk assessment.
But the translational trajectory of AI in nuclear cardiology is challenged by the lag in fundamental AI knowledge among researchers and clinicians, the quality of the target data regarding heterogeneity in acquisition protocols, scanner platforms, and patient populations, and by infrastructural disparities that constrain the generation of large, representative datasets needed for training and validation, particularly in low-resource settings. Additionally, necessary regulatory and legal frameworks remain in early stages of harmonization.
This white paper, developed by an International Atomic Energy Agency (IAEA) working group, provides a succinct overview of the technical basis, areas of deployment, clinical value and unmet challenges of AI in nuclear cardiology. It makes punctual suggestions to aid maturation in this area while maintaining a sober interaction with the overwhelming nature of the field. These include promoting standardized acquisition and reporting practices, establishing globally representative reference datasets, promoting imaging multimodality frameworks and developing AI-proficient clinical and technical personnel. Under these conditions, AI may meaningfully enhance the diagnostic and prognostic value of nuclear cardiology while supporting equitable implementation and preserving clinical accountability.
{"title":"Artificial intelligence in nuclear cardiology: Technical perspectives, strategic directions, and recommendations from an IAEA expert working group","authors":"Christiane Wiefels , Luis Eduardo Juárez-Orozco , Pietro Selemo Craviolatti , Oleksandr Diahiliev , Amir Eskander , Raffaele Giubbini , Elisa Milan , Weihua Zhou , Ganesan Karthikeyan , Amelia Jimenez-Heffernan , Amalia Peix , Angelin Apostol , Anita Brink , Maurizio Dondi , Diana Paez","doi":"10.1053/j.semnuclmed.2025.11.011","DOIUrl":"10.1053/j.semnuclmed.2025.11.011","url":null,"abstract":"<div><div>Artificial intelligence (AI) is increasingly permeating nuclear cardiology and offers the possibility to enhance diagnostic accuracy, prognostic stratification, and operational efficiency. AI is demonstrating applicability across the imaging workflow—from individualized patient selection and adaptive image reconstruction to denoising of low-dose datasets, automated attenuation and motion correction, calcium scoring, and the integration of imaging with clinical and functional variables for enhanced diagnosis and comprehensive risk assessment.</div><div>But the translational trajectory of AI in nuclear cardiology is challenged by the lag in fundamental AI knowledge among researchers and clinicians, the quality of the target data regarding heterogeneity in acquisition protocols, scanner platforms, and patient populations, and by infrastructural disparities that constrain the generation of large, representative datasets needed for training and validation, particularly in low-resource settings. Additionally, necessary regulatory and legal frameworks remain in early stages of harmonization.</div><div>This white paper, developed by an International Atomic Energy Agency (IAEA) working group, provides a succinct overview of the technical basis, areas of deployment, clinical value and unmet challenges of AI in nuclear cardiology. It makes punctual suggestions to aid maturation in this area while maintaining a sober interaction with the overwhelming nature of the field. These include promoting standardized acquisition and reporting practices, establishing globally representative reference datasets, promoting imaging multimodality frameworks and developing AI-proficient clinical and technical personnel. Under these conditions, AI may meaningfully enhance the diagnostic and prognostic value of nuclear cardiology while supporting equitable implementation and preserving clinical accountability.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"56 1","pages":"Pages 119-131"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145865121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2026-01-09DOI: 10.1053/j.semnuclmed.2025.12.001
Ishita Sen, Dharmender Malik, Parul Thakral
Prostate cancer remains a major global health burden, and the integration of PSMA-targeted PET imaging and radioligand therapy has transformed diagnostic and therapeutic strategies for advanced disease. Traditional response assessment tools—such as PSA kinetics, CT, bone scans, and composite criteria like PCWG3 or RECIST—are limited by PSA flare phenomena, inability to evaluate bone-only disease, and lack of sensitivity for early metastatic changes. To address these limitations, the Response Evaluation Criteria in PSMA PET/CT (RECIP 1.0) was developed as the first evidence-based framework leveraging PSMA PET imaging for treatment response evaluation. RECIP 1.0 incorporates changes in PSMA-positive total tumour volume and the appearance of new lesions, enabling stratification into complete response, partial response, stable disease, or progressive disease. It has demonstrated strong prognostic value for overall and progression-free survival and supports standardized reporting essential for clinical trials. A visual RECIP method further enhances feasibility in routine practice, showing excellent concordance with quantitative software-based segmentation. Although challenges remain, particularly the labor-intensive nature of tumour segmentation and variability across imaging protocols emerging AI-based automated tools are poised to streamline RECIP implementation. As PSMA-based theranostics continue to expand, RECIP 1.0 offers a robust and clinically meaningful framework for response assessment.
{"title":"Clinical implementation of RECIP 1.0","authors":"Ishita Sen, Dharmender Malik, Parul Thakral","doi":"10.1053/j.semnuclmed.2025.12.001","DOIUrl":"10.1053/j.semnuclmed.2025.12.001","url":null,"abstract":"<div><div>Prostate cancer remains a major global health burden, and the integration of PSMA-targeted PET imaging and radioligand therapy has transformed diagnostic and therapeutic strategies for advanced disease. Traditional response assessment tools—such as PSA kinetics, CT, bone scans, and composite criteria like PCWG3 or RECIST—are limited by PSA flare phenomena, inability to evaluate bone-only disease, and lack of sensitivity for early metastatic changes. To address these limitations, the Response Evaluation Criteria in PSMA PET/CT (RECIP 1.0) was developed as the first evidence-based framework leveraging PSMA PET imaging for treatment response evaluation. RECIP 1.0 incorporates changes in PSMA-positive total tumour volume and the appearance of new lesions, enabling stratification into complete response, partial response, stable disease, or progressive disease. It has demonstrated strong prognostic value for overall and progression-free survival and supports standardized reporting essential for clinical trials. A visual RECIP method further enhances feasibility in routine practice, showing excellent concordance with quantitative software-based segmentation. Although challenges remain, particularly the labor-intensive nature of tumour segmentation and variability across imaging protocols emerging AI-based automated tools are poised to streamline RECIP implementation. As PSMA-based theranostics continue to expand, RECIP 1.0 offers a robust and clinically meaningful framework for response assessment.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"56 1","pages":"Pages 5-8"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2026-01-13DOI: 10.1053/j.semnuclmed.2025.12.004
{"title":"Letter from the Editors","authors":"","doi":"10.1053/j.semnuclmed.2025.12.004","DOIUrl":"10.1053/j.semnuclmed.2025.12.004","url":null,"abstract":"","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"56 1","pages":"Pages 1-4"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145985339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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