Pub Date : 2026-01-29DOI: 10.2967/jnumed.126.272054
Jason S Lewis,Johannes Czernin
{"title":"Leading Through Change: Reflections from Jason Lewis.","authors":"Jason S Lewis,Johannes Czernin","doi":"10.2967/jnumed.126.272054","DOIUrl":"https://doi.org/10.2967/jnumed.126.272054","url":null,"abstract":"","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073081","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 : 2026-01-29DOI: 10.2967/jnumed.125.271039
Mark J Macsuka,Brandon Driscoll,Ivan W T Yeung,Julia Publicover,Ur Metser,Rosalyn Juergens,Sten D Myrehaug,David Laidley,Rebecca K Wong,Daniel R McGowan,Katherine A Vallis
The aim of this study was to use image-derived dose metrics to predict the radiologic response of neuroendocrine tumors treated with [177Lu]Lu-DOTATATE. Particular focus was given to the evaluation of cyclic changes in absorbed dose per administered activity (AD/AA) as a potential prognostic factor. Methods: Data from 73 patients enrolled in the multicenter OZM-067 trial (NCT02743741) were analyzed. All patients who received 4 cycles of [177Lu]Lu-DOTATATE and underwent SPECT/CT imaging at 3 time points after each treatment were included. Tumor dosimetry was based on semiautomatic adaptive-threshold segmentations and recovery coefficient-based partial-volume correction; tumors smaller than 10 cm³ were excluded. If multiple tumors were segmented per patient, the mean absorbed dose (AD) and AD/AA were recorded at each cycle. Radiologic response was assessed using RECIST 1.1 criteria. Results: A significant decrease in AD/AA across cycles was observed, with a median decline of approximately 10% per cycle. Within this cohort, 28 patients had a partial response, 33 had stable disease, and 12 experienced disease progression. Responders exhibited a higher mean cumulative AD and greater decreases in AD/AA in successive cycles when compared with nonresponders. These metrics were uncorrelated predictors of response (P = 0.64). Notably, all 8 patients with an AD of at least 100 Gy and a decrease of at least 50% in AD/AA between cycles 1 and 4 were responders. Quantitative models combining AD and changes in AD/AA achieved an area under the receiver-operating-characteristic curve of 0.78. Conclusion: Both AD and changes in AD/AA were independently associated with radiologic response to [177Lu]Lu-DOTATATE in patients with neuroendocrine tumors. The consistent decrease in AD/AA over a course of therapy suggests a potential imaging biomarker that could inform adaptive treatment strategies, which should be further evaluated in a prospective setting and considered when designing dosimetry-guided [177Lu]Lu-DOTATATE trials.
{"title":"Cumulative Absorbed Dose and Successive Cyclic Reduction in Absorbed Dose Predict Response to 177Lu-DOTATATE in Neuroendocrine Tumors.","authors":"Mark J Macsuka,Brandon Driscoll,Ivan W T Yeung,Julia Publicover,Ur Metser,Rosalyn Juergens,Sten D Myrehaug,David Laidley,Rebecca K Wong,Daniel R McGowan,Katherine A Vallis","doi":"10.2967/jnumed.125.271039","DOIUrl":"https://doi.org/10.2967/jnumed.125.271039","url":null,"abstract":"The aim of this study was to use image-derived dose metrics to predict the radiologic response of neuroendocrine tumors treated with [177Lu]Lu-DOTATATE. Particular focus was given to the evaluation of cyclic changes in absorbed dose per administered activity (AD/AA) as a potential prognostic factor. Methods: Data from 73 patients enrolled in the multicenter OZM-067 trial (NCT02743741) were analyzed. All patients who received 4 cycles of [177Lu]Lu-DOTATATE and underwent SPECT/CT imaging at 3 time points after each treatment were included. Tumor dosimetry was based on semiautomatic adaptive-threshold segmentations and recovery coefficient-based partial-volume correction; tumors smaller than 10 cm³ were excluded. If multiple tumors were segmented per patient, the mean absorbed dose (AD) and AD/AA were recorded at each cycle. Radiologic response was assessed using RECIST 1.1 criteria. Results: A significant decrease in AD/AA across cycles was observed, with a median decline of approximately 10% per cycle. Within this cohort, 28 patients had a partial response, 33 had stable disease, and 12 experienced disease progression. Responders exhibited a higher mean cumulative AD and greater decreases in AD/AA in successive cycles when compared with nonresponders. These metrics were uncorrelated predictors of response (P = 0.64). Notably, all 8 patients with an AD of at least 100 Gy and a decrease of at least 50% in AD/AA between cycles 1 and 4 were responders. Quantitative models combining AD and changes in AD/AA achieved an area under the receiver-operating-characteristic curve of 0.78. Conclusion: Both AD and changes in AD/AA were independently associated with radiologic response to [177Lu]Lu-DOTATATE in patients with neuroendocrine tumors. The consistent decrease in AD/AA over a course of therapy suggests a potential imaging biomarker that could inform adaptive treatment strategies, which should be further evaluated in a prospective setting and considered when designing dosimetry-guided [177Lu]Lu-DOTATATE trials.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"93 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073008","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 : 2026-01-29DOI: 10.2967/jnumed.125.271459
Joni J Nijveldt,Siri Af Burén,Thuy A Tran,Emma Jussing,Joachim N Nilsson,Anna Kistner,Rimma Axelsson,Jonas Bergh,Johan Hartman,Antonios Tzortzakakis,Renske Altena
Immune checkpoint inhibitors combined with chemotherapy are established as first-line therapy for patients with programmed death ligand 1 (PD-L1)-positive metastatic triple-negative breast cancer (mTNBC). We evaluated whether immuno-PET using [89Zr]Zr-atezolizumab could more accurately identify patients with mTNBC who may benefit from immune checkpoint inhibitor therapy. Methods: Three patients with mTNBC underwent [89Zr]Zr-atezolizumab PET/CT followed by a biopsy of a targeted metastatic lesion. Patients received atezolizumab plus chemotherapy if either immunohistochemistry of the metastatic lesion or PET imaging showed PD-L1 positivity. Results: All patients had tracer-avid metastatic lesions on PET. Two of 3 biopsied, tracer-avid lesions were PD-L1 negative on immunohistochemistry. Intraindividual heterogeneity in tracer uptake was noted. All patients were treated with atezolizumab plus chemotherapy, with all demonstrating an initial response. Conclusion: A work-up with [89Zr]Zr-atezolizumab immuno-PET is clinically feasible. This molecular imaging-based strategy holds potential as a noninvasive tool to more accurately identify patients with mTNBC who may benefit from immune checkpoint inhibitor therapy.
{"title":"Feasibility of [89Zr]Zr-Atezolizumab Immuno-PET for PD-L1 Quantification in the Clinical Work-up of Metastatic Triple-Negative Breast Cancer.","authors":"Joni J Nijveldt,Siri Af Burén,Thuy A Tran,Emma Jussing,Joachim N Nilsson,Anna Kistner,Rimma Axelsson,Jonas Bergh,Johan Hartman,Antonios Tzortzakakis,Renske Altena","doi":"10.2967/jnumed.125.271459","DOIUrl":"https://doi.org/10.2967/jnumed.125.271459","url":null,"abstract":"Immune checkpoint inhibitors combined with chemotherapy are established as first-line therapy for patients with programmed death ligand 1 (PD-L1)-positive metastatic triple-negative breast cancer (mTNBC). We evaluated whether immuno-PET using [89Zr]Zr-atezolizumab could more accurately identify patients with mTNBC who may benefit from immune checkpoint inhibitor therapy. Methods: Three patients with mTNBC underwent [89Zr]Zr-atezolizumab PET/CT followed by a biopsy of a targeted metastatic lesion. Patients received atezolizumab plus chemotherapy if either immunohistochemistry of the metastatic lesion or PET imaging showed PD-L1 positivity. Results: All patients had tracer-avid metastatic lesions on PET. Two of 3 biopsied, tracer-avid lesions were PD-L1 negative on immunohistochemistry. Intraindividual heterogeneity in tracer uptake was noted. All patients were treated with atezolizumab plus chemotherapy, with all demonstrating an initial response. Conclusion: A work-up with [89Zr]Zr-atezolizumab immuno-PET is clinically feasible. This molecular imaging-based strategy holds potential as a noninvasive tool to more accurately identify patients with mTNBC who may benefit from immune checkpoint inhibitor therapy.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"74 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073141","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}
We developed a new C-X-C chemokine receptor 4 (CXCR4)-targeting radiolabeled peptide, [68Ga]Ga/[177Lu]Lu-BL34, using a novel and potent cyclic peptide based on structure-activity relationship studies of LY2510924. Methods: Candidate inhibitors were designed on the basis of structure-activity studies and synthesized using solid-phase techniques, and their CXCR4 binding was assessed using a cell-based assay. An optimized cyclic peptide sequence was modified with a Lys-cysteic acid linker and DOTA chelator to make BL34. Other analogs possessing ornithine or diaminopimelic acid linkers were also synthesized and assessed. All radiotracers were assessed in mice engrafted with a mantle cell lymphoma model (Z138) via PET/SPECT imaging and biodistribution studies. Therapeutic efficacy of [177Lu]Lu-BL34 was assessed in Z138-engrafted mice with groups of 30 and 60 MBq and a control. Results: The optimized cyclic peptide showed a 3-fold improvement in CXCR4 binding compared with that of LY2510924. [68Ga]Ga-BL34 showed high imaging contrast for the tumor at 1 and 2 h after injection. Biodistribution studies confirmed these results, with an uptake of 15.1 ± 3.1 %ID/g in the tumor at 1 h after injection and primarily renal excretion with a kidney uptake of 2.4 ± 0.4 %ID/g. SPECT imaging of [177Lu]Lu-BL34 showed similar results, with rapid renal excretion of [177Lu]Lu-BL34 from nontarget organs and relatively high uptake in tumors up to 72 h after injection. Biodistribution studies confirmed high tumor uptake at all time points, with low uptake across all nontarget organs. Blocking studies with LY2510924 further confirmed specificity. Therapy studies showed dose-dependent survival benefit with [177Lu]Lu-BL34 treatment, with metastatic recurrence in the treatment groups. Changing the side chain length at the linker attachment site did not affect the biodistribution or tumor uptake. Conclusion: We report a new CXCR4-targeting pharmacophore that can be used as a radiotheranostic. [68Ga]Ga-BL34 and [177Lu]Lu-BL34 showed excellent imaging and therapeutic properties in preclinical studies and are promising candidates for clinical translation.
{"title":"Development of an Optimized CXCR4-Targeting Theranostic Pair.","authors":"Daniel Kwon,Ingrid Bloise,Zhengxing Zhang,Nadine Colpo,Ryan Wilson,Ruiyan Tan,Helen Merkens,Jutta Zeisler,Joseph Lau,Kuo-Shyan Lin,François Bénard","doi":"10.2967/jnumed.125.269933","DOIUrl":"https://doi.org/10.2967/jnumed.125.269933","url":null,"abstract":"We developed a new C-X-C chemokine receptor 4 (CXCR4)-targeting radiolabeled peptide, [68Ga]Ga/[177Lu]Lu-BL34, using a novel and potent cyclic peptide based on structure-activity relationship studies of LY2510924. Methods: Candidate inhibitors were designed on the basis of structure-activity studies and synthesized using solid-phase techniques, and their CXCR4 binding was assessed using a cell-based assay. An optimized cyclic peptide sequence was modified with a Lys-cysteic acid linker and DOTA chelator to make BL34. Other analogs possessing ornithine or diaminopimelic acid linkers were also synthesized and assessed. All radiotracers were assessed in mice engrafted with a mantle cell lymphoma model (Z138) via PET/SPECT imaging and biodistribution studies. Therapeutic efficacy of [177Lu]Lu-BL34 was assessed in Z138-engrafted mice with groups of 30 and 60 MBq and a control. Results: The optimized cyclic peptide showed a 3-fold improvement in CXCR4 binding compared with that of LY2510924. [68Ga]Ga-BL34 showed high imaging contrast for the tumor at 1 and 2 h after injection. Biodistribution studies confirmed these results, with an uptake of 15.1 ± 3.1 %ID/g in the tumor at 1 h after injection and primarily renal excretion with a kidney uptake of 2.4 ± 0.4 %ID/g. SPECT imaging of [177Lu]Lu-BL34 showed similar results, with rapid renal excretion of [177Lu]Lu-BL34 from nontarget organs and relatively high uptake in tumors up to 72 h after injection. Biodistribution studies confirmed high tumor uptake at all time points, with low uptake across all nontarget organs. Blocking studies with LY2510924 further confirmed specificity. Therapy studies showed dose-dependent survival benefit with [177Lu]Lu-BL34 treatment, with metastatic recurrence in the treatment groups. Changing the side chain length at the linker attachment site did not affect the biodistribution or tumor uptake. Conclusion: We report a new CXCR4-targeting pharmacophore that can be used as a radiotheranostic. [68Ga]Ga-BL34 and [177Lu]Lu-BL34 showed excellent imaging and therapeutic properties in preclinical studies and are promising candidates for clinical translation.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"82 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072933","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 : 2026-01-22DOI: 10.2967/jnumed.125.271019
Ryota Satoh,Farwa Ali,Dennis W Dickson,Val J Lowe,Keith A Josephs,Jennifer L Whitwell
[18F]flortaucipir PET imaging has shown relatively low sensitivity for detecting four-repeat (4R) tau, which limits its utility in 4R tauopathies such as progressive supranuclear palsy (PSP). Previous studies have suggested that the first component of principal-component analysis includes non-disease-related uptake in non-Alzheimer tauopathies. In this study, we tested the hypothesis that subtracting this component could increase sensitivity to 4R tau using a large PSP cohort. Methods: Prospectively recruited patients with PSP (n = 141; 80 Richardson syndrome, 44 PSP-subcortical, and 17 PSP-cortical variants) and controls (n = 102) underwent [18F]flortaucipir PET. The first principal component (PC1) was extracted from the SUV ratio (SUVR) images of 62 controls and then subtracted from the remaining controls (n = 40) and all PSP patients. We compared the diagnostic performance before and after PC1 subtraction by evaluating SUVR differences between PSP and controls, as well as across PSP clinical variants, and by calculating correlation coefficients between SUVR and the severity of tau pathology. Results: Area under the receiver operating characteristic curves differentiating PSP and controls were improved by PC1 subtraction in the frontal white matter (0.54 to 0.67; P = 0.002) and subcortical (0.69 to 0.87; P < 0.001) regions. In the frontal regions, no differences were observed across PSP clinical variants before PC1 subtraction, whereas the PSP-cortical variant showed an SUVR higher than that of the PSP Richardson syndrome and PSP-subcortical variants after PC1 subtraction (adjusted P < 0.05). A correlation with the severity of tau pathology was observed only in the red nucleus before PC1 subtraction, whereas correlations were observed in the precentral, superior frontal gyrus, and red nucleus after PC1 subtraction (adjusted P < 0.05). Conclusion: Our approach enhanced the diagnostic performance of [18F]flortaucipir PET in PSP and increased sensitivity to 4R tau, suggesting that subtracting the first principal component improves the detectability of subtle 4R tau uptake and the potential utility of [18F]flortaucipir PET imaging for non-Alzheimer tauopathies.
{"title":"Subtracting First Principal Component May Improve 4R Tau Detectability on [18F]Flortaucipir Tau PET.","authors":"Ryota Satoh,Farwa Ali,Dennis W Dickson,Val J Lowe,Keith A Josephs,Jennifer L Whitwell","doi":"10.2967/jnumed.125.271019","DOIUrl":"https://doi.org/10.2967/jnumed.125.271019","url":null,"abstract":"[18F]flortaucipir PET imaging has shown relatively low sensitivity for detecting four-repeat (4R) tau, which limits its utility in 4R tauopathies such as progressive supranuclear palsy (PSP). Previous studies have suggested that the first component of principal-component analysis includes non-disease-related uptake in non-Alzheimer tauopathies. In this study, we tested the hypothesis that subtracting this component could increase sensitivity to 4R tau using a large PSP cohort. Methods: Prospectively recruited patients with PSP (n = 141; 80 Richardson syndrome, 44 PSP-subcortical, and 17 PSP-cortical variants) and controls (n = 102) underwent [18F]flortaucipir PET. The first principal component (PC1) was extracted from the SUV ratio (SUVR) images of 62 controls and then subtracted from the remaining controls (n = 40) and all PSP patients. We compared the diagnostic performance before and after PC1 subtraction by evaluating SUVR differences between PSP and controls, as well as across PSP clinical variants, and by calculating correlation coefficients between SUVR and the severity of tau pathology. Results: Area under the receiver operating characteristic curves differentiating PSP and controls were improved by PC1 subtraction in the frontal white matter (0.54 to 0.67; P = 0.002) and subcortical (0.69 to 0.87; P < 0.001) regions. In the frontal regions, no differences were observed across PSP clinical variants before PC1 subtraction, whereas the PSP-cortical variant showed an SUVR higher than that of the PSP Richardson syndrome and PSP-subcortical variants after PC1 subtraction (adjusted P < 0.05). A correlation with the severity of tau pathology was observed only in the red nucleus before PC1 subtraction, whereas correlations were observed in the precentral, superior frontal gyrus, and red nucleus after PC1 subtraction (adjusted P < 0.05). Conclusion: Our approach enhanced the diagnostic performance of [18F]flortaucipir PET in PSP and increased sensitivity to 4R tau, suggesting that subtracting the first principal component improves the detectability of subtle 4R tau uptake and the potential utility of [18F]flortaucipir PET imaging for non-Alzheimer tauopathies.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021556","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 : 2026-01-22DOI: 10.2967/jnumed.125.271452
Dirk Zboralski,Frank Osterkamp,Jan L von Hacht,Anne Bredenbeck,Aileen Höhne,Jeanette Libera-Körner,Jan Ungewiss,Matthias Paschke,Ulrich Reineke,Christiane Smerling
Fibroblast activation protein (FAP) is highly expressed in the tumor microenvironment of many cancer types. Since the discovery of the FAP inhibitor series, which provided high-contrast images in patients, many radiolabeled FAP-targeting agents have been developed, with the cyclic peptide FAP-2286 currently being the most advanced theranostic compound in clinical development. Here, we introduce a novel peptide, 3BP-3940, which has been used to treat patients with cancer on a named-patient basis. Methods: The potency and selectivity of 3BP-3940 were evaluated in biochemical assays. Its biodistribution was assessed in mice and minipigs, and therapeutic efficacy was demonstrated in the HEK-FAP mouse model. Results: 3BP-3940 exhibited high affinity and specificity for FAP, with persistent uptake in HEK-FAP xenograft tumors, leading to strong tumor growth inhibition when radiolabeled with 177Lu. 3BP-3940 showed minimal uptake in normal tissues of mice and minipigs. Conclusion: These findings support the clinical use of 3BP-3940 as a promising FAP-targeting agent for both imaging and radiopharmaceutical therapy in patients with cancer.
{"title":"Preclinical Development of 3BP-3940, a Fibroblast Activation Protein-Targeted Cyclic Peptide-Based Radiotheranostic for Imaging and Therapy.","authors":"Dirk Zboralski,Frank Osterkamp,Jan L von Hacht,Anne Bredenbeck,Aileen Höhne,Jeanette Libera-Körner,Jan Ungewiss,Matthias Paschke,Ulrich Reineke,Christiane Smerling","doi":"10.2967/jnumed.125.271452","DOIUrl":"https://doi.org/10.2967/jnumed.125.271452","url":null,"abstract":"Fibroblast activation protein (FAP) is highly expressed in the tumor microenvironment of many cancer types. Since the discovery of the FAP inhibitor series, which provided high-contrast images in patients, many radiolabeled FAP-targeting agents have been developed, with the cyclic peptide FAP-2286 currently being the most advanced theranostic compound in clinical development. Here, we introduce a novel peptide, 3BP-3940, which has been used to treat patients with cancer on a named-patient basis. Methods: The potency and selectivity of 3BP-3940 were evaluated in biochemical assays. Its biodistribution was assessed in mice and minipigs, and therapeutic efficacy was demonstrated in the HEK-FAP mouse model. Results: 3BP-3940 exhibited high affinity and specificity for FAP, with persistent uptake in HEK-FAP xenograft tumors, leading to strong tumor growth inhibition when radiolabeled with 177Lu. 3BP-3940 showed minimal uptake in normal tissues of mice and minipigs. Conclusion: These findings support the clinical use of 3BP-3940 as a promising FAP-targeting agent for both imaging and radiopharmaceutical therapy in patients with cancer.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021560","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}
Cancer metastasis, particularly to the pleura, signifies advanced disease and poor prognosis. Fibroblast activation protein (FAP), which is highly expressed on cancer-associated fibroblasts, is a promising therapeutic target. This retrospective study investigates the efficacy and safety of the FAP-targeting radiopharmaceutical therapy [177Lu]Lu-FAP-2286 in patients with pleural metastases. Methods: Seventeen patients with FAP-positive pleural metastases from various carcinomas, all previously treated with standard therapies, received a median of 2 cycles of [177Lu]Lu-FAP-2286. Treatment response was assessed using FAP PET/CT, CT, and qualitative FAP SPECT/CT. Overall survival (OS) and progression-free survival were analyzed, and adverse events (AEs) were reported. Results: The disease control rate (nonprogressive disease) was 59%. Median OS was 17.3 mo, and median progression-free survival was 4.1 mo. Patients achieving disease control had a significantly longer OS (20.3 mo) compared with those with progressive disease (6.4 mo, P = 0.004). Response assessments using FAP PERCIST 1.0 and RECIST 1.1 showed a high concordance rate of 86.7%. Treatment was well-tolerated, with no grade 3-4 AEs reported. The most common AEs were manageable grade 1-2 hematologic toxicities. Conclusion: [177Lu]Lu-FAP-2286 therapy demonstrates promising preliminary efficacy and a favorable safety profile in patients with pleural metastases, achieving notable disease control and survival outcomes. This study provides real-world evidence supporting FAP-targeted radiopharmaceutical therapy as a treatment option for this patient population and suggests FAP-based imaging is useful for response monitoring. Larger, prospective studies are warranted to confirm these findings.
{"title":"Initial Results and Clinical Experiences of [177Lu]Lu-FAP-2286 for Pleural Metastases: A Single-Center Retrospective Study.","authors":"Linwei Li,Hongyin Ding,Lingzhi Chen,Wenlu Zheng,Yu Zhang,Yue Chen","doi":"10.2967/jnumed.125.271317","DOIUrl":"https://doi.org/10.2967/jnumed.125.271317","url":null,"abstract":"Cancer metastasis, particularly to the pleura, signifies advanced disease and poor prognosis. Fibroblast activation protein (FAP), which is highly expressed on cancer-associated fibroblasts, is a promising therapeutic target. This retrospective study investigates the efficacy and safety of the FAP-targeting radiopharmaceutical therapy [177Lu]Lu-FAP-2286 in patients with pleural metastases. Methods: Seventeen patients with FAP-positive pleural metastases from various carcinomas, all previously treated with standard therapies, received a median of 2 cycles of [177Lu]Lu-FAP-2286. Treatment response was assessed using FAP PET/CT, CT, and qualitative FAP SPECT/CT. Overall survival (OS) and progression-free survival were analyzed, and adverse events (AEs) were reported. Results: The disease control rate (nonprogressive disease) was 59%. Median OS was 17.3 mo, and median progression-free survival was 4.1 mo. Patients achieving disease control had a significantly longer OS (20.3 mo) compared with those with progressive disease (6.4 mo, P = 0.004). Response assessments using FAP PERCIST 1.0 and RECIST 1.1 showed a high concordance rate of 86.7%. Treatment was well-tolerated, with no grade 3-4 AEs reported. The most common AEs were manageable grade 1-2 hematologic toxicities. Conclusion: [177Lu]Lu-FAP-2286 therapy demonstrates promising preliminary efficacy and a favorable safety profile in patients with pleural metastases, achieving notable disease control and survival outcomes. This study provides real-world evidence supporting FAP-targeted radiopharmaceutical therapy as a treatment option for this patient population and suggests FAP-based imaging is useful for response monitoring. Larger, prospective studies are warranted to confirm these findings.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"382 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021353","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}
Limbic-predominant age-related transactive response DNA-binding protein 43 kDa encephalopathy (LATE) is emerging as a prevalent neurodegenerative disorder in aging populations, mimicking the clinical presentation of Alzheimer disease (AD). This study investigates in vivo [18F]FDG PET and MRI biomarkers in detecting probable LATE neuropathologic change. Methods: We retrospectively analyzed 944 [18F]FDG PET cases referred from cognitive disorder clinics in a tertiary care center. To characterize the LATE and AD findings objectively and quantitatively, we created 3-dimensional stereotactic surface projection PET templates for LATE neuropathologic change (n = 6) and AD neuropathologic change (n = 32) from autopsy-confirmed Alzheimer's Disease Neuroimaging Initiative and University of Utah datasets, respectively. All 3-dimensional stereotactic surface projection z score [18F]FDG maps were created in comparison to normal PET scans from 20 control cases whose amyloid PET scans were negative. Using the autopsy-derived z score maps, z score product indices (the individual z score map multiplied by the z scores of autopsy-confirmed cohorts) were generated for each subject, stratifying participants into probable LATE, probable LATE and AD (LATE+AD), and probable AD. Clinical and quantitative MRI volumetry data were compared across the groups using 1-way or Welch ANOVA and Fisher exact tests, depending on the assessed variables. Results: Of the 944 clinical cases, 13.0% were characterized as probable LATE (2.4% pure LATE and 10.6% LATE+AD) and 23.7% were characterized as probable AD without LATE. MRI volumetry revealed that the medial temporal lobe was most affected in pure LATE cases (P < 0.001), whereas the orbitofrontal gyrus and lateral temporal lobe were most vulnerable in mixed LATE+AD cases (P = 0.001; P < 0.001). Post hoc analysis identified the entorhinal cortex and amygdala as key regions for distinguishing mixed LATE+AD cases from pure LATE and pure AD cases, respectively (P = 0.05; P < 0.001). Subgroup analysis of the probable LATE+AD group demonstrated additive or synergistic effects of both pathologies, with three quarters of cases exhibiting concordant lateralized metabolic brain changes, predominantly left-sided, based on LATE and AD z score products (P < 0.001). A similar pattern of left-dominant brain atrophy was observed in MRI volumetry. Conclusion: Substantial numbers of our patients exhibited LATE features that were characterized objectively using scans from autopsy-proven cases. These LATE cases were associated with specific regional atrophy measured by quantitative MRI. Cases with LATE+AD copathologies demonstrated synergistic hemispheric involvement. Further investigations of such synergistic changes between LATE and AD are warranted.
{"title":"Copathologies of Limbic-Predominant Age-Related TDP-43 Encephalopathy and Alzheimer Disease: [18F]FDG PET Statistical Mapping and Quantitative MRI Volumetry.","authors":"Pei Ing Ngam,Yoshimi Anzai,Christine J Cliatt Brown,Nicholas Alonzo Frost,Michelle Keown Sorweid,Tanyaluck Thientunyakit,Satoshi Minoshima, ","doi":"10.2967/jnumed.125.270614","DOIUrl":"https://doi.org/10.2967/jnumed.125.270614","url":null,"abstract":"Limbic-predominant age-related transactive response DNA-binding protein 43 kDa encephalopathy (LATE) is emerging as a prevalent neurodegenerative disorder in aging populations, mimicking the clinical presentation of Alzheimer disease (AD). This study investigates in vivo [18F]FDG PET and MRI biomarkers in detecting probable LATE neuropathologic change. Methods: We retrospectively analyzed 944 [18F]FDG PET cases referred from cognitive disorder clinics in a tertiary care center. To characterize the LATE and AD findings objectively and quantitatively, we created 3-dimensional stereotactic surface projection PET templates for LATE neuropathologic change (n = 6) and AD neuropathologic change (n = 32) from autopsy-confirmed Alzheimer's Disease Neuroimaging Initiative and University of Utah datasets, respectively. All 3-dimensional stereotactic surface projection z score [18F]FDG maps were created in comparison to normal PET scans from 20 control cases whose amyloid PET scans were negative. Using the autopsy-derived z score maps, z score product indices (the individual z score map multiplied by the z scores of autopsy-confirmed cohorts) were generated for each subject, stratifying participants into probable LATE, probable LATE and AD (LATE+AD), and probable AD. Clinical and quantitative MRI volumetry data were compared across the groups using 1-way or Welch ANOVA and Fisher exact tests, depending on the assessed variables. Results: Of the 944 clinical cases, 13.0% were characterized as probable LATE (2.4% pure LATE and 10.6% LATE+AD) and 23.7% were characterized as probable AD without LATE. MRI volumetry revealed that the medial temporal lobe was most affected in pure LATE cases (P < 0.001), whereas the orbitofrontal gyrus and lateral temporal lobe were most vulnerable in mixed LATE+AD cases (P = 0.001; P < 0.001). Post hoc analysis identified the entorhinal cortex and amygdala as key regions for distinguishing mixed LATE+AD cases from pure LATE and pure AD cases, respectively (P = 0.05; P < 0.001). Subgroup analysis of the probable LATE+AD group demonstrated additive or synergistic effects of both pathologies, with three quarters of cases exhibiting concordant lateralized metabolic brain changes, predominantly left-sided, based on LATE and AD z score products (P < 0.001). A similar pattern of left-dominant brain atrophy was observed in MRI volumetry. Conclusion: Substantial numbers of our patients exhibited LATE features that were characterized objectively using scans from autopsy-proven cases. These LATE cases were associated with specific regional atrophy measured by quantitative MRI. Cases with LATE+AD copathologies demonstrated synergistic hemispheric involvement. Further investigations of such synergistic changes between LATE and AD are warranted.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021566","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 : 2026-01-16DOI: 10.2967/jnumed.125.271089
Seyed Ali Mirshahvalad,David Hodgson,John Kuruvilla,Patrick Veit-Haibach,Claudia Ortega,Ur Metser
Our rationale was to investigate the potential of interim [18F]FDG PET (iPET) in predicting large B-cell lymphoma (LBCL) patients' outcomes, including the end-of-treatment response, progression-free survival (PFS), and overall survival (OS). Methods: A systematic search was conducted on the 3 main medical literature databases until January 8, 2025. Published original articles that evaluated iPET for prognosticating LBCL patients and provided crude data for meta-analytic calculations were considered eligible. The hierarchic method was used to pool the random-effect model's end-of-treatment prediction performance measures of sensitivity, specificity, positive likelihood ratio (LR), and negative LR. The bivariate model was used to determine the corresponding 95% CI. Furthermore, PFS and OS were pooled across studies, including survival proportions and hazard ratios (HRs). All analyses were conducted using STATA 16 software. Results: The initial search resulted in 939 studies. After the full-text review, 44 studies were considered eligible. The pooled sensitivity and specificity of iPET for predicting end-of-treatment response were 0.78 (95% CI, 0.69-0.84) and 0.84 (95% CI, 0.78-0.88), respectively. On the basis of the pooled positive and negative LRs, iPET was not a reliable modality to exclude or confirm the end-of-treatment [18F]FDG PET results. The pooled PFS HR across all available datasets (n = 27) was 2.88 (95% CI, 2.35-3.52) for positive iPET (Deauville score [DS] 4-5). In datasets with HRs for positive iPET versus DS 5 alone, the pooled HRs were 2.36 (95% CI, 1.74-3.21) versus 5.59 (95% CI, 4.35-7.19). Furthermore, when datasets were limited to those with data on change in SUVmax versus DS 5 (n = 6), the pooled HRs were 3.41 (95% CI, 2.67-4.35) versus 5.59 (95% CI, 4.35-7.19), respectively. The pooled OS HR across all available datasets (n = 22) was 3.71 (95% CI, 2.93-4.69) for positive iPET. In datasets with HRs for positive iPET versus DS 5 alone (n = 5), the pooled HRs were 3.31 (95% CI, 2.09-5.24) versus 8.10 (95% CI, 6.04-10.85). Moreover, when datasets were limited to those with data on change in SUVmax versus DS 5 (n = 5), the pooled HRs were 4.54 (95% CI, 3.57-5.78) versus 8.10 (95% CI, 6.04-10.85). Conclusion: On the basis of our comprehensive systematic review and meta-analysis, DS 5 is a highly reliable predictor of unfavorable response to therapy on iPET. The utility of this threshold to escalate or modify therapy needs to be evaluated in future prospective trials.
{"title":"Prognostic Value of Interim [18F]FDG PET in Large B-Cell Lymphoma: A Systematic Review and Meta-analysis with a Particular Focus on Interim Deauville Score 5 Disease.","authors":"Seyed Ali Mirshahvalad,David Hodgson,John Kuruvilla,Patrick Veit-Haibach,Claudia Ortega,Ur Metser","doi":"10.2967/jnumed.125.271089","DOIUrl":"https://doi.org/10.2967/jnumed.125.271089","url":null,"abstract":"Our rationale was to investigate the potential of interim [18F]FDG PET (iPET) in predicting large B-cell lymphoma (LBCL) patients' outcomes, including the end-of-treatment response, progression-free survival (PFS), and overall survival (OS). Methods: A systematic search was conducted on the 3 main medical literature databases until January 8, 2025. Published original articles that evaluated iPET for prognosticating LBCL patients and provided crude data for meta-analytic calculations were considered eligible. The hierarchic method was used to pool the random-effect model's end-of-treatment prediction performance measures of sensitivity, specificity, positive likelihood ratio (LR), and negative LR. The bivariate model was used to determine the corresponding 95% CI. Furthermore, PFS and OS were pooled across studies, including survival proportions and hazard ratios (HRs). All analyses were conducted using STATA 16 software. Results: The initial search resulted in 939 studies. After the full-text review, 44 studies were considered eligible. The pooled sensitivity and specificity of iPET for predicting end-of-treatment response were 0.78 (95% CI, 0.69-0.84) and 0.84 (95% CI, 0.78-0.88), respectively. On the basis of the pooled positive and negative LRs, iPET was not a reliable modality to exclude or confirm the end-of-treatment [18F]FDG PET results. The pooled PFS HR across all available datasets (n = 27) was 2.88 (95% CI, 2.35-3.52) for positive iPET (Deauville score [DS] 4-5). In datasets with HRs for positive iPET versus DS 5 alone, the pooled HRs were 2.36 (95% CI, 1.74-3.21) versus 5.59 (95% CI, 4.35-7.19). Furthermore, when datasets were limited to those with data on change in SUVmax versus DS 5 (n = 6), the pooled HRs were 3.41 (95% CI, 2.67-4.35) versus 5.59 (95% CI, 4.35-7.19), respectively. The pooled OS HR across all available datasets (n = 22) was 3.71 (95% CI, 2.93-4.69) for positive iPET. In datasets with HRs for positive iPET versus DS 5 alone (n = 5), the pooled HRs were 3.31 (95% CI, 2.09-5.24) versus 8.10 (95% CI, 6.04-10.85). Moreover, when datasets were limited to those with data on change in SUVmax versus DS 5 (n = 5), the pooled HRs were 4.54 (95% CI, 3.57-5.78) versus 8.10 (95% CI, 6.04-10.85). Conclusion: On the basis of our comprehensive systematic review and meta-analysis, DS 5 is a highly reliable predictor of unfavorable response to therapy on iPET. The utility of this threshold to escalate or modify therapy needs to be evaluated in future prospective trials.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986391","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}
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