A C Berrens, K Pirkovets, S Azargoshasb, L J Slof, B A Cakal, P J van Leeuwen, E M K Wit, M Sinaasappel, T Wendler, H G van der Poel, M N van Oosterom, F W B van Leeuwen
{"title":"Redefining robotic image-guidance - tomographic visualization of lesions during prostate cancer surgery via gantry-free robotic SPECT.","authors":"A C Berrens, K Pirkovets, S Azargoshasb, L J Slof, B A Cakal, P J van Leeuwen, E M K Wit, M Sinaasappel, T Wendler, H G van der Poel, M N van Oosterom, F W B van Leeuwen","doi":"10.1007/s00259-026-07987-z","DOIUrl":"10.1007/s00259-026-07987-z","url":null,"abstract":"<p><strong>Purpose: </strong>The introduction of the drop-in gamma probe has advanced intraoperative molecular imaging during prostate cancer surgery. We have been able to convert the sensor's numeric readout to tomographic images, so-called robotic-SPECT (<sub>Robo</sub>SPECT) and investigate how this is impacted by radiopharmaceutical avidities and drop-in scan metrics.</p><p><strong>Methods: </strong>The gamma sensor readout was registered with its 3D position and orientation, allowing a custom reconstruction algorithm to generate <sub>Robo</sub>SPECT images. Evaluations occurred in 21 patients; 10 sentinel node procedures (SN; primary prostate cancer) and 11 PSMA-radioguided surgery (recurrent prostate cancer). <sub>Robo</sub>SPECT findings were related to respective pre- and intra-operative controls, including preoperative PSMA-PET/CT and/or SPECT/CT images and fluorescence detection (SN only).</p><p><strong>Results: </strong><sub>Robo</sub>SPECT proved to be safe and applicable in a range of conditions. In the SN-group, 26 SN-SPECT/CT lesions were successfully identified with SN-<sub>Robo</sub>SPECT (100%); 3 were tumor positive (sensitivity 100%). Only 73% of SNs were surgically visible with fluorescence imaging. For the PSMA guided group, the 14 lesions identified on PSMA-PET/CT were all visualized with PSMA-<sub>Robo</sub>SPECT (100%); 18 specimens were tumor positive (sensitivity 78% for both PSMA-PET/CT and PSMA-<sub>Robo</sub>SPECT). Preoperative PSMA-SPECT/CT only identified 4 PSMA-lesions (29%). No false positives were seen for <sub>robo</sub>SPECT and all final resection margins were clean. At 6-months 0% of the SN-patients and 20% of PSMA-patients showed biochemical recurrence.</p><p><strong>Conclusion: </strong><sub>Robo</sub>SPECT provides 3D context that extends the utility of drop-in gamma tracing and assists the alignment between pre- and intra-operative target perception. Here SN-<sub>Robo</sub>SPECT clearly outperformed fluorescence SN imaging and PSMA-<sub>Robo</sub>SPECT outperformed preoperative PSMA-SPECT/CT imaging.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"6858-6869"},"PeriodicalIF":7.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mads Ryø Jochumsen, Lise Medrud, André H Dias, Mette Abildgaard Pedersen, Christina Stilling, Kirsten Bouchelouche, Peter Iversen, Joan Fledelius, Lars Poulsen Tolbod, Louise Forsmann Grønnemark, Stefan Vind-Kezunovic, Morten Heebøll Andersen, Kasper Drimer Berg
{"title":"Prospective evaluation of the PRIMARY score using [<sup>18</sup>F]PSMA-1007 PET/MRI in second-line prostate biopsies after negative MRI.","authors":"Mads Ryø Jochumsen, Lise Medrud, André H Dias, Mette Abildgaard Pedersen, Christina Stilling, Kirsten Bouchelouche, Peter Iversen, Joan Fledelius, Lars Poulsen Tolbod, Louise Forsmann Grønnemark, Stefan Vind-Kezunovic, Morten Heebøll Andersen, Kasper Drimer Berg","doi":"10.1007/s00259-026-08070-3","DOIUrl":"10.1007/s00259-026-08070-3","url":null,"abstract":"<p><strong>Purpose: </strong>PSMA PET has been proposed for guiding targeted prostate biopsies. As the rate of clinically significant prostate cancer (csPCa) is positively correlated with PSA density (PSAd), a potential application for PSMA-guided biopsies may be men with negative MRI-first (PI-RADS-1-2) but increased PSAd. The PRIMARY scoring system, using the intraprostatic PSMA-pattern was developed and tested using [<sup>68</sup>Ga]Ga-PSMA-11 and proposed to be universal across PSMA-ligands, however no data on [<sup>18</sup>F]PSMA-1007 for biopsy guidance exists. Thus, the aim of this study was to evaluate the PRIMARY score for prostate biopsy guidance using [<sup>18</sup>F]PSMA-1007 in a prospective clinical setup.</p><p><strong>Methods: </strong>91 patients were prospectively enrolled for [<sup>18</sup>F]PSMA-1007 PET/MRI, 86 of these for biopsy guidance after negative MRI or non-csPCa biopsies from PI-RADS 3-5 lesions and persistent suspicion of csPCa. Transperineal MRI/ultrasound fusion target biopsies were performed predominantly from PRIMARY 3-5 lesions. Nine patients with PRIMARY 1-2 did not undergo target biopsies. CsPCa was defined as ISUP grade ≥ 2.</p><p><strong>Results: </strong>In a per patient analysis, 23.3% (20/86) were diagnosed with csPCa. In line with previous studies, the rate of csPCa increased with higher PRIMARY score in a per lesion analysis, constituting 0% (0/1), 0% (0/8), 7.2% (7/97), 60% (15/25), and 60% (6/10) for PRIMARY 1, 2, 3, 4, and 5 lesions, respectively. The 7.2% PRIMARY-3 lesions containing csPCa exhibited common characteristics such as anterior location or lack of well-defined separation from the peripheral zone.</p><p><strong>Conclusion: </strong>We evaluated the PRIMARY score for use with [¹⁸F]PSMA-1007 and identified benign features and potential \"red flags\" for PRIMARY-3 lesions. We found csPCa in 23.3% of patients with negative MRI or non-csPCa biopsies from PI-RADS 3-5 lesions and persistent suspicion of csPCa.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"7299-7312"},"PeriodicalIF":7.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jianhang Zhou, Robert J H Miller, Aakash Shanbhag, Aditya Killekar, Donghee Han, Krishna K Patel, Konrad Pieszko, Jirong Yi, Meghana Kiran Urs, Giselle Ramirez, Mark Lemley, Paul B Kavanagh, Joanna X Liang, Assiata Kamagate, Valerie Builoff, Andrew J Einstein, Attila Feher, Edward J Miller, Albert J Sinusas, Terrence D Ruddy, Stacey Knight, Viet T Le, Steve Mason, Panithaya Chareonthaitawee, Samuel Wopperer, Erick Alexanderson, Isabel Carvajal-Juarez, Thomas L Rosamond, Leandro Slipczuk, Mark I Travin, René R S Packard, Wanda Acampa, Mouaz Al-Mallah, Robert A deKemp, Ronny R Buechel, Daniel S Berman, Damini Dey, Marcelo F Di Carli, Piotr J Slomka
{"title":"Hidden risk in normal myocardial perfusion scans: AI-detected proximal coronary calcium on CT attenuation maps improves prognosis.","authors":"Jianhang Zhou, Robert J H Miller, Aakash Shanbhag, Aditya Killekar, Donghee Han, Krishna K Patel, Konrad Pieszko, Jirong Yi, Meghana Kiran Urs, Giselle Ramirez, Mark Lemley, Paul B Kavanagh, Joanna X Liang, Assiata Kamagate, Valerie Builoff, Andrew J Einstein, Attila Feher, Edward J Miller, Albert J Sinusas, Terrence D Ruddy, Stacey Knight, Viet T Le, Steve Mason, Panithaya Chareonthaitawee, Samuel Wopperer, Erick Alexanderson, Isabel Carvajal-Juarez, Thomas L Rosamond, Leandro Slipczuk, Mark I Travin, René R S Packard, Wanda Acampa, Mouaz Al-Mallah, Robert A deKemp, Ronny R Buechel, Daniel S Berman, Damini Dey, Marcelo F Di Carli, Piotr J Slomka","doi":"10.1007/s00259-026-08084-x","DOIUrl":"10.1007/s00259-026-08084-x","url":null,"abstract":"<p><strong>Purpose: </strong>Spatial distribution of coronary artery calcium (CAC) may provide additional prognostic value in patients undergoing SPECT and PET myocardial perfusion imaging (MPI). We aimed to automatically identify CAC in proximal segments from attenuation correction CT (CTAC) scans using artificial intelligence (AI) and to evaluate prognostic significance in two large international multicenter registries.</p><p><strong>Methods: </strong>From hybrid MPI/CT imaging (N = 43,099) across 15 sites, we included 4,552 most relevant patients with (1) no prior coronary artery disease; (2) AI-derived mild CAC scores (1-99); and (3) normal perfusion (stress total perfusion deficit < 5%). The independent associations between AI-identified proximal CAC and major adverse cardiovascular events (MACE) and all-cause mortality (ACM) were evaluated using multivariable Cox regression, likelihood ratio test (LRT), and continuous net reclassification index (NRI).</p><p><strong>Results: </strong>Among the patients with mild CAC and normal perfusion (mean age 65 ± 12 years, 51% male), 1,730 (38%) had proximal CAC. Over 3.6 (inter-quartile interval 2.1, 5.2) years follow-up, 599 (13%) and 444 (10%) patients had MACE or ACM, respectively. Proximal CAC was associated with an increased risk of MACE (adjusted hazard ratio [HR] 1.24, 95% CI 1.03-1.48, P = 0.02) and ACM (adjusted HR 1.25, 95% CI 1.01-1.53, P = 0.04) after the adjustment of CAC score and density, clinical risk factors, and perfusion deficit. Proximal CAC improved the risk stratification of MACE (LRT P = 0.02; NRI 12%) and ACM (LRT P = 0.04; NRI 12%).</p><p><strong>Conclusion: </strong>In patients with mild CAC and normal myocardial perfusion, AI-based proximal CAC detection identified a subgroup at increased risk of adverse outcomes. Automated identification of proximal CAC may provide incremental prognostic information beyond perfusion findings and CAC scoring and could improve risk stratification in patients who might otherwise be considered low risk.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"7610-7620"},"PeriodicalIF":7.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13492496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoyun Luo, Chentao Jin, Yuanjie Chen, Peili Cen, Rui Zhou, Jing Wang, Han Jiang, Mei Tian, Hong Zhang, Yan Zhong
{"title":"A novel mWGA-TYR PET reporter gene system for in vivo visualization of whole brain-level neural circuit.","authors":"Xiaoyun Luo, Chentao Jin, Yuanjie Chen, Peili Cen, Rui Zhou, Jing Wang, Han Jiang, Mei Tian, Hong Zhang, Yan Zhong","doi":"10.1007/s00259-026-08104-w","DOIUrl":"10.1007/s00259-026-08104-w","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to develop a novel PET reporter gene imaging system based on modified wheat germ agglutinin (mWGA) and tyrosinase (TYR) for tracing trans‑monosynaptic neural circuit in vivo.</p><p><strong>Methods: </strong>Mouse neural stem cells NE4C were engineered via lentiviral transduction to express mWGA-TYR and GFP. TYR expression was confirmed by western blot and RT-qPCR. Melanin production was assessed using Masson-Fontana staining, gamma counting, and <sup>18</sup>F-FPABZA PET imaging. In vitro trans-synaptic transfer was evaluated by co‑culturing transduced NE4C cells with naive cells. To validate the system in the normal brain, an rAAV vector encoding mWGA-TYR was delivered into the right sensorimotor cortex. In vivo melanin transport along neural circuits was traced by <sup>18</sup>F-FPABZA PET imaging and confirmed by ex vivo immunofluorescent staining. Finally, the system was tested in an ischemic stroke model following NE4C transplantation.</p><p><strong>Results: </strong>Lentiviral transduction of NE4C cells led to successful expression of mWGA, TYR and GFP. Masson‑Fontana staining confirmed melanin production, while gamma counting and <sup>18</sup>F‑FPABZA PET imaging showed significantly higher radiotracer uptake in TYR‑expressing cells in vitro. In co‑culture experiments, mWGA‑TYR underwent trans‑synaptic transfer from transduced to naive NE4C cells. Following rAAV injection into the right sensorimotor cortex, <sup>18</sup>F‑FPABZA PET signals were detected in multiple brain regions, with ex vivo immunofluorescence corroborated these connectivity patterns. In the ischemic stroke model with NE4C transplantation, elevated PET signals were observed at both the transplantation site and distal sites two weeks after transplantation, which was further validated by ex vivo analyses. Furthermore, HSV‑1‑H129 tracing confirmed the anterograde trans‑monosynaptic capability of mWGA‑TYR system.</p><p><strong>Conclusion: </strong>This study developed a novel mWGA-TYR PET reporter gene system for non-invasive in vivo tracing of anterograde trans-monosynaptic neural circuits. This system can be extended to monitor graft-host neural circuit connections in stem cell therapy for ischemic stroke.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"7527-7537"},"PeriodicalIF":7.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148619055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rhinocerebral mucormycosis: a potential source of false-positive uptake on [<sup>18</sup>F]FET PET/MR leading to diagnostic ambiguity.","authors":"Rangat Bagasariya, Keerti Sitani, Aekta Shah, Sandip Basu","doi":"10.1007/s00259-026-07914-2","DOIUrl":"10.1007/s00259-026-07914-2","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"6717-6719"},"PeriodicalIF":7.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147987231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinyu Liu, Li Sun, Jialiang Lei, Liyan Bai, Haoyao Guo, Yichong Fang, Jianping Zhang, Chunjuan Jiang, Xiaoping Xu, Shaoli Song
{"title":"Translation of a novel EphA2-targeted PET tracer from preclinical models to first-in-human studies in pancreatic cancer.","authors":"Xinyu Liu, Li Sun, Jialiang Lei, Liyan Bai, Haoyao Guo, Yichong Fang, Jianping Zhang, Chunjuan Jiang, Xiaoping Xu, Shaoli Song","doi":"10.1007/s00259-026-07966-4","DOIUrl":"10.1007/s00259-026-07966-4","url":null,"abstract":"<p><strong>Purpose: </strong>Ephrin type-A receptor 2 (EphA2) is a promising target in pancreatic ductal adenocarcinoma (PDAC). However, the clinical potential of targeting EphA2 requires further imaging evaluation. This study developed and preliminarily evaluated a novel <sup>68</sup>Ga-labeled radiotracer for PET imaging of EphA2 expression in PDAC patients.</p><p><strong>Methods: </strong><sup>68</sup>Ga-FZEAR-1, <sup>68</sup>Ga-FZEAR-2, and <sup>68</sup>Ga-FZEAR-3 were synthesized, and their stability, affinity, pharmacokinetics were evaluated in vitro and in vivo. Further biological evaluation was performed in EphA2-positive and EphA2-negative tumor xenografts. A pilot first-in-human PET/CT study of the lead candidate, <sup>68</sup>Ga-FZEAR-2, was subsequently conducted in two PDAC patients.</p><p><strong>Results: </strong>The three <sup>68</sup>Ga-radiotracers were synthesized with high radiochemical purity (> 99%) and demonstrated high stability and nanomolar affinity for EphA2. Cellular uptake was consistent with EphA2 expression and blocking assays confirmed specificity. In vivo, all tracers exhibited high tumor accumulation with low off-target uptake. <sup>68</sup>Ga-FZEAR-2 showed favorable tumor-targeting ability, pharmacokinetics, and safety profile. In the pilot clinical study (n = 2), <sup>68</sup>Ga-FZEAR-2 PET/CT visualized primary and metastatic lesions clearly without adverse effects. Immunohistochemical analysis confirmed EphA2 expression in lesions exhibiting high tracer uptake.</p><p><strong>Conclusion: </strong>A series of <sup>68</sup>Ga-labeled tracers for EphA2 imaging was successfully developed and evaluated. The lead candidate, <sup>68</sup>Ga-FZEAR-2, showed promising targeting specificity and favorable pharmacokinetics. A pilot study indicated that <sup>68</sup>Ga-FZEAR-2 provided preliminary evidence of noninvasive visualization of EphA2 expression in PDAC patients, thereby suggesting its potential as a tool for precision diagnosis in PDAC.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"6823-6836"},"PeriodicalIF":7.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karine Madsen, Kirsten Korsholm, Flemming Littrup Andersen, Thomas Lund Andersen
{"title":"Dynamic LAFOV PET/CT imaging of [<sup>18</sup>F]FDG uptake in the human fetus.","authors":"Karine Madsen, Kirsten Korsholm, Flemming Littrup Andersen, Thomas Lund Andersen","doi":"10.1007/s00259-026-08192-8","DOIUrl":"https://doi.org/10.1007/s00259-026-08192-8","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jasper Smit, Frank J Borm, Nienke R Gerards, Sanne E Wiegers, Daniel Holden, David Leung, Diederik J Grootendorst, Bert Windhorst, Nabeel Nabulsi, Zhengxin Cai, Yiyun Huang, Richard E Carson, Scott Gettinger, Egbert F Smit, Ronald Boellaard, Adrianus J de Langen
{"title":"PD-L1 PET/CT imaging with <sup>18</sup>F-BMS-986,229 and <sup>18</sup>F-BMS-986,192 in patients with advanced-stage non-small cell lung cancer.","authors":"Jasper Smit, Frank J Borm, Nienke R Gerards, Sanne E Wiegers, Daniel Holden, David Leung, Diederik J Grootendorst, Bert Windhorst, Nabeel Nabulsi, Zhengxin Cai, Yiyun Huang, Richard E Carson, Scott Gettinger, Egbert F Smit, Ronald Boellaard, Adrianus J de Langen","doi":"10.1007/s00259-026-08188-4","DOIUrl":"https://doi.org/10.1007/s00259-026-08188-4","url":null,"abstract":"<p><strong>Purpose: </strong>Predicting response to checkpoint inhibitors in non-small cell lung cancer (NSCLC) remains challenging. In addition to programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC), PD-L1 imaging could improve response prediction. This study evaluated a novel PD-L1 PET tracer, <sup>18</sup>F-BMS-986,229, and compared its performance to <sup>18</sup>F-BMS-986,192, which shares the same target.</p><p><strong>Methods: </strong>Stage IV NSCLC patients were scheduled for baseline PET/CT scans with both tracers. Tracer uptake was quantified using SUVpeak and SUVmean. Imaging findings were correlated with PD-L1 expression from tumor biopsies and clinical outcomes, including best overall response and overall survival.</p><p><strong>Results: </strong><sup>18</sup>F-BMS-986,192 and <sup>18</sup>F-BMS-986,229 performed equally with respect to tumor tracer uptake. Mean SUVpeak was 2.75 (SD 1.53) vs. 2.68 (SD 1.78), p = 0.780. Tumor tracer uptake did not correlate with PD-L1 IHC, mean SUVpeak in the PD-L1 tps < 50% group was 3.77 vs. 3.54 in the PD-L1 ≥ 50% group (p = 0.8175). Explorative analysis of the association between tumor tracer uptake and OS revealed that a low SUVpeak excluded a long OS, whereas a higher SUVpeak did not discriminate between patients with a short or long OS.</p><p><strong>Conclusion: </strong><sup>18</sup>F-BMS-986,229 and <sup>18</sup>F-BMS-986,192 performed equally with respect to tumor uptake. In this small cohort, baseline PD-L1 tracer uptake did not correlate with PD-L1 IHC. Low tumor tracer uptake may be associated with shorter overall survival, warranting further investigation.</p><p><strong>Clinical trial registration: </strong>NCT03001882, https//clinicaltrials.gov/study/NCT03001882.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Borna Roohani, Ayla Vaughn Embs, Robin Kumar, Supum Lee, Samantha R. Katz, Chloe La Prairie, Dajah Nash, Mann Dangarwala, Harriet M. Kluger, Daryl E. Klein, Ping Zhang, Benjamin M. Larimer, Bryce Nelson, Bernadette Marquez-Nostra
{"title":"A FABulous approach to image human macrophages","authors":"Borna Roohani, Ayla Vaughn Embs, Robin Kumar, Supum Lee, Samantha R. Katz, Chloe La Prairie, Dajah Nash, Mann Dangarwala, Harriet M. Kluger, Daryl E. Klein, Ping Zhang, Benjamin M. Larimer, Bryce Nelson, Bernadette Marquez-Nostra","doi":"10.1007/s00259-026-08180-y","DOIUrl":"https://doi.org/10.1007/s00259-026-08180-y","url":null,"abstract":"Rationale Imaging tumor-associated macrophages (TAMs) may reflect prognosis, therapeutic response and radiotheranostic potential. We report the discovery and development of a synthetic human Fab as the first immunoPET tracer targeting human CD68 (huCD68), the gold standard histopathological biomarker of pan-macrophages. Methods Phage display was used to identify novel huCD68-specific Fabs. The lead Fab for immunoPET development was chosen based on expression yield and stability. Fab was conjugated to p-SCN-Bn-DFO and radiolabeled with <jats:sup>89</jats:sup> Zr, yielding [ <jats:sup>89</jats:sup> Zr]Zr-DFO-Fab. Stability and specific binding of the tracer to THP-1 macrophages were assessed in vitro. The specificity of the tracer in vivo was characterized by PET imaging of two different animal models: 1) BALB/c mice bearing huCD68 antigen- or irrelevant protein-plugs, and 2) tumor xenografted NSG mice intratumorally injected with either THP-1 macrophages or THP-1 undifferentiated cells. Finally, tumors were subjected to immunofluorescence (IF) staining of huCD68 and correlated with PET standardized uptake values (SUV). Results Four novel huCD68-specific Fabs were identified. Fab8 was chosen as the lead based on high expression yield, purity, and stability. In vivo, [ <jats:sup>89</jats:sup> Zr]Zr-DFO-Fab8 uptake was significantly higher in huCD68 antigen-plugs than in irrelevant protein-plugs at 1- and 4-h post-injection (p.i.). Tracer uptake in THP-1 macrophage tumors was also significantly higher than in THP-1 undifferentiated tumors at 1- and 6-h p.i.. IF of tumors confirmed higher density of huCD68 in those implanted with THP-1 macrophages than those with THP-1 undifferentiated cells. CD68 expression highly correlated with immunoPET SUV. Conclusion [ <jats:sup>89</jats:sup> Zr]Zr-DFO-Fab8 binds specifically to huCD68, supporting the feasibility of direct PET-to-histopathogical correlation of total TAM burden.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"40 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesco Mattana, Stefano Luzzago, Valentino Dragonetti, Veeru Kasivisvanathan, Sinead Conlon, Paolo Castellucci, Andrea Farolfi, Marcin Miszczyk, Tomasz Techmański, Pawel Rajwa, Shahrokh F Shariat, Fabio Zattoni, Giuseppe Reitano, Alberto Briganti, Francesco Montorsi, Samuele Frassoni, Vincenzo Bagnardi, Giorgio Gandaglia, Francesco Ceci
{"title":"Stage migration in prostate cancer: the role of PSMA-PET in identifying oligometastatic disease","authors":"Francesco Mattana, Stefano Luzzago, Valentino Dragonetti, Veeru Kasivisvanathan, Sinead Conlon, Paolo Castellucci, Andrea Farolfi, Marcin Miszczyk, Tomasz Techmański, Pawel Rajwa, Shahrokh F Shariat, Fabio Zattoni, Giuseppe Reitano, Alberto Briganti, Francesco Montorsi, Samuele Frassoni, Vincenzo Bagnardi, Giorgio Gandaglia, Francesco Ceci","doi":"10.1007/s00259-026-08166-w","DOIUrl":"https://doi.org/10.1007/s00259-026-08166-w","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"49 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}