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

{"title":"Dosimetry of [¹⁷⁷Lu]Lu-PSMA-Targeted Radiopharmaceutical Therapies in Patients with Prostate Cancer: A Comparative Systematic Review and Metaanalysis.","authors":"Zachary Ells, Tristan R Grogan, Johannes Czernin, Magnus Dahlbom, Jeremie Calais","doi":"10.2967/jnumed.124.267452","DOIUrl":"10.2967/jnumed.124.267452","url":null,"abstract":"<p><p>Novel theranostic approaches using radiopharmaceuticals targeting prostate-specific membrane antigen (PSMA) have emerged for treating metastatic castration-resistant prostate cancer. The physical properties and commercial availability of ¹⁷⁷Lu make it one of the most used radionuclides for radiopharmaceutical therapy (RPT). In this literature review, we aimed at comparing the dosimetry of the most used [¹⁷⁷Lu]Lu-PSMA RPT compounds. <b>Methods:</b> This was a systematic review and metaanalysis of [¹⁷⁷Lu]Lu-PSMA RPT (617, I&T, and J591) dosimetry in patients with prostate cancer. Absorbed doses in Gy/GBq for each organ at risk (kidney, parotid and submandibular glands, bone marrow, liver, and lacrimal glands) and for tumor lesions (bone and nonbone lesions) were extracted from included articles. These were used to estimate the pooled average absorbed dose of each agent in Gy/GBq and in Gy/cycle, normalized to the injected activity (per cycle) used in the VISION (7.4 GBq), SPLASH (6.8 GBq), and PROSTACT trials (5.8 GBq). <b>Results:</b> Twenty-nine published articles comprising 535 patients were included in the metaanalysis. The pooled doses (weighted average across studies) of [¹⁷⁷Lu]Lu-PSMA-617 and [¹⁷⁷Lu]Lu-PSMA-I&T were 4.04 Gy/GBq (17 studies, 297 patients) and 4.70 Gy/GBq (10 studies, 153 patients) for the kidney (<i>P</i> = 0.10), 5.85 Gy/GBq (14 studies, 216 patients) and 2.62 Gy/GBq (5 studies, 86 patients) for the parotids (<i>P</i> < 0.01), 5.15 Gy/GBq (5 studies, 81 patients) and 4.35 Gy/GBq (1 study, 18 patients) for the submandibular glands (<i>P</i> = 0.56), 11.03 Gy/GBq (6 studies, 121 patients) and 19.23 Gy/GBq (3 studies, 53 patients) for the lacrimal glands (<i>P</i> = 0.20), 0.24 Gy/GBq (12 studies, 183 patients) and 0.19 Gy/GBq (4 studies, 68 patients) for the bone marrow (<i>P</i> = 0.31), and 1.11 Gy/GBq (9 studies, 154 patients) and 0.56 Gy/GBq (4 studies, 56 patients) for the liver (<i>P</i> = 0.05), respectively. Average tumor doses tended to be higher for [¹⁷⁷Lu]Lu-PSMA-617 than for [¹⁷⁷Lu]Lu-PSMA-I&T in soft tissue tumor lesions (4.19 vs. 2.94 Gy/GBq; <i>P</i> = 0.26). Dosimetry data of [¹⁷⁷Lu]Lu-J591 were limited to one published study of 35 patients with reported absorbed doses of 1.41, 0.32, and 2.10 Gy/GBq to the kidney, bone marrow, and liver, respectively. <b>Conclusion:</b> In this metaanalysis, there was no significant difference in absorbed dose between [¹⁷⁷Lu]Lu-PSMA-I&T and [¹⁷⁷Lu]Lu-PSMA-617. There was a possible trend toward a higher kidney dose with [¹⁷⁷Lu]Lu-PSMA-I&T and a higher tumor lesion dose with [¹⁷⁷Lu]Lu-PSMA-617. It remains unknown whether this finding has any clinical impact. The dosimetry methodologies were strikingly heterogeneous among studies, emphasizing the need for standardization.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>h</i>HEPATO-Cy5, a Bimodal Tracer for Image-Guided Hepatobiliary Surgery.","authors":"Daphne D D Rietbergen, Tessa Buckle, Leon J Slof, Maarten P van Meerbeek, Clarize M de Korne, Mick M Welling, Matthias N van Oosterom, Kevin Bauwens, Meta Roestenberg, Julia Kloetzl, Fijs W B van Leeuwen","doi":"10.2967/jnumed.123.266715","DOIUrl":"10.2967/jnumed.123.266715","url":null,"abstract":"<p><p>Liver cancer is a leading cause of cancer deaths worldwide. Surgical resection of superficial hepatic lesions is increasingly guided by the disrupted bile excretion of the fluorescent dye indocyanine green (ICG). To extend this approach to deeper lesions, a dedicated bimodal tracer that facilitates both fluorescence guidance and radioguidance was developed. <b>Methods:</b> A tracer comprising a methylated cyanine-5 (Cy5) fluorescent dye and a mercaptoacetyltriserine chelate (<i>h</i>HEPATO-Cy5) was synthesized and characterized. Cellular uptake and excretion were evaluated in hepatocyte cultures (2-dimensional culture and in vitro lesion model), using a fluorescent bile salt, MitoTracker dye, and methylated Cy5 as a control. After radiolabeling, the pharmacokinetics of ^99mTc-<i>h</i>HEPATO-Cy5 were assessed in mice over 24 h (percentage injected dose and percentage injected dose per gram of tissue, SPECT/CT imaging and fluorescence imaging). The ability to provide real-time fluorescence guidance during robot-assisted hepatobiliary surgery was evaluated in a porcine model using ICG as a reference. <b>Results:</b> The unique molecular signature of <i>h</i>HEPATO-Cy5 promotes hepatobiliary excretion. In vitro studies on hepatocytes showed that where methylated Cy5 remained internalized, <i>h</i>HEPATO-Cy5 showed fast clearance (10 min) similar to that of fluorescent bile salt. In vivo use of ^99mTc-<i>h</i>HEPATO-Cy5 in mice revealed liver accumulation and rapid biliary clearance. The effectiveness of bile clearance was best exemplified by the 2-orders-of-magnitude reduction in count rate for the gallbladder (<i>P</i> = 0.008) over time. During hepatobiliary surgery in a porcine model, <i>h</i>HEPATO-Cy5 enabled fluorescence-based lesion identification comparable to that of ICG. <b>Conclusion:</b> The bimodal ^99mTc-<i>h</i>HEPATO-Cy5 provides an effective means to identify liver lesions. Uniquely, it helps overcome the shortcomings of fluorescence-only approaches by allowing for an extension to in-depth radioguidance.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RadShap: An Explanation Tool for Highlighting the Contributions of Multiple Regions of Interest to the Prediction of Radiomic Models.","authors":"Nicolas Captier, Fanny Orlhac, Narinée Hovhannisyan-Baghdasarian, Marie Luporsi, Nicolas Girard, Irène Buvat","doi":"10.2967/jnumed.124.267434","DOIUrl":"10.2967/jnumed.124.267434","url":null,"abstract":"<p><p>Explaining the decisions made by a radiomic model is of significant interest, as it can provide valuable insights into the information learned by complex models and foster trust in well-performing ones, thereby facilitating their clinical adoption. Promising radiomic approaches that aggregate information from multiple regions within an image currently lack suitable explanation tools that could identify the regions that most significantly influence their decisions. Here we present a model- and modality-agnostic tool (RadShap, https://github.com/ncaptier/radshap), based on Shapley values, that explains the predictions of multiregion radiomic models by highlighting the contribution of each individual region. <b>Methods:</b> The explanation tool leverages Shapley values to distribute the aggregative radiomic model's output among all the regions of interest of an image, highlighting their individual contribution. RadShap was validated using a retrospective cohort of 130 patients with advanced non-small cell lung cancer undergoing first-line immunotherapy. Their baseline PET scans were used to build 1,000 synthetic tasks to evaluate the degree of alignment between the tool's explanations and our data generation process. RadShap's potential was then illustrated through 2 real case studies by aggregating information from all segmented tumors: the prediction of the progression-free survival of the non-small cell lung cancer patients and the classification of the histologic tumor subtype. <b>Results:</b> RadShap demonstrated strong alignment with the ground truth, with a median frequency of 94% for consistently explained predictions in the synthetic tasks. In both real-case studies, the aggregative models yielded superior performance to the single-lesion models (average [±SD] time-dependent area under the receiver operating characteristic curve was 0.66 ± 0.02 for the aggregative survival model vs. 0.55 ± 0.04 for the primary tumor survival model). The tool's explanations provided relevant insights into the behavior of the aggregative models, highlighting that for the classification of the histologic subtype, the aggregative model used information beyond the biopsy site to correctly classify patients who were initially misclassified by a model focusing only on the biopsied tumor. <b>Conclusion:</b> RadShap aligned with ground truth explanations and provided valuable insights into radiomic models' behaviors. It is implemented as a user-friendly Python package with documentation and tutorials, facilitating its smooth integration into radiomic pipelines.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diverse Imaging Methods May Influence Long-Term Oncologic Outcomes in Oligorecurrent Prostate Cancer Patients Treated with Metastasis-Directed Therapy (the PRECISE-MDT Study).","authors":"Matteo Bauckneht, Francesco Lanfranchi, Domenico Albano, Luca Triggiani, Flavia Linguanti, Luca Urso, Rosario Mazzola, Alessio Rizzo, Elisa D'Angelo, Francesco Dondi, Eneida Mataj, Gloria Pedersoli, Elisabetta Maria Abenavoli, Luca Vaggelli, Beatrice Detti, Naima Ortolan, Antonio Malorgio, Alessia Guarneri, Federico Garrou, Matilde Fiorini, Serena Grimaldi, Pietro Ghedini, Giuseppe Carlo Iorio, Antonella Iudicello, Guido Rovera, Giuseppe Fornarini, Diego Bongiovanni, Michela Marcenaro, Filippo Maria Pazienza, Giorgia Timon, Matteo Salgarello, Manuela Racca, Mirco Bartolomei, Stefano Panareo, Umberto Ricardi, Francesco Bertagna, Filippo Alongi, Salvina Barra, Silvia Morbelli, Gianmario Sambuceti, Liliana Belgioia","doi":"10.2967/jnumed.124.267586","DOIUrl":"10.2967/jnumed.124.267586","url":null,"abstract":"<p><p>Metastasis-directed therapy (MDT) has been tested in clinical trials as a treatment option for oligorecurrent prostate cancer (PCa). However, there is an ongoing debate regarding the impact of using different imaging techniques interchangeably for defining lesions and guiding MDT within clinical trials. <b>Methods:</b> We retrospectively identified oligorecurrent PCa patients who had 5 or fewer nodal, bone, or visceral metastases detected by choline or prostate-specific membrane antigen (PSMA) PET/CT and who underwent MDT stereotactic body radiotherapy with or without systemic therapy in 8 tertiary-level cancer centers. Imaging-guided MDT was assessed as progression-free survival (PFS), time to systemic treatment change due to polymetastatic conversion (PFS2), and overall survival predictor. Propensity score matching was performed to account for clinical differences between groups. <b>Results:</b> Of 402 patients, 232 (57.7%) and 170 (42.3%) underwent MDT guided by [¹⁸F]fluorocholine and PSMA PET/CT, respectively. After propensity score matching, patients treated with PSMA PET/CT-guided MDT demonstrated longer PFS (hazard ratio [HR], 0.49 [95% CI, 0.36-0.67]; <i>P</i> < 0.0001), PFS2 (HR, 0.42 [95% CI, 0.28-0.63]; <i>P</i> < 0.0001), and overall survival (HR, 0.39 [95% CI, 0.15-0.99]; <i>P</i> < 0.05) than those treated with choline PET/CT-guided MDT. Additionally, we matched patients who underwent [⁶⁸Ga]Ga-PSMA-11 versus [¹⁸F]F-PSMA-1007 PET/CT, observing longer PFS and PFS2 in the former subgroup (PFS: HR, 0.51 [95% CI, 0.26-1.00]; <i>P</i> < 0.05; PFS2: HR, 0.24 [95% CI, 0.09-0.60]; <i>P</i> < 0.05). <b>Conclusion:</b> Diverse imaging methods may influence outcomes in oligorecurrent PCa patients undergoing MDT. However, prospective, head-to-head studies, ideally incorporating a randomized design, are necessary to provide definitive evidence and facilitate the practical application of these findings.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performing [¹⁸F]MFBG Long-Axial-Field-of-View PET/CT Without Sedation or General Anesthesia for Imaging of Children with Neuroblastoma.","authors":"Lise Borgwardt, Jesper Brok, Kim Francis Andersen, Jacob Madsen, Nicholas Gillings, Marie Øbro Fosbøl, Charlotte Lund Denholt, Ida Nymann Petersen, Louise Sørup Sørensen, Lotte Hahn Enevoldsen, Peter Sandor Oturai, Helle Hjort Johannesen, Liselotte Højgaard, Christina Schulze, Eunice Saxtoft, Flemming Andersen, Barbara Malene Fischer","doi":"10.2967/jnumed.123.267256","DOIUrl":"10.2967/jnumed.123.267256","url":null,"abstract":"<p><p>Meta-[¹²³I]iodobenzylguanidine ([¹²³I]MIBG) scintigraphy with SPECT/CT is the standard of care for diagnosing and monitoring neuroblastoma. Replacing [¹²³I]MIBG with the new PET tracer meta-[¹⁸F]fluorobenzylguanidine ([¹⁸F]MFBG) and further improving sensitivity and reducing noise in a new long-axial-field-of-view (LAFOV) PET/CT scanner enable increased image quality and a faster acquisition time, allowing examinations to be performed without sedation or general anesthesia (GA). Focusing on feasibility, we present our first experience with [¹⁸F]MFBG LAFOV PET/CT and compare it with [¹²³I]MIBG scintigraphy plus SPECT/CT for imaging in neuroblastoma in children. <b>Methods:</b> A pilot of our prospective, single-center study recruited children with neuroblastoma who were referred for [¹²³I]MIBG scintigraphy with SPECT/CT. Within 1 wk of [¹²³I]MIBG scintigraphy and SPECT/low-dose CT, [¹⁸F]MFBG LAFOV PET/ultra-low-dose CT was performed 1 h after injection (1.5-3 MBq/kg) without sedation or GA, in contrast to the 24-h postinjection interval needed for scanning with [¹²³I]MIBG, the 2- to 2.5-h acquisition time, and the GA often needed in children less than 6 y old. Based on the spirocyclic iodonium-ylide precursor, [¹⁸F]MFBG was produced in a fully automated good manufacturing practice-compliant procedure. We present the feasibility of the study. <b>Results:</b> In the first paired scans of the first 10 children included (5 at diagnosis, 2 during treatment, 2 during surveillance, and 1 at relapse), [¹⁸F]MFBG PET/CT scan showed a higher number of radiotracer-avid lesions in 80% of the cases and an equal number of lesions in 20% of the cases. The SIOPEN score was higher in 50% of the cases, and the Curie score was higher in 70% of the cases. In particular, intraspinal, retroperitoneal lymph node, and bone marrow involvement was diagnosed with much higher precision. None of the children (median age, 1.6 y; range, 0.1-7.9 y) had sedation or GA during the PET procedure, whereas 80% had GA during [¹²³I]MIBG scintigraphy with SPECT/CT. A PET acquisition time of only 2 min without motion artifacts was the data requirement of the 10-min acquisition time for reconstruction to provide a clinically useful image. <b>Conclusion:</b> This pilot study demonstrates the feasibility of performing [¹⁸F]MFBG LAFOV PET/CT for imaging of neuroblastoma. Further, an increased number of radiotracer-avid lesions, an increased SIOPEN score, and an increased Curie score were seen on [¹⁸F]MFBG LAFOV PET/CT compared with [¹²³I]MIBG scintigraphy with SPECT/CT, and GA and sedation was avoided in all patients. Thus, with a 1-d protocol, a significantly shorter scan time, a higher sensitivity, and the avoidance of GA and sedation, [¹⁸F]MFBG LAFOV PET/CT shows promise for future staging ","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of ⁶⁴Cu-, ⁵⁵Co-, and ⁶⁸Ga-Labeled Radiopharmaceuticals Targeting Neurotensin Receptor-1 for Theranostics: Adjusting In Vivo Distribution Using Multiamine Macrocycles.","authors":"German O Fonseca Cabrera, Xinrui Ma, Wilson Lin, Tao Zhang, Weiling Zhao, Liqin Pan, Xiaomei Li, Todd E Barnhart, Eduardo Aluicio-Sarduy, Huaifu Deng, Xuedan Wu, Kadalipura P Rakesh, Zibo Li, Jonathan W Engle, Zhanhong Wu","doi":"10.2967/jnumed.124.267469","DOIUrl":"10.2967/jnumed.124.267469","url":null,"abstract":"<p><p>The development of theranostic radiotracers relies on their binding to specific molecular markers of a particular disease and the use of corresponding radiopharmaceutical pairs thereafter. This study reports the use of multiamine macrocyclic moieties (MAs), as linkers or chelators, in tracers targeting the neurotensin receptor-1 (NTSR-1). The goal is to achieve elevated tumor uptake, minimal background interference, and prolonged tumor retention in NTSR-1-positive tumors. <b>Methods:</b> We synthesized a series of neurotensin antagonists bearing MA linkers and metal chelators. The MA unit is hypothesized to establish a strong interaction with the cell membrane, and the addition of a second chelator may enhance water solubility, consequently reducing liver uptake. Small-animal PET/CT imaging of [⁶⁴Cu]Cu-DOTA-SR-3MA, [⁶⁴Cu]Cu-NT-CB-NOTA, [⁶⁸Ga]Ga-NT-CB-NOTA, [⁶⁴Cu]Cu-NT-CB-DOTA, and [⁶⁴Cu]Cu-NT-Sarcage was acquired at 1, 4, 24, and 48 h after injection using H1299 tumor models. [⁵⁵Co]Co-NT-CB-NOTA was also tested in HT29 (high NTSR-1 expression) and Caco2 (low NTSR-1 expression) colorectal adenocarcinoma tumor models. Saturation binding assay and internalization of [⁵⁵Co]Co-NT-CB-NOTA were used to test tracer specificity and internalization in HT29 cells. <b>Results:</b> In vivo PET imaging with [⁶⁴Cu]Cu-NT-CB-NOTA, [⁶⁸Ga]Ga-NT-CB-NOTA, and [⁵⁵Co]Co-NT-CB-NOTA revealed high tumor uptake, high tumor-to-background contrast, and sustained tumor retention (≤48 h after injection) in NTSR-1-positive tumors. Tumor uptake of [⁶⁴Cu]Cu-NT-CB-NOTA remained at 76.9% at 48 h after injection compared with uptake 1 h after injection in H1299 tumor models, and [⁵⁵Co]Co-NT-CB-NOTA was retained at 60.2% at 24 h compared with uptake 1 h after injection in HT29 tumor models. [⁶⁴Cu]Cu-NT-Sarcage also showed high tumor uptake with low background and high tumor retention 48 h after injection <b>Conclusion:</b> Tumor uptake and pharmacokinetic properties of NTSR-1-targeting radiopharmaceuticals were greatly improved when attached with different nitrogen-containing macrocyclic moieties. The study results suggest that NT-CB-NOTA labeled with either ⁶⁴Cu/⁶⁷Cu, ⁵⁵Co/^58mCo, or ⁶⁸Ga (effect of ¹⁷⁷Lu in tumor to be determined in future studies) and NT-Sarcage labeled with ⁶⁴Cu/⁶⁷Cu or ⁵⁵Co/^58mCo may be excellent diagnostic and therapeutic radiopharmaceuticals targeting NTSR-1-positive cancers. Also, the introduction of MA units to other ligands is warranted in future studies to test the generality of this approach.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast Activation Protein-Directed Imaging Outperforms ¹⁸F-FDG PET/CT in Malignant Mesothelioma: A Prospective, Single-Center, Observational Trial.","authors":"Lukas Kessler, Felix Schwaning, Martin Metzenmacher, Kim Pabst, Jens Siveke, Marija Trajkovic-Arsic, Benedikt Schaarschmidt, Marcel Wiesweg, Clemens Aigner, Till Plönes, Kaid Darwiche, Servet Bölükbas, Martin Stuschke, Lale Umutlu, Michael Nader, Dirk Theegarten, Rainer Hamacher, Wilfried E E Eberhardt, Martin Schuler, Ken Herrmann, Wolfgang P Fendler, Hubertus Hautzel","doi":"10.2967/jnumed.124.267473","DOIUrl":"10.2967/jnumed.124.267473","url":null,"abstract":"<p><p>The fibroblast activation protein (FAP) is highly expressed in tumor and stromal cells of mesothelioma and thus is an interesting imaging and therapeutic target. Previous data on PET imaging with radiolabeled FAP inhibitors (FAPIs) suggest high potential for superior tumor detection. Here, we report the data of a large malignant pleural mesothelioma cohort within a ⁶⁸Ga-FAPI46 PET observational trial (NCT04571086). <b>Methods:</b> Of 43 eligible patients with suspected or proven malignant mesothelioma, 41 could be included in the data analysis of the ⁶⁸Ga-FAPI46 PET observational trial. All patients underwent ⁶⁸Ga-FAPI46 PET/CT, contrast-enhanced CT, and ¹⁸F-FDG PET/CT. The primary study endpoint was the association of ⁶⁸Ga-FAPI46 PET uptake intensity and histopathologic FAP expression. Furthermore, secondary endpoints were detection rate and sensitivity, specificity, and positive and negative predictive values as compared with ¹⁸F-FDG PET/CT. Datasets were interpreted by 2 masked readers. <b>Results:</b> The primary endpoint was met, and the association between ⁶⁸Ga-FAPI46 SUV_max or SUV_peak and histopathologic FAP expression was significant (SUV_max: <i>r</i> = 0.49, <i>P</i> = 0.037; SUV_peak: <i>r</i> = 0.51, <i>P</i> = 0.030).⁶⁸Ga-FAPI46 and ¹⁸F-FDG showed similar sensitivity by histopathologic validation on a per-patient (100.0% vs. 97.3%) and per region (98.0% vs. 95.9%) basis. Per-region analysis revealed higher ⁶⁸Ga-FAPI46 than ¹⁸F-FDG specificity (81.1% vs. 36.8%) and positive predictive value (87.5% vs. 66.2%). <b>Conclusion:</b> We confirm an association of ⁶⁸Ga-FAPI46 uptake and histopathologic FAP expression in mesothelioma patients. Additionally, we report high sensitivity and superior specificity and positive predictive value for ⁶⁸Ga-FAPI46 versus ¹⁸F-FDG.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Associated with Myocardial Uptake on Oncologic Somatostatin PET Investigations and Differentiation from Myocardial Uptake of Acute Myocarditis.","authors":"Thomas Larive, Caroline Boursier, Marine Claudin, Jeanne Varlot, Laura Filippetti, Olivier Huttin, Véronique Roch, Laetitia Imbert, Matthieu Doyen, Aurélien Lambert, Damien Mandry, Zohra Lamiral, Elodie Chevalier, Pierre-Yves Marie","doi":"10.2967/jnumed.123.267219","DOIUrl":"10.2967/jnumed.123.267219","url":null,"abstract":"<p><p>Myocardial somatostatin PET uptake is observed not only in most patients with acute myocarditis (AM) but also in some oncology patients referred for routine somatostatin PET. This raises concerns about the specificity of somatostatin PET for detecting myocarditis. The current study aims to identify factors associated with the detection of myocardial uptake on somatostatin PET scans recorded for oncology indications and differential PET criteria that characterize myocardial uptake in AM patients. <b>Methods:</b> We analyzed factors associated with the detection of myocardial [⁶⁸Ga]Ga-DOTATOC uptake in 508 [⁶⁸Ga]Ga-DOTATOC PET scans from 178 patients, performed for confirmed or suspected oncologic disease (Onc-PET) and PET criteria that could differentiate myocardial [⁶⁸Ga]Ga-DOTATOC uptake in 31 patients with MRI-ascertained AM (AM-PET) from that in the Onc-PET group. <b>Results:</b> Significant myocardial uptake was detected in 137 (26.9%) Onc-PET scans and was independently associated with somatostatin analog treatment (exp(β), 0.805; 95% CI, 0.728-0.890; <i>P</i> < 0.001) and age (exp(β), 1.005; 95% CI, 1.001-1.009; <i>P</i> = 0.012). A comparable model was selected for predicting the myocardial-to-blood SUV_max ratio using somatostatin analog treatment (<i>P</i> < 0.001) and history of coronary artery disease (<i>P</i> = 0.022). Myocardial uptake was detected in 12.9% (25/193) of Onc-PET scans from patients treated with somatostatin analogs but in 43.4% (59/136) of untreated patients over the median age of 64 y. Myocardial uptake was apparent in all 31 AM-PET scans, with volume and intensity of uptake dramatically higher than in the 137 Onc-PET scans showing myocardial uptake. A myocardial-to-blood SUV_max ratio threshold of 2.20 provided a sensitivity of 87% (27/31) and a specificity of 88% (44/50) for differentiating myocardial uptake between the AM-PET group and an Onc-PET group restricted to patients with clinical characteristics comparable to those of patients in the AM-PET group (≤64 y of age, no coronary artery disease history, and no somatostatin agonists). A myocardial uptake volume threshold of 18 cm³ provided comparable diagnostic accuracy (sensitivity, 84% [26/31]; specificity, 94% [47/50]). <b>Conclusion:</b> Myocardial uptake was detected in 26.9% of somatostatin PET scans recorded for oncology indications. This rate was decreased by somatostatin analog treatments and increased in older individuals. However, somatostatin PET scans, analyzed with the quantitative criterion of uptake intensity or volume, are able to identify AM and to differentiate it from myocardial uptake of other origins.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Illuminating Cardiac Function: Heinz Schelbert Talks with Heiko Schöder and Johannes Czernin About a Pioneering Career in Nuclear Cardiology.","authors":"Heinrich Schelbert, Heiko Schöder, Johannes Czernin","doi":"10.2967/jnumed.124.268302","DOIUrl":"10.2967/jnumed.124.268302","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interreader and Intrareader Reproducibility of ¹⁸F-Flotufolastat Image Interpretation in Patients with Newly Diagnosed or Recurrent Prostate Cancer: Data from Two Phase 3 Prospective Multicenter Studies.","authors":"Phillip H Kuo, Giuseppe Esposito, Gary A Ulaner, Don Yoo, Katherine Zukotynski, Gregory C Ravizzini, Ross Penny, Matthew P Miller, Albert Chau, Phillip Davis, Brian F Chapin, David M Schuster","doi":"10.2967/jnumed.123.267306","DOIUrl":"10.2967/jnumed.123.267306","url":null,"abstract":"<p><p>Interreader and intrareader reproducibility of ¹⁸F-flotufolastat PET/CT scans in newly diagnosed and recurrent prostate cancer patients was assessed from masked image evaluations from two phase 3 studies. <b>Methods:</b> ¹⁸F-flotufolastat PET/CT images of newly diagnosed (<i>n</i> = 352) or recurrent (<i>n</i> = 389) patients were evaluated by 3 masked readers. Cohen κ was used to assess pairwise patient- and region-level interreader agreement. Agreement among all readers was assessed using Fleiss κ. Intrareader agreement between the first and repeat read (20% of images, ≥4 wk later) was assessed using Cohen κ. <b>Results:</b> Pairwise interreader agreement was 95% or better (newly diagnosed) and 75% or better (recurrent). The κ coefficients were impacted by the high-agreement-low-κ paradox: Cohen κ ranged from not estimable to 0.55, whereas Fleiss κ was 0.50 (newly diagnosed) and 0.41 (recurrent). Agreement was highest in the prostate of newly diagnosed patients (≥95%) and in the pelvic lymph nodes in recurrent patients (≥87%). Intrareader agreement was 86% or better across both populations. <b>Conclusion:</b> ¹⁸F-flotufolastat PET/CT images can be reliably interpreted, with a high degree of inter- and intrareader agreement.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}