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

{"title":"Theranostic GPA33-Pretargeted Radioimmunotherapy of Human Colorectal Carcinoma with a Bivalent ¹⁷⁷Lu-Labeled Radiohapten.","authors":"Brett A Vaughn, Sang-Gyu Lee, Daniela Burnes Vargas, Shin Seo, Sara S Rinne, Hong Xu, Hong-Fen Guo, Alexandre B Le Roux, Leah Gajecki, Simone Krebs, Guangbin Yang, Ouathek Ouerfelli, Pat B Zanzonico, Edward K Fung, Samantha St Jean, Sebastian E Carrasco, Achim Jungbluth, Nai Kong V Cheung, Steven M Larson, Darren R Veach, Sarah M Cheal","doi":"10.2967/jnumed.124.267685","DOIUrl":"10.2967/jnumed.124.267685","url":null,"abstract":"<p><p>Radiolabeled small-molecule DOTA-haptens can be combined with antitumor/anti-DOTA bispecific antibodies (BsAbs) for pretargeted radioimmunotherapy (PRIT). For optimized delivery of the theranostic γ- and β-emitting isotope <sup>177</sup>Lu with DOTA-based PRIT (DOTA-PRIT), bivalent Gemini (DOTA-Bn-thiourea-PEG4-thiourea-Bn-DOTA, aka (3,6,9,12-tetraoxatetradecane-1,14-diyl)bis(DOTA-benzyl thiourea)) was developed. <b>Methods:</b> Gemini was synthesized by linking 2 <i>S</i>-2-(4-isothiocyanatobenzyl)-DOTA molecules together via a 1,14-diamino-PEG4 linker. [<sup>177</sup>Lu]Lu-Gemini was prepared with no-carrier-added <sup>177</sup>LuCl<sub>3</sub> to a molar-specific activity of 123 GBq/μmol and radiochemical purity of more than 99%. The specificity of BsAb-<sup>177</sup>Lu-Gemini was verified in vitro. Subsequently, we evaluated biodistribution and whole-body clearance for [<sup>177</sup>Lu]Lu-Gemini and, for comparison, our gold-standard monovalent [<sup>177</sup>Lu]Lu-<i>S</i>-2-(4-aminobenzyl)-DOTA ([<sup>177</sup>Lu]Lu-DOTA-Bn) in naïve (tumor-free) athymic nude mice. For our proof-of-concept system, a 3-step pretargeting approach was performed with an established DOTA-PRIT regimen (anti-GPA33/anti-DOTA IgG-scFv BsAb, a clearing agent, and [<sup>177</sup>Lu]Lu-Gemini) in mouse models. <b>Results:</b> Initial in vivo studies showed that [<sup>177</sup>Lu]Lu-Gemini behaved similarly to [<sup>177</sup>Lu]Lu-DOTA-Bn, with almost identical blood and whole-body clearance kinetics, as well as biodistribution and mouse kidney dosimetry. Pretargeting [<sup>177</sup>Lu]Lu-Gemini to GPA33-expressing SW1222 human colorectal xenografts was highly effective, leading to absorbed doses of [<sup>177</sup>Lu]Lu-Gemini for blood, tumor, liver, spleen, and kidneys of 3.99, 455, 6.93, 5.36, and 14.0 cGy/MBq, respectively. Tumor-to-normal tissue absorbed-dose ratios (i.e., therapeutic indices [TIs]) for the blood and kidneys were 114 and 33, respectively. In addition, we demonstrate that the use of bivalent [<sup>177</sup>Lu]Lu-Gemini in DOTA-PRIT leads to improved TIs and augmented [<sup>177</sup>Lu]Lu-Gemini tumor uptake and retention in comparison to monovalent [<sup>177</sup>Lu]Lu-DOTA-Bn. Finally, we established efficacy in SW1222 tumor-bearing mice, demonstrating that a single injection of anti-GPA33 DOTA-PRIT with 44 MBq (1.2 mCi) of [<sup>177</sup>Lu]Lu-Gemini (estimated tumor-absorbed dose, 200 Gy) induced complete responses in 5 of 5 animals and a histologic cure in 2 of 5 (40%) animals. Moreover, a significant increase in survival compared with nontreated controls was noted (maximum tolerated dose not reached). <b>Conclusion:</b> We have developed a bivalent DOTA-radiohapten, [<sup>177</sup>Lu]Lu-Gemini, that showed improved radiopharmacology for DOTA-PRIT application. The use of bivalent [<sup>177</sup>Lu]Lu-Gemini in DOTA-PRIT, as opposed to monovalent [<sup>177</sup>Lu]Lu-DOTA-Bn, allows curative treatments with considerably less administered <","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1611-1618"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019929","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":"The Rise of Molecular Image-Guided Robotic Surgery.","authors":"Fijs W B van Leeuwen, Tessa Buckle, Matthias N van Oosterom, Daphne D D Rietbergen","doi":"10.2967/jnumed.124.267783","DOIUrl":"10.2967/jnumed.124.267783","url":null,"abstract":"<p><p>Following early acceptance by urologists, the use of surgical robotic platforms is rapidly spreading to other surgical fields. This empowerment of surgical perception via robotic advances occurs in parallel to developments in intraoperative molecular imaging. Convergence of these efforts creates a logical incentive to advance the decades-old image-guided robotics paradigm. This yields new radioguided surgery strategies set to optimally exploit the symbiosis between the growing clinical translation of robotics and molecular imaging. These strategies intend to advance surgical precision by increasing dexterity and optimizing surgical decision-making. In this state-of-the-art review, topic-related developments in chemistry (tracer development) and engineering (medical device development) are discussed, and future scientific robotic growth markets for molecular imaging are presented.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1505-1511"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592496","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":"Challenges with ¹⁷⁷Lu-PSMA-617 Radiopharmaceutical Therapy in Clinical Practice.","authors":"Hossein Jadvar, Amir Iravani, Lisa Bodei, Jeremie Calais","doi":"10.2967/jnumed.124.268023","DOIUrl":"https://doi.org/10.2967/jnumed.124.268023","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142304908","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":"The Translation of Dosimetry into Clinical Practice: What It Takes to Make Dosimetry a Mandatory Part of Clinical Practice.","authors":"Manuel Bardiès, Glenn Flux, Katarina Sjögreen Gleisner","doi":"10.2967/jnumed.124.267742","DOIUrl":"https://doi.org/10.2967/jnumed.124.267742","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142206","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":"Quantitative Assessments of Tumor Activity in a General Oncologic PET/CT Population: Which Metric Minimizes Tracer Uptake Time Dependence?","authors":"Semra Ince, Richard Laforest, Malak Itani, Vikas Prasad, Paul-Robert Derenoncourt, John P Crandall, Saeed Ashrafinia, Anne M Smith, Richard L Wahl, Tyler J Fraum","doi":"10.2967/jnumed.123.266469","DOIUrl":"10.2967/jnumed.123.266469","url":null,"abstract":"&lt;p&gt;&lt;p&gt;In oncologic PET, the SUV and standardized uptake ratio (SUR) of a viable tumor generally increase during the postinjection period. In contrast, the net influx rate (&lt;i&gt;K&lt;sub&gt;i&lt;/sub&gt;&lt;/i&gt; ), which is derived from dynamic PET data, should remain relatively constant. Uptake-time-corrected SUV (cSUV) and SUR (cSUR) have been proposed as uptake-time-independent, static alternatives to &lt;i&gt;K&lt;sub&gt;i&lt;/sub&gt;&lt;/i&gt; Our primary aim was to quantify the intrascan repeatability of &lt;i&gt;K&lt;sub&gt;i&lt;/sub&gt;&lt;/i&gt; , SUV, cSUV, SUR, and cSUR among malignant lesions on PET/CT. An exploratory aim was to assess the ability of cSUR to estimate &lt;i&gt;K&lt;sub&gt;i&lt;/sub&gt;&lt;/i&gt; &lt;b&gt;Methods:&lt;/b&gt; This prospective, single-center study enrolled adults undergoing standard-of-care oncologic PET/CT. SUV and &lt;i&gt;K&lt;sub&gt;i&lt;/sub&gt;&lt;/i&gt; images were reconstructed from dynamic PET data obtained before (∼35-50 min after injection) and after (∼75-90 min after injection) standard-of-care imaging. Tumors were manually segmented. Quantitative metrics were extracted. cSUVs and cSURs were calculated for a 60-min postinjection reference uptake time. The magnitude of the intrascan test-retest percent change (test-retest |%Δ|) was calculated. Coefficients of determination (&lt;i&gt;R&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt;) and intraclass correlation coefficients (ICC) were also computed. Differences between metrics were assessed via the Wilcoxon signed-rank test (α, 0.05). &lt;b&gt;Results:&lt;/b&gt; This study enrolled 78 subjects; 41 subjects (mean age, 63.8 y; 24 men) with 116 lesions were analyzed. For both tracers, SUV&lt;sub&gt;max&lt;/sub&gt; and maximum SUR (SUR&lt;sub&gt;max&lt;/sub&gt;) had large early-to-late increases (i.e., poor intrascan repeatability). Among [&lt;sup&gt;18&lt;/sup&gt;F]FDG-avid lesions (&lt;i&gt;n&lt;/i&gt; = 93), there were no differences in intrascan repeatability (median test-retest |%Δ|; ICC) between the maximum &lt;i&gt;K&lt;sub&gt;i&lt;/sub&gt;&lt;/i&gt; (&lt;i&gt;K&lt;sub&gt;i&lt;/sub&gt;&lt;/i&gt; &lt;sub&gt;,max&lt;/sub&gt;) (13%; 0.97) and either the maximum cSUV (cSUV&lt;sub&gt;max&lt;/sub&gt;) (12%, &lt;i&gt;P&lt;/i&gt; = 0.90; 0.96) or the maximum cSUR (cSUR&lt;sub&gt;max&lt;/sub&gt;) (13%, &lt;i&gt;P&lt;/i&gt; = 0.67; 0.94). For DOTATATE-avid lesions (&lt;i&gt;n&lt;/i&gt; = 23), there were no differences in intrascan repeatability between the &lt;i&gt;K&lt;sub&gt;i&lt;/sub&gt;&lt;/i&gt; &lt;sub&gt;,max&lt;/sub&gt; (11%; 0.98) and either the cSUV&lt;sub&gt;max&lt;/sub&gt; (13%, &lt;i&gt;P&lt;/i&gt; = 0.41; 0.98) or the cSUR&lt;sub&gt;max&lt;/sub&gt; (11%, &lt;i&gt;P&lt;/i&gt; = 0.08; 0.94). The SUV&lt;sub&gt;max&lt;/sub&gt;, cSUV&lt;sub&gt;max&lt;/sub&gt;, SUR&lt;sub&gt;max&lt;/sub&gt;, and cSUR&lt;sub&gt;max&lt;/sub&gt; were all strongly correlated with the &lt;i&gt;K&lt;sub&gt;i&lt;/sub&gt;&lt;/i&gt; &lt;sub&gt;,max&lt;/sub&gt; for both [&lt;sup&gt;18&lt;/sup&gt;F]FDG (&lt;i&gt;R&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt;, 0.81-0.92) and DOTATATE (&lt;i&gt;R&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt;, 0.88-0.96), but the cSUR&lt;sub&gt;max&lt;/sub&gt; provided the best agreement with the &lt;i&gt;K&lt;sub&gt;i&lt;/sub&gt;&lt;/i&gt; &lt;sub&gt;,max&lt;/sub&gt; across early-to-late time points for [&lt;sup&gt;18&lt;/sup&gt;F]FDG (ICC, 0.69-0.75) and DOTATATE (ICC, 0.90-0.91). &lt;b&gt;Conclusion:&lt;/b&gt; &lt;i&gt;K&lt;sub&gt;i&lt;/sub&gt;&lt;/i&gt; &lt;sub&gt;,max&lt;/sub&gt;, cSUV&lt;sub&gt;max&lt;/sub&gt;, and cSUR&lt;sub&gt;max&lt;/sub&gt; had low uptake time dependence compared with SUV&lt;sub&gt;max&lt;/sub&gt; and SUR&lt;sub&gt;max&lt;/sub&gt; The &lt;i&gt;K&lt;sub&gt;i&lt;/sub","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1349-1356"},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984248","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":"Single Chelator-Minibody Theranostic Agents for ⁸⁹Zr PET Imaging and ¹⁷⁷Lu Radiopharmaceutical Therapy of PSMA-Expressing Prostate Cancer.","authors":"Khanh-Van Ho, David S Tatum, Lisa Watkinson, Terry Carmack, Fang Jia, Alessandro Mascioni, Charles A Maitz, Darren Magda, Carolyn J Anderson","doi":"10.2967/jnumed.124.267667","DOIUrl":"10.2967/jnumed.124.267667","url":null,"abstract":"<p><p>Here we describe an anti-prostate-specific membrane antigen (PSMA) minibody (IAB2MA) conjugated to an octadentate, macrocyclic chelator based on four 1-hydroxypyridin-2-one coordinating units (Lumi804 [L804]) labeled with ⁸⁹Zr (PET imaging) and ¹⁷⁷Lu (radiopharmaceutical therapy), with the goal of developing safer and more efficacious treatment options for prostate cancer. <b>Methods:</b> L804 was compared with the current gold standard chelators, DOTA and deferoxamine (DFO), conjugated to IAB2MA for radiolabeling with ¹⁷⁷Lu and ⁸⁹Zr in cell binding, preclinical biodistribution, imaging, dosimetry, and efficacy studies in the PSMA-positive PC3-PIP tumor-bearing mouse model of prostate cancer. <b>Results:</b> Quantitative radiolabeling (>99% radiochemical yield) of L804-IAB2MA with ¹⁷⁷Lu or ⁸⁹Zr was achieved at ambient temperature in under 30 min, comparable to ⁸⁹Zr labeling of DFO-IAB2MA. In contrast, DOTA-IAB2MA was radiolabeled with ¹⁷⁷Lu for 30 min at 37°C in approximately 90% radiochemical yield, requiring further purification. Using europium(III) as a luminescent surrogate, high binding affinity of Eu-L804-IAB2MA to PSMA was demonstrated in PC3-PIP cells (dissociation constant, 4.6 ± 0.6 nM). All 4 radiolabeled constructs showed significantly higher levels of internalization after 30 min in the PC3-PIP cells than in PSMA-negative PC3-FLU cells. The accumulation of ¹⁷⁷Lu- and ⁸⁹Zr-L804-IAB2MA in PC3-PIP tumors and all organs examined (i.e., heart, liver, spleen, kidney, muscle, salivary glands, lacrimal glands, carcass, and bone) was significantly lower than that of ¹⁷⁷Lu-DOTA-IAB2MA and ⁸⁹Zr-DFO-IAB2MA at 96 and 72 h after injection, respectively. Generally, SPECT/CT and PET/CT imaging data showed no significant difference in the SUV_mean of the tumors or muscle between the radiotracers. Dosimetry analysis via both organ-level and voxel-level dose calculation methods indicated significantly higher absorbed doses of ¹⁷⁷Lu-DOTA-IAB2MA in tumors, kidney, liver, muscle, and spleen than of ¹⁷⁷Lu-L804-IAB2MA. PC3-PIP tumor-bearing mice treated with single doses of ¹⁷⁷Lu-L804-IAB2MA (18.4 or 22.2 MBq) exhibited significantly prolonged survival and reduced tumor volume compared with unlabeled minibody control. No significant difference in survival was observed between groups of mice treated with ¹⁷⁷Lu-L804-IAB2MA or ¹⁷⁷Lu-DOTA-IAB2MA (18.4 or 22.2 MBq). Treatment with ¹⁷⁷Lu-L804-IAB2MA resulted in lower absorbed doses in tumors and less toxicity than that of ¹⁷⁷Lu-DOTA-IAB2MA. <b>Conclusion:</b> ⁸⁹Zr- and ¹⁷⁷Lu-L804-IAB2MA may be a promising theranostic pair for imaging and therapy of prostate cancer.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1435-1442"},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984249","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":"Role of ⁶⁴CuCl₂ PET/CT in Detecting and Staging Muscle-Invasive Bladder Cancer: Comparison with Contrast-Enhanced CT and ¹⁸F-FDG PET/CT.","authors":"Arnoldo Piccardo, Gianluca Bottoni, Cristina Puppo, Michela Massollo, Martina Ugolini, Mehrdad Shoushtari Zadeh Naseri, Enrico Melani, Laura Tomasello, Monica Boitano, Andrea DeCensi, Beatrice Sambucco, Fabio Campodonico, Vania Altrinetti, Marco Ennas, Alessia Urru, Carlo Luigi Augusto Negro, Luca Timossi, Giorgio Treglia, Carlo Introini, Francesco Fiz","doi":"10.2967/jnumed.124.267474","DOIUrl":"10.2967/jnumed.124.267474","url":null,"abstract":"<p><p>Molecular imaging of muscle-invasive bladder cancer (MBC) is restricted to its locoregional and distant metastases, since most radiopharmaceuticals have a urinary excretion that limits the visualization of the primary tumor. ⁶⁴CuCl₂ _, a positron-emitting radiotracer with nearly exclusive biliary elimination, could be well suited to exploring urinary tract neoplasms. In this study, we evaluated the feasibility of ⁶⁴CuCl₂-based staging of patients with MBC; furthermore, we compared the diagnostic capability of this method with those of the current gold standards, that is, contrast-enhanced CT (ceCT) and ¹⁸F-FDG PET/CT. <b>Methods:</b> We prospectively enrolled patients referred to our institution for pathology-confirmed MBC staging/restaging between September 2021 and January 2023. All patients underwent ceCT, ¹⁸F-FDG, and ⁶⁴CuCl₂ PET/CT within 2 wk. Patient-based analysis and lesion-based analysis were performed for all of the potentially affected districts (overall, bladder wall, lymph nodes, skeleton, liver, lung, and pelvic soft tissue). <b>Results:</b> Forty-two patients (9 women) were enrolled. Thirty-six (86%) had evidence of disease, with a total of 353 disease sites. On patient-based analysis, ceCT and ⁶⁴CuCl₂ PET/CT showed higher sensitivity than ¹⁸F-FDG PET/CT in detecting the primary tumor (<i>P</i> < 0.001); moreover, ⁶⁴CuCl₂ PET/CT was slightly more sensitive than ¹⁸F-FDG PET/CT in disclosing soft-tissue lesions (<i>P</i> < 0.05). Both PET methods were more specific and accurate than ceCT in classifying nodal lesions (<i>P</i> < 0.05). On lesion-based analysis, ⁶⁴CuCl₂ PET/CT outperformed ¹⁸F-FDG PET/CT and ceCT in detecting disease localizations overall (<i>P</i> < 0.001), in the lymph nodes (<i>P</i> < 0.01), in the skeleton (<i>P</i> < 0.001), and in the soft tissue (<i>P</i> < 0.05). <b>Conclusion:</b> ⁶⁴CuCl₂ PET/CT appears to be a sensitive modality for staging/restaging of MBC and might represent a \"one-stop shop\" diagnostic method in these scenarios.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1357-1363"},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763628","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":"Total-Body Dynamic Imaging and Kinetic Modeling of [¹⁸F]F-AraG in Healthy Individuals and a Non-Small Cell Lung Cancer Patient Undergoing Anti-PD-1 Immunotherapy.","authors":"Negar Omidvari, Jelena Levi, Yasser G Abdelhafez, Yiran Wang, Lorenzo Nardo, Megan E Daly, Guobao Wang, Simon R Cherry","doi":"10.2967/jnumed.123.267003","DOIUrl":"10.2967/jnumed.123.267003","url":null,"abstract":"<p><p>Immunotherapies, especially checkpoint inhibitors such as anti-programmed cell death protein 1 (anti-PD-1) antibodies, have transformed cancer treatment by enhancing the immune system's capability to target and kill cancer cells. However, predicting immunotherapy response remains challenging. ¹⁸F-arabinosyl guanine ([¹⁸F]F-AraG) is a molecular imaging tracer targeting activated T cells, which may facilitate therapy response assessment by noninvasive quantification of immune cell activity within the tumor microenvironment and elsewhere in the body. The aim of this study was to obtain preliminary data on total-body pharmacokinetics of [¹⁸F]F-AraG as a potential quantitative biomarker for immune response evaluation. <b>Methods:</b> The study consisted of 90-min total-body dynamic scans of 4 healthy subjects and 1 non-small cell lung cancer patient who was scanned before and after anti-PD-1 immunotherapy. Compartmental modeling with Akaike information criterion model selection was used to analyze tracer kinetics in various organs. Additionally, 7 subregions of the primary lung tumor and 4 mediastinal lymph nodes were analyzed. Practical identifiability analysis was performed to assess the reliability of kinetic parameter estimation. Correlations of the SUV_mean, the tissue-to-blood SUV ratio (SUVR), and the Logan plot slope (<i>K</i> _Logan) with the total volume of distribution (<i>V</i> _T) were calculated to identify potential surrogates for kinetic modeling. <b>Results:</b> Strong correlations were observed between <i>K</i> _Logan and SUVR with <i>V</i> _T, suggesting that they can be used as promising surrogates for <i>V</i> _T, especially in organs with a low blood-volume fraction. Moreover, practical identifiability analysis suggested that dynamic [¹⁸F]F-AraG PET scans could potentially be shortened to 60 min, while maintaining quantification accuracy for all organs of interest. The study suggests that although [¹⁸F]F-AraG SUV images can provide insights on immune cell distribution, kinetic modeling or graphical analysis methods may be required for accurate quantification of immune response after therapy. Although SUV_mean showed variable changes in different subregions of the tumor after therapy, the SUVR, <i>K</i> _Logan, and <i>V</i> _T showed consistent increasing trends in all analyzed subregions of the tumor with high practical identifiability. <b>Conclusion:</b> Our findings highlight the promise of [¹⁸F]F-AraG dynamic imaging as a noninvasive biomarker for quantifying the immune response to immunotherapy in cancer patients. Promising total-body kinetic modeling results also suggest potentially wider applications of the tracer in investigating the role of T cells in the immunopathogenesis of diseases.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1481-1488"},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877011","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":"⁶¹Cu-PSMA-Targeted PET for Prostate Cancer: From Radiotracer Development to First-in-Human Imaging.","authors":"Tais Basaco Bernabeu, Rosalba Mansi, Luigi Del Pozzo, Sandra Zanger, Raghuvir H Gaonkar, Lisa McDougall, Francesco De Rose, Leila Jaafar-Thiel, Michael Herz, Matthias Eiber, Gary A Ulaner, Wolfgang A Weber, Melpomeni Fani","doi":"10.2967/jnumed.123.267126","DOIUrl":"10.2967/jnumed.123.267126","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The demand for PET tracers that target prostate-specific membrane antigen (PSMA) continues to increase. Meeting this demand with approved &lt;sup&gt;68&lt;/sup&gt;Ga- and &lt;sup&gt;18&lt;/sup&gt;F-labeled PSMA tracers is challenging outside of major urban centers. This is because the short physical half-life of these radionuclides makes it necessary to produce them near their sites of usage. To overcome this challenge, we propose cyclotron-produced &lt;sup&gt;61&lt;/sup&gt;Cu for labeling PSMA PET tracers. &lt;sup&gt;61&lt;/sup&gt;Cu can be produced on a large scale, and its 3.33-h half-life allows shipping over considerably longer distances than possible for &lt;sup&gt;68&lt;/sup&gt;Ga and &lt;sup&gt;18&lt;/sup&gt;F. Production of true theranostic twins using &lt;sup&gt;61&lt;/sup&gt;Cu and the β&lt;sup&gt;-&lt;/sup&gt;-emitter &lt;sup&gt;67&lt;/sup&gt;Cu is also feasible. &lt;b&gt;Methods:&lt;/b&gt; PSMA-I&T (DOTAGA-(l-y)fk(sub-KuE)) and its derivative in which the DOTAGA chelator was replaced by NODAGA (NODAGA-(l-y)fk(sub-KuE)), herein reported as DOTAGA-PSMA-I&T and NODAGA-PSMA-I&T, respectively, were labeled with &lt;sup&gt;61&lt;/sup&gt;Cu and compared with [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-DOTAGA-PSMA-I&T, [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-NODAGA-PSMA-I&T, [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-PSMA-11, and [&lt;sup&gt;18&lt;/sup&gt;F]PSMA-1007. In vitro (lipophilicity, affinity, cellular uptake, and distribution) and in vivo (PET/CT, biodistribution, and stability) studies were performed in LNCaP cells and xenografts. Human dosimetry estimates were calculated for [&lt;sup&gt;61&lt;/sup&gt;Cu]Cu-NODAGA-PSMA-I&T. First-in-human imaging with [&lt;sup&gt;61&lt;/sup&gt;Cu]Cu-NODAGA-PSMA-I&T was performed in a patient with metastatic prostate cancer. &lt;b&gt;Results:&lt;/b&gt; [&lt;sup&gt;61&lt;/sup&gt;Cu]Cu-DOTAGA-PSMA-I&T and [&lt;sup&gt;61&lt;/sup&gt;Cu]Cu-NODAGA-PSMA-I&T were synthesized with radiochemical purity of more than 97%, at an apparent molar activity of 24 MBq/nmol, without purification after labeling. In vitro, natural Cu (&lt;sup&gt;nat&lt;/sup&gt;Cu)-DOTAGA-PSMA-I&T and &lt;sup&gt;nat&lt;/sup&gt;Cu-NODAGA-PSMA-I&T showed high affinity for PSMA (inhibitory concentration of 50%, 11.2 ± 2.3 and 9.3 ± 1.8 nM, respectively), although lower than the reference &lt;sup&gt;nat&lt;/sup&gt;Ga-PSMA-11 (inhibitory concentration of 50%, 2.4 ± 0.4 nM). Their cellular uptake and distribution were comparable to those of [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-PSMA-11. In vivo, [&lt;sup&gt;61&lt;/sup&gt;Cu]Cu-NODAGA-PSMA-I&T showed significantly lower uptake in nontargeted tissues than [&lt;sup&gt;61&lt;/sup&gt;Cu]Cu-DOTAGA-PSMA-I&T and higher tumor uptake (14.0 ± 5.0 percentage injected activity per gram of tissue [%IA/g]) than [&lt;sup&gt;61&lt;/sup&gt;Cu]Cu-DOTAGA-PSMA-I&T (6.06 ± 0.25 %IA/g, &lt;i&gt;P&lt;/i&gt; = 0.0059), [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-PSMA-11 (10.2 ± 1.5 %IA/g, &lt;i&gt;P&lt;/i&gt; = 0.0972), and [&lt;sup&gt;18&lt;/sup&gt;F]PSMA-1007 (9.70 ± 2.57 %IA/g, &lt;i&gt;P&lt;/i&gt; = 0.080) at 1 h after injection. Tumor uptake was also higher for [&lt;sup&gt;61&lt;/sup&gt;Cu]Cu-NODAGA-PSMA-I&T at 4 h after injection (10.7 ± 3.3 %IA/g) than for [&lt;sup&gt;61&lt;/sup&gt;Cu]Cu-DOTAGA-PSMA-I&T (4.88 ± 0.63 %IA/g, &lt;i&gt;P&lt;/i&gt; = 0.0014) and [&lt;sup&gt;18&lt;/sup&gt;F]PSMA-1007 (6.28 ± 2.19 %IA/g, &lt;i&gt;P&lt;/i&gt; = 0.0145). Tumor-to-nontumor ratios of [&lt;sup&gt;61&lt;/sup&gt;C","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1427-1434"},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725323","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":"The Potential Value of Functional Adrenal Imaging in Primary Aldosterone.","authors":"Benjamin L Viglianti, Allen Brooks","doi":"10.2967/jnumed.124.267966","DOIUrl":"10.2967/jnumed.124.267966","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1495"},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763629","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}