Nuclear medicine and biology最新文献

{"title":"Development of a novel xCT transporter imaging using a radiopharmaceutical with inhibitor-type compounds","authors":"Kakeru Sato ,&nbsp;Jundai Yamagata ,&nbsp;Yuka Hirayama ,&nbsp;Yuna Hamada ,&nbsp;Jianwei Yao ,&nbsp;Asuka Mizutani ,&nbsp;Masato Kobayashi ,&nbsp;Ryuichi Nishii ,&nbsp;Naoto Shikano ,&nbsp;Munetaka Kunishima ,&nbsp;Keiichi Kawai","doi":"10.1016/j.nucmedbio.2026.109625","DOIUrl":"10.1016/j.nucmedbio.2026.109625","url":null,"abstract":"<div><h3>Background</h3><div>The cystine/glutamate antiporter xCT has attracted attention due to its role in maintaining redox homeostasis. Noninvasive techniques for visualizing xCT expression in tumors provide valuable diagnostic information for evaluating tumor biology. Therefore, we developed and evaluated a novel SPECT radiopharmaceutical to visualize xCT expression in cancer cells based on inhibitors.</div></div><div><h3>Methods</h3><div>We designed and synthesized a radioiodinated SSZ derivative ([¹²⁵I]I-SSZd), based on the structure of sulfasalazine (SSZ)—an xCT inhibitor. We radioiodinated 4-hydroxy-<em>L</em>-phenylglycine (L-HPG) and 4-hydroxy-<em>D</em>-phenylglycine (D-HPG) to synthesize [¹²⁵I]I-L-HPG and [¹²⁵I]I-D-HPG, respectively. The affinities of [¹²⁵I]I-SSZd, [¹²⁵I]I-L-HPG, and [¹²⁵I]I-D-HPG to xCT were evaluated using SSZ and cystine inhibition assays in two human-derived colon cancer cell lines (LS180 and DLD-1). xCT expression was quantified using real-time polymerase chain reaction. <em>In vivo</em>, the biodistribution of [¹²⁵I]I-L-HPG was examined in tumor-bearing mice. Stability analysis was performed in mice liver and kidney homogenates.</div></div><div><h3>Results</h3><div>[¹²⁵I]I-L-HPG showed high affinity for xCT. [¹²⁵I]I-D-HPG exhibited some affinity for xCT. xCT was not involved in [¹²⁵I]I-SSZd accumulation. The gene expression levels of xCT were higher in LS180 than in DLD-1 cells. [¹²⁵I]I-L-HPG and [¹²⁵I]I-D-HPG showed high accumulation in LS180 cells. [¹²⁵I]I-L-HPG showed higher accumulation than [¹²⁵I]I-D-HPG in both cell lines. In the kidneys, [¹²⁵I]I-L-HPG accumulation decreased over time. In the thyroid, [¹²⁵I]I-L-HPG accumulation increased over time; however, deiodination did not occur in mice. Tumor-to-muscle ratio was &gt;2.0 at almost all timepoints for both types of tumor-bearing mice, and the maximum tumor-to-large intestine ratio reached 4.0 in LS180 tumors with high xCT expression.</div></div><div><h3>Conclusion</h3><div>In tumors, [¹²⁵I]I-L-HPG shows promise as a radiopharmaceutical by exhibiting high affinity for xCT.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"156 ","pages":"Article 109625"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147802222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous association of different forms of non-conjugated astatine-211 to serum albumin","authors":"Emma Aneheim ,&nbsp;Sture Lindegren ,&nbsp;Holger Jensen ,&nbsp;Tom Bäck","doi":"10.1016/j.nucmedbio.2026.109608","DOIUrl":"10.1016/j.nucmedbio.2026.109608","url":null,"abstract":"<div><h3>Aim/introduction</h3><div>Astatine-211 is one of the alpha-particle emitting nuclides investigated for use within Targeted Alpha Therapy (TAT) of disseminated cancer. In previous studies, a difference in blood clearance has been observed when comparing astatinated compounds with their iodinated counterparts. This has been explained by a potentially prolonged retention in the blood by present free astatine. This study examined the spontaneous binding of non-conjugated astatine to albumin under physiological conditions in vitro and compared it to that of iodine. Additionally, the in vivo blood circulation patterns of free astatine were assessed and contrasted with those of iodine.</div></div><div><h3>Materials and methods</h3><div>Astatine solutions were formulated following dry distillation and evaporation to dryness of astatine solvated in CHCl₃. In vitro evaluation of astatine and iodine association to albumin was mainly performed using size exclusion chromatography applying both disposable columns (PD10 and NAP10) as well as an FPLC system (ÄKTA) with online UV detection and activity fraction collection. Also methanol precipitation and radio-TLC methods were used for analysis. In vivo evaluation was performed using furry BALB/C mice (3/group) with both i.v. and i.p. injection of astatine, followed by sequential blood sampling from the tail vein and biodistribution.</div></div><div><h3>Results</h3><div>Oxidized and unmodified forms of free astatine display a significantly higher and more rapid association to albumin in vitro compared to reduced forms, with &gt;97% compared to &lt;25% associated after 10 min. Both the corresponding oxidized and reduced forms of iodine display a very low and slow association to albumin with &lt;5% associated after 40 min. Oxidized, unmodified and reduced astatine show very similar blood profiles over time as well as a similar uptake in biodistribution after 20–22 h following i.p. injection. Upon i.v. injection a larger difference in blood profiles between the species could be observed, which in turn was different compared to the curve obtained after i.p. injection. In addition, an unexpected uptake of astatide in stomach was found. In all cases the blood profile and biodistribution of astatine was significantly different compared to iodine, which displayed a greater and more rapid blood clearance and specific accumulation in thyroid.</div></div><div><h3>Conclusion</h3><div>Different forms of unbound astatine differ in their association to albumin. However, all investigated forms of free astatine associates to albumin to a much higher degree than iodine. This behavior could explain the prolonged blood circulation of free astatine compared to iodine.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"154 ","pages":"Article 109608"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Substitution matters: Comparison of four N,1,4-tri(methoxy-2-hydroxybenzyl)-DAZA ligands as potential PET/CT liver imaging agents","authors":"Anne Zenner ,&nbsp;Thomas Winkens ,&nbsp;Marta Pomraenke ,&nbsp;Steffen Wiegand ,&nbsp;Martin Freesmeyer ,&nbsp;Friederike Hüttner ,&nbsp;Wolfgang Weigand ,&nbsp;Birgit Weber ,&nbsp;Julia Greiser","doi":"10.1016/j.nucmedbio.2026.109604","DOIUrl":"10.1016/j.nucmedbio.2026.109604","url":null,"abstract":"<div><div>Four regioisomers of [⁶⁸Ga]Ga-TMoS-DAZA, a PET/CT radio tracer for liver function imaging, were studied as candidates of potentially improved hepatobiliary biokinetics. Liver uptake and biliary clearance behavior were compared using an in ovo model based on ostrich eggs for PET/CT imaging and ex vivo biodistribution analysis. The tracer lipophilicity was evaluated via logD determination. The experiments showed remarkable differences between the four tracers concerning their maximum liver uptake, percentage of tracer cleared via the biliary tract and their respective logD values.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"154 ","pages":"Article 109604"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an automated one-step radiolabeling procedure for a PSMA-targeted radiotherapeutic for prostate cancer","authors":"Meltem Ocak ,&nbsp;Kanishka Sikligar ,&nbsp;Michael Pun ,&nbsp;Khanh-Van Ho ,&nbsp;Xiaoxi Ling ,&nbsp;Valerie N. Carroll ,&nbsp;Jaime Simón ,&nbsp;Melody D. Fulton ,&nbsp;Hunter N. Bomba ,&nbsp;Clifford E. Berkman ,&nbsp;Beatrice C. Langton-Webster ,&nbsp;Carolyn J. Anderson","doi":"10.1016/j.nucmedbio.2026.109607","DOIUrl":"10.1016/j.nucmedbio.2026.109607","url":null,"abstract":"<div><h3>Background</h3><div>CTT1403 (¹⁷⁷Lu-CTT2001), an irreversible phosphoramidate PSMA inhibitor developed by Cancer Targeted Technology, was initially synthesized using a two-step radiolabeling method and has previously been evaluated in first-in-human studies. This two-step approach protected the phosphoramidate pharmacophore—containing a temperature- and pH-labile P<img>N bond—from the harsh conditions required for lutetium-177 (¹⁷⁷Lu) chelation. Although the final chemical structure of CTT1403 is identical regardless of the radiolabeling route, it was not clear that CTT2001 could tolerate one-step labeling conditions while preserving PSMA-binding integrity. Therefore, the aim of the study was to develop, optimize, and automate a one-step radiolabeling method for CTT1403 and to confirm that the resulting product is biologically equivalent and exhibits comparable in vitro and in vivo behavior to CTT1403 produced by the original two-step process.</div></div><div><h3>Methods</h3><div>CTT2001 was synthesized and radiolabeled with ¹⁷⁷Lu using an optimized one-step procedure that was subsequently automated on a Trasis AllinOne synthesizer. Radiochemical purity, stability, cellular uptake/internalization, and biodistribution in PC3-PIP tumor-bearing mice were evaluated.</div></div><div><h3>Results</h3><div>CTT1403 synthesized via the one-step method demonstrated cellular uptake and internalization in PC3-PIP cells, as well as in vivo biodistribution in PC3-PIP tumor–bearing mice, that were comparable to those of the two-step–labeled product. The one-step procedure was successfully automated on the Trasis All-in-One synthesizer, producing CTT1403 with a radiochemical yield of 86.5 ± 4.27% (<em>n</em> = 3), a molar activity of 30.3 ± 1.11 MBq/nmol, and a radiochemical purity of 97.6 ± 0.80% (n = 3) in a total synthesis time of 38 min. The final product remained stable for at least 24 h at −4 °C and −20 °C.</div></div><div><h3>Conclusions</h3><div>The one-step radiolabeling method yields CTT1403 that is biologically equivalent to the two-step product and can be reliably produced using fully automated synthesis. This streamlined, efficient, and reproducible approach supports routine clinical manufacturing of CTT1403.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"154 ","pages":"Article 109607"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial resolution and image quality of radionuclides for PET imaging","authors":"Sharon L. Samuel ,&nbsp;Solana Fernandez ,&nbsp;Shelbie J. Cingoranelli ,&nbsp;Jennifer M. Pyles ,&nbsp;Jennifer L. Bartels ,&nbsp;Hailey A. Houson ,&nbsp;Yun Lu ,&nbsp;Brian D. Wright ,&nbsp;Norio Yasui ,&nbsp;Anna G. Sorace ,&nbsp;Suzanne E. Lapi","doi":"10.1016/j.nucmedbio.2026.109612","DOIUrl":"10.1016/j.nucmedbio.2026.109612","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to characterize and compare the saturation limits, spatial resolution, and image quality of various conventional and emerging positron-emitting radionuclides using a preclinical PET/CT scanner. By characterizing the performance of these radionuclides, the study sought to provide insights into their utility in high-resolution PET imaging.</div></div><div><h3>Methods</h3><div>Radionuclides (¹⁸F, ⁴³Sc, ⁴⁵Ti, ⁴⁸V, ⁵²Mn, ⁵⁵Co, ⁶⁴Cu, ⁶⁸Ga, ⁸⁹Zr) were evaluated on a GNEXT PET/CT scanner (Xodus Imaging, Torrance, CA) using saturation and Derenzo phantoms. Saturation was assessed by measuring the deviation between the actual and the region of interest (ROI) activity at varying concentrations of each radionuclide. Spatial resolution was quantified using full-width half maximum (FWHM) measurements from intensity profiles across six Derenzo phantom diameter sizes (1.2 mm–4.8 mm). Signal-to-noise ratios (SNRs) were calculated as a measure of image quality and Bland-Altman plots were used to assess the repeatability of resolution measurements. Statistical comparisons of test-retest were done to evaluate differences in accuracy and consistency across radionuclides.</div></div><div><h3>Results</h3><div>Saturation analysis revealed a broad range of limits across radionuclides, with ⁶⁴Cu having the highest saturation threshold near 2 mCi (74 MBq), while ⁵²Mn exhibited the lowest at approximately 250 μCi (9.25 MBq). Spatial resolution was inversely related to positron energy, with radionuclides like ¹⁸F and ⁶⁴Cu producing clear images down to rod sizes of 1.6 mm compared to ⁶⁸Ga and ⁵⁵Co, which showed blurring at the same rod size. SNR analysis confirmed the superior image quality of lower-energy radionuclides, particularly for smaller structures, visually resolvable to 1.6 mm. Bland-Altman analysis showed that across the combination of rod sizes, ¹⁸F displayed improved repeatability in resolution measurements compared to ⁶⁸Ga (standard errors of 0.03 and 0.15, respectively).</div></div><div><h3>Conclusion</h3><div>This study demonstrates that the physical properties of radionuclides, particularly positron energy, significantly affected PET image quality, spatial resolution, and saturation thresholds. Lower-energy radionuclides like ¹⁸F and ⁵²Mn are optimal for high-resolution applications, while higher energy radionuclides are better suited for high-activity imaging. These findings provide valuable guidance for optimizing radionuclide selection in preclinical and clinical PET imaging studies.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"154 ","pages":"Article 109612"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NMB Innovators Series Professor Dae Yoon Chi, Ph.D.: Understanding of 18F-chemistry and its applications toward drug developments used in diagnosis and therapeutics","authors":"Hee Seup Kil ,&nbsp;Byung Chul Lee ,&nbsp;Dong Wook Kim ,&nbsp;Kyo Chul Lee","doi":"10.1016/j.nucmedbio.2026.109624","DOIUrl":"10.1016/j.nucmedbio.2026.109624","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"154 ","pages":"Article 109624"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147739898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implemented one-pot two step fully automated synthesis of [18F]FPIA for metabolic imaging applications","authors":"José S. Enriquez ,&nbsp;Vincenzo Paolillo ,&nbsp;Ryan Armijo ,&nbsp;Aldo Morales ,&nbsp;Peter D.A. Shepherd ,&nbsp;Muxin Wang ,&nbsp;Pratip K. Bhattacharya ,&nbsp;Federica Pisaneschi","doi":"10.1016/j.nucmedbio.2026.109605","DOIUrl":"10.1016/j.nucmedbio.2026.109605","url":null,"abstract":"<div><h3>Background</h3><div>[¹⁸F]Fluoropivalate ([¹⁸F]FPIA), also known as ¹⁸F-pivalate or ¹⁸F-RAD101, is the fluorinated analogue of pivalic acid and has shown promise in ongoing clinical trials for the detection of brain metastases. The original synthesis of [¹⁸F]FPIA involved a two-step procedure that was not fully automated, limiting its suitability for large-scale or GMP production. A subsequent report described an improved two-step, one-pot synthesis on a cassette-based module, although with certain limitations. Here, we present an optimized two-step, one-pot synthesis of [¹⁸F]FPIA using a vial-based automated synthesizer and demonstrate its successful implementation under GMP conditions. We also report [¹⁸F]FPIA-PET imaging in prostate cancer patient-derived xenograft (PDX) models.</div></div><div><h3>Results</h3><div>[¹⁸F]FPIA was successfully produced with the optimized synthetic strategy with a total synthesis time of 75 min and a 25.4 ± 3.8% (<em>n</em> = 9) activity yield at end of synthesis (EOS), with &gt;99% radiochemical purity. In a GMP setting, the scale-up synthesis was successful with a 37 ± 9% (<em>n</em> = 37) activity yield at EOS and a &gt; 99% radiochemical purity. In the proof-of-concept PET imaging study of [¹⁸F]FPIA in androgen receptor (AR)-negative and -positive prostate cancer PDX animal models, uptake was observed in both groups when the tumor reached a size of 50–300 mm³. The AR-negative group showed significantly higher [¹⁸F]FPIA uptake compared to the AR-positive group, with average tumor-to-muscle ratios of 1.6 and 1.2, respectively.</div></div><div><h3>Conclusions</h3><div>In summary, an optimized one-pot, two-step synthesis of [¹⁸F]FPIA on a vial-based automated synthesizer was successful and a seamless transition into a GMP facility is reported, enabling a streamlined transition to clinical production. Furthermore, we have demonstrated the use of [¹⁸F]FPIA for noninvasive metabolic imaging in prostate cancer and its potential to distinguish between different prostate cancer subtypes.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"154 ","pages":"Article 109605"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outside Back Cover - Graphical abstract TOC/TOC in double column/Cover image legend if applicable, Bar code, Abstracting and Indexing information","authors":"","doi":"10.1016/S0969-8051(26)00030-2","DOIUrl":"10.1016/S0969-8051(26)00030-2","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"154 ","pages":"Article 109631"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147849725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"H3RESCA chelator-enabled [18F]AlF labeling: An optimized temperature-resilient platform for PSMA-targeted PET tracers in prostate cancer","authors":"Yukai Zhang ,&nbsp;Zhoumi Hu ,&nbsp;Qingyu Zhang ,&nbsp;Bowu Zhang ,&nbsp;Jingye Li ,&nbsp;Jianjun Liu ,&nbsp;Cheng Wang","doi":"10.1016/j.nucmedbio.2026.109603","DOIUrl":"10.1016/j.nucmedbio.2026.109603","url":null,"abstract":"<div><div>Objective: Prostate-specific membrane antigen (PSMA) has emerged as a pivotal biomarker for the molecular imaging and targeted therapy of prostate cancer. To address the ongoing need for PSMA-targeting radiotracers with improved mild-labeling capability and reduced non-target organ exposure, beyond currently approved agents (e.g., [⁶⁸Ga]Ga-PSMA-11) that require higher temperatures or show hepatobiliary clearance, a novel ¹⁸F-labeled PSMA inhibitor, [¹⁸F]AlF-H₃RESCA-PSMA, was developed for PET imaging of prostate cancer.</div></div><div><h3>Methods</h3><div>H₃RESCA-PSMA was synthesized with an acyclic pentadentate chelator and radiolabeled with [¹⁸F]AlF at room temperature. Biodistribution and PET/CT studies were performed in PSMA-positive tumor xenografts, with [¹⁸F]AlF-PSMA-RESCA1 as comparator.</div></div><div><h3>Results</h3><div>Radiochemical yield was 75.5 ± 5.0%. [¹⁸F]AlF-H₃RESCA-PSMA showed 2-fold higher tumor uptake and slower wash-out versus PSMA-RESCA1, while exhibiting markedly reduced liver and kidney retention. PET images revealed superior tumor contrast and faster background clearance.</div></div><div><h3>Conclusions</h3><div>[¹⁸F]AlF-H₃RESCA-PSMA offers enhanced PSMA-targeting specificity and imaging contrast, supporting its clinical translation for prostate cancer PET.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"154 ","pages":"Article 109603"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro evaluation of anti-HIV radioimmunoconjugates labeled with astatine-211, thorium-227 and actinium-225","authors":"Anne-Sophie Kuhlmann ,&nbsp;Donald K. Hamlin ,&nbsp;Yawen Li ,&nbsp;Xinyi Wang ,&nbsp;Lily Li ,&nbsp;Chris Orvig ,&nbsp;Hans-Peter Kiem ,&nbsp;Brenda M. Sandmaier ,&nbsp;D. Scott Wilbur ,&nbsp;Seth Pincus ,&nbsp;Robert D. Harrington","doi":"10.1016/j.nucmedbio.2026.109602","DOIUrl":"10.1016/j.nucmedbio.2026.109602","url":null,"abstract":"<div><div>We conducted an <em>in vitro</em> investigation of the selective cytotoxicity of alpha-emitting radioimmunoconjugates (α-RICs) directed against cells expressing HIV envelope (Env) proteins. It is well known that monoclonal antibody (mAb)-targeted α-emitting radionuclides can effectively kill antigen-expressing cells; however, the expected low-level expression of HIV antigens on latently infected cells poses an obstacle to all anti-HIV immune-based treatments, including α-RICs. This investigation tested the cytotoxicity of the HIV envelope antigen-binding mAbs, PGT126 (binding gp120) and 7B2 (binding gp41), conjugated with labeling chelators that bind the α-emitters astatine-211 (²¹¹At), actinium-225 (²²⁵Ac) or thorium-227 (²²⁷Th).</div></div><div><h3>Methods</h3><div>High specific activity (SA) preparations of the α-RICs were made to increase the proportion of mAb conjugates carrying the α-emitting isotope. RIC cytolytic activity was evaluated against a cell line stably expressing the HIV envelope.</div></div><div><h3>Results</h3><div>²¹¹At-labeled mAb conjugates did not demonstrate specific cell killing, while the longer lived radiometal α-RICs, ²²⁷Th and ²²⁵Ac, efficiently and specifically killed HIV envelope expressing cells.</div></div><div><h3>Conclusions</h3><div>Potential explanations for these differential effects include the longer half-lives of ²²⁵Ac and ²²⁷Th compared to ²¹¹At and differences in the decay properties of radiometals compared to radiohalogens. These encouraging <em>in vitro</em> results suggest that <em>in vivo</em> evaluations of α-RIC in depleting the HIV harboring cells are warranted.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"154 ","pages":"Article 109602"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}