Nuclear medicine and biology最新文献

{"title":"Pharmacokinetics and dosimetry of radiolabeled FAP-targeting single-domain antibody 4AH29 in Göttingen minipigs","authors":"Nina Dumauthioz,&nbsp;Laurent Navarro,&nbsp;Marion Berdal,&nbsp;Surasa Nagachinta,&nbsp;Jos Eersels,&nbsp;Vaiva Gaspariunaite,&nbsp;Ana Rita Pombo Antunes,&nbsp;Jonatan Dewulf,&nbsp;Sam Massa,&nbsp;Troels Jørgensen,&nbsp;Lotte Kellemann Kristensen,&nbsp;Trine Starostka,&nbsp;Dimitrios Mantzilas,&nbsp;Tony Lahoutte,&nbsp;Matthias. D'Huyvetter","doi":"10.1016/j.nucmedbio.2026.109654","DOIUrl":"10.1016/j.nucmedbio.2026.109654","url":null,"abstract":"<div><h3>Background</h3><div>Fibroblast activation protein alpha (FAP) is a pan-tumor target highly expressed on cancer-associated fibroblasts. We developed 4AH29, a single-domain antibody binding FAP, and investigated the biodistribution of [¹³¹I]I-GMIB-4AH29 and [¹¹¹In]In-DOTA-4AH29 in Göttingen minipigs.</div></div><div><h3>Methods</h3><div>Following radiopharmaceutical administration, blood activity profile was determined by gamma-counter and biodistribution kinetics were determined using SPECT/CT imaging, respectively. The data obtained with [¹¹¹In]In-DOTA-4AH29 were used as a surrogate for its ¹⁷⁷Lu- and ²²⁵Ac-labeled analogues and extrapolation to human absorbed dose was calculated for all analogues.</div></div><div><h3>Results</h3><div>Radiolabeled 4AH29 showed good tolerability within the studied time frame. It displayed fast blood clearance driven by renal excretion. Kidney clearance dynamics of [¹³¹I]I-GMIB-4AH29 and [¹¹¹In]In-DOTA-4AH29 were distinct, likely driven by the different radiolabeling chemistry for halogen or metal conjugation. However, the contrasting patterns did not translate into relevant differences in mean residence time (MRT), nor was there a significant difference in bone marrow or liver MRTs when comparing halogen and metal-radiolabeled 4AH29. Extrapolated human absorbed doses for [¹³¹I]I-GMIB-4AH29 and [¹⁷⁷Lu]Lu-DOTA-4AH29 were compared given their similar particle decay and comparable physical half-lives. In kidneys, [¹³¹I]I-GMIB-4AH29 led to an extrapolated human absorbed dose of 8.23E-01 mGy/MBq, whereas [¹⁷⁷Lu]Lu-DOTA-4AH29 reached 5.86E-01 mGy/MBq. Consequently, the maximum tolerable administered activities were 28 and 39 GBq, respectively, to reach the renal absorbed dose limit of 23 Gy as determined by external beam radiation therapy (EBRT). In red marrow, the equivalent dose for [¹³¹I]I-GMIB-4AH29 was 3.8E-02 mGy/MBq and 1.36E-02 mGy/MBq with [¹⁷⁷Lu]Lu-DOTA-4AH29. Thus, 53 GBq and 148 GBq can be administered, respectively, before reaching the EBRT set absorbed dose threshold of 2 Gy.</div></div><div><h3>Conclusion</h3><div>4AH29 radiolabeled with ¹³¹I or ¹¹¹In is well tolerated in Göttingen minipigs within the studied time frame. Extrapolated dosimetry of radiolabeled 4AH29 using OLINDA software indicates that its administration within a clinically relevant range is possible without exceeding toxicity limits in critical organs.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"158 ","pages":"Article 109654"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148339376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","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)00071-5","DOIUrl":"10.1016/S0969-8051(26)00071-5","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"158 ","pages":"Article 109672"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148736178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced pre-therapy dosimetry for SSTR PET: A head-to-head preclinical assessment of [89Zr]Zr-DFO-TOC and [89Zr]Zr-DFO-TATE","authors":"Alexis M. Sanwick,&nbsp;Katherine N. Haugh,&nbsp;Dustin R. Osborne,&nbsp;John W. Dawson,&nbsp;Ivis F. Chaple","doi":"10.1016/j.nucmedbio.2026.109655","DOIUrl":"10.1016/j.nucmedbio.2026.109655","url":null,"abstract":"<div><div>Neuroendocrine tumors (NETs) represent a clinically heterogeneous group of malignancies originating from neuroendocrine cells, with the potential to arise in nearly any organ system. Despite their relatively low incidence, NETS are associated with significant morbidity and mortality, with reported 1- and 5-year mortality rate of 27.2% and 60.4%, respectively. These statistics underscore the critical importance of early and accurate diagnosis. A hallmark of NET biology is the overexpression of somatostatin receptors (SSTRs) on NET cell membranes. This molecular feature has been effectively exploited for both imaging and through the use of radiolabeled somatostatin analogues. To date, three FDA-approved radiopharmaceuticals for PET imaging of somatostatin receptor positive (SSTR+) NETs are clinically available, establishing PET as the standard imaging modality for disease detection, staging, and treatment planning of NETs. However, current tracers are limited by either the short half-lives or by practical constraints in production and distribution, restricting their broader clinical utility. ⁸⁹Zr (t_1/2 = 3.27 days, β⁺ = 22.3%, β⁺_avg = 395.5 keV) offers an attractive alternative, enabling imaging at extended timepoints with improved tumor-to-background contrast and the potential for more accurate pretherapy dosimetry. The aim of this work is to evaluate [⁸⁹Zr]Zr-DFO-TATE and [⁸⁹Zr]Zr-DFO-TOC for PET imaging of SSTR+ NETs. This study seeks to provide a comprehensive in vivo comparison of the two agents including the in vivo PET imaging, ex vivo biodistribution, and internal radiation dosimetry, with the overarching goal of advancing precision diagnostics and improving therapeutic planning for NET patients undergoing [¹⁷⁷Lu]Lu-DOTA-TATE therapy.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"158 ","pages":"Article 109655"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148361604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation of electroplated zinc-68 targets for gallium-68 cyclotron production using recovered zinc-68","authors":"Ian M. Horn,&nbsp;Mark S. Jacobson,&nbsp;Carter J. Jensen,&nbsp;Matthew D. Kiel,&nbsp;Jeffrey M. McEarchern","doi":"10.1016/j.nucmedbio.2026.109657","DOIUrl":"10.1016/j.nucmedbio.2026.109657","url":null,"abstract":"<div><h3>Background</h3><div>Gallium-68 (68Ga) is a PET isotope that is finding more use in the clinical setting as a PET diagnostic tool, for example 68Ga PSMA is widely used in the diagnosis of prostate cancer, and 68Ga dotatate for the diagnosis of neuroendocrine tumors. Current production is mostly performed using either 68Ge/68Ga generators or liquid targets containing 68Zn and irradiated with protons in an accelerator. Recently, GE Healthcare published an article describing the irradiation and purification of 68Ga using a solid 68Zn target. This article describes an electroplating process used to produce 68Zn targets.</div></div><div><h3>Method</h3><div>The method to produce 68Zn cyclotron targets for 68Ga production by electroplating zinc-68 onto a 1” diameter 99.99% natural silver planchette is described. Each target had differing plated masses, ranging from 40 to 170 mg using an electroplating solution produced from purified zinc-68 effluent from prior, non-solid target based 68Ga production processes. The targets were irradiated using a GE PET cyclotron proton beam with an energy of 16.5 MeV and beam current approximately 80 mA. Radiochemical yields of purified gallium-68 resulting from the dissolution of each target were measured using preliminary HPGe results to determine gallium-68 yield. The gallium-68-specific gamma emission at 1077.3 keV, as opposed to the indirect emission at 511 keV, was used to determine the amount of 68Ga present in the sample. In addition, the amount of stable metal contaminants (Zn, Fe, Ag and Al) were measured using qualitative ICP-OES.</div></div><div><h3>Results</h3><div>The targets produced using this technique were stable to both mild-mechanical abrasion (wipe with non-metallic material and washing with water) and irradiation by a 16.5 MeV cyclotron proton beam. Based on initial data, the optimum plating mass for 68Zn targets is between 60 mg and 160 mg. This applies to targets produced by this method and subsequently irradiated, digested, and purified using GE Healthcare equipment and protocols.</div></div><div><h3>Conclusion</h3><div>This article provides methodology to produce 68Zn solid targets for cyclotron production of 68Ga. The initial results from 68Ga specific quality control analytical techniques demonstrate the potential for establishing a GMP-compliant production process within an academic or hospital setting.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"158 ","pages":"Article 109657"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387825","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":"A new series of FAP inhibitors for cancer imaging based on 8-substituted (4-quinolinoyl)-glycyl-2-cyanopyrrolidine","authors":"Hanyue Ma,&nbsp;Le Li,&nbsp;Amber Piet,&nbsp;Maryana Handula,&nbsp;Corrina de Ridder,&nbsp;Debra Stuurman,&nbsp;Yann Seimbille","doi":"10.1016/j.nucmedbio.2026.109661","DOIUrl":"10.1016/j.nucmedbio.2026.109661","url":null,"abstract":"<div><div>Fibroblast activation protein (FAP) is highly expressed in cancer-associated fibroblasts across most epithelial tumors but FAP is nearly absent in normal tissues, making it an attractive target for cancer imaging and therapy. Small-molecule FAP inhibitors have emerged as potent imaging tracers due to their rapid tumor uptake and high tumor-to-background ratios (TBRs), although their short tumor residence limits therapeutic applications. To improve pharmacokinetics and expand theranostic potential, we developed a novel library of FAP inhibitors (eFAPs) based on an 8-quinoline-cyanopyrrolidine scaffold. Structural modifications were introduced by varying linker length between the pharmacophore and chelator, altering global charge, and modulating hydrophilicity. All eFAPs were highly hydrophilic (Log<em>D</em>_7.4: −3.2 to −3.7) and demonstrated strong inhibition of both human and murine FAP (IC₅₀, _{human FAP} &lt; 3 nM and IC₅₀, _{murine FAP} &lt; 4 nM, respectively), with high selectivity against prolyl oligopeptidase (PREP) and dipeptidyl peptidase-4 (DPP4). Radiolabeling with [¹¹¹In]In achieved &gt;96% radiochemical yield for the majority of the derivatives, with overall good stability in PBS and serums up to 24 h. In HT-1080.hFAP cells, eFAPs showed specific uptake (10.2 ± 1.9%–25.8 ± 4.5% AD), with eFAP-9 exhibiting the highest uptake, superior to the clinical reference FAPI-46 (17.5 ± 4.4% AD). <em>In vivo</em> SPECT/CT imaging revealed rapid blood clearance and tumor accumulation, resulting in clear tumor visualization sustained for up to 48 h for eFAP-12. Biodistribution confirmed strong tumor uptake of eFAP-9 (7.95 ± 3.68%ID/g), comparable to FAPI-46 (8.55 ± 1.28%ID/g) at 1 h p.i., and prolonged tumor half-life of eFAP-12 (6.01 h), which was 1.7-fold longer than FAPI-46 (2.84 h).</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"158 ","pages":"Article 109661"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated radiosynthesis of [64Cu]Cu-FAPI-2286 for FAP-targeted PET imaging","authors":"Mohd Faheem,&nbsp;Vaibhav Pandey,&nbsp;Nidhi Singh Kushwaha,&nbsp;Sanjay Gambhir,&nbsp;Manish Dixit","doi":"10.1016/j.nucmedbio.2026.109659","DOIUrl":"10.1016/j.nucmedbio.2026.109659","url":null,"abstract":"<div><h3>Background</h3><div>Fibroblast Activation Protein (FAP) is a critical target for imaging cancer-associated fibroblasts and active hepatic stellate cells in liver fibrosis. While FAPI-2286 has been widely explored with ⁶⁸Ga and ¹⁷⁷Lu, the use of copper-64 offers unique advantages for theranostics due to its amenable half-life and chemical pairing with therapeutic copper-67. This study focuses on the automated radiosynthesis of [⁶⁴Cu]Cu-FAPI-2286 in a green synthetic route, detailed physicochemical characterization, quality control analysis, and initial clinical evaluation of [⁶⁴Cu]Cu-FAPI-2286 in liver fibrosis.</div></div><div><h3>Methods</h3><div>The [⁶⁴Cu]Cu-FAPI-2286 was synthesized via manual and automated modules using aqueous solution of [⁶⁴Cu]CuCl₂. The reaction conditions (solvent, temperature, time) were optimized. Physicochemical evaluation included lipophilicity (logD_7.4) and stability challenges against EDTA, physiological media, and human serum. A pilot PET/CT scan was performed on a patient with HCV-related decompensated cirrhosis complicated by Grade III ascites to assess biodistribution and hepatic uptake.</div></div><div><h3>Results</h3><div>Optimized automated synthesis in aqueous medium at 40 °C yielded [⁶⁴Cu]Cu-FAPI-2286 with &gt;95% radiochemical purity and an apparent molar activity (AMA) of 258 ± 5 MBq/μmol. The radiotracer demonstrated high hydrophilicity with a logD_7.4 value of −2.38 ± 0.01. The complex exhibited excellent stability (&gt;95%) in serum and saline over 24 h and showed strong resistance to transchelation against a 500-fold excess of EDTA. Clinically, the patient with liver fibrosis demonstrated intense, diffuse hepatic uptake with a SUV_max(lbm) of 17.54, significantly higher than background, confirming active fibrogenesis.</div></div><div><h3>Conclusion</h3><div>We successfully established a robust, green, automated synthesis route for [⁶⁴Cu]Cu-FAPI-2286. The tracer's favorable hydrophilicity and stability make it a promising agent. The high uptake observed in the fibrotic liver highlights its potential as a non-invasive biomarker for staging liver fibrosis and for guiding future [⁶⁷Cu]Cu-FAPI-2286 therapies.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"158 ","pages":"Article 109659"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422839","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 vivo preclinical evaluation of YntraDose™ in pig's lung: A pilot study of a 90Y-microsphere device implantation","authors":"V. Lanni,&nbsp;A. Nocera,&nbsp;M.L. Vita,&nbsp;L. Lupoi,&nbsp;M.E. Caristo,&nbsp;S. Straino,&nbsp;F. Cianfarani,&nbsp;G. Bellavia,&nbsp;A. Capotosti,&nbsp;L. Indovina,&nbsp;R. Moretti,&nbsp;G. De Danieli,&nbsp;P. Bubba Bello,&nbsp;G. Bisaccioni,&nbsp;M.L. Calcagni,&nbsp;T. Scotognella","doi":"10.1016/j.nucmedbio.2026.109658","DOIUrl":"10.1016/j.nucmedbio.2026.109658","url":null,"abstract":"<div><h3>Background</h3><div>YntraDose™ is a novel injectable radiotherapeutic formulation combining BioGlue® (bovine serum albumin–glutaraldehyde polymer) with Yttrium-90 resin microspheres. This pilot preclinical feasibility study represents the first in vivo evaluation of YntraDose™ administration into lung tissue and was designed to assess its injectability, polymerization performance, biodistribution, dosimetry, and tissue response.</div></div><div><h3>Methods</h3><div>Seven healthy female Landrace pigs were enrolled and received ultrasound-guided percutaneous injections of YntraDose™ in two lung lobes (5 ml and 10 ml syringes targeting 150–185 MBq). Pigs were euthanized at 24 h, 7-, 14-, and 21 days post-injection for necropsy, PET/CT imaging, dosimetry, and histological evaluation. Immunohistochemistry for IL-1β, IL-6, and IL-8 was performed on lung biopsies to assess inflammatory activity.</div></div><div><h3>Results</h3><div>YntraDose™ administration was feasible and resulted in localized polymerization within the injection site, with no evidence of radioactivity spread to other organs. Histological analysis revealed areas of necrosis extending up to 1–1.5 cm from the main deposition site and diffuse inflammatory cell infiltration. IL-1β, IL-6, and IL-8–positive cells were identified throughout the tissue, indicating a strong inflammatory response.</div></div><div><h3>Conclusions</h3><div>This first in vivo preclinical investigation demonstrates that YntraDose™ can be successfully injected and polymerized in lung tissue, even at high radioactivity levels. Despite the intense inflammatory reaction observed, the results support further preclinical studies with optimized, clinically relevant ⁹⁰Y activities to evaluate the potential of YntraDose™ for localized lung tumor ablation.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"158 ","pages":"Article 109658"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NMB innovators series. Professor Michael R. Kilbourn, PhD: An enduring legacy of mentorship, scientific curiosity and research excellence","authors":"Peter J.H. Scott","doi":"10.1016/j.nucmedbio.2026.109660","DOIUrl":"10.1016/j.nucmedbio.2026.109660","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"158 ","pages":"Article 109660"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631047","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":"Carbonic anhydrase IX-targeted small molecule radiopharmaceuticals: A review of their role in clear cell renal cell carcinoma theranostics","authors":"Yuying Liu,&nbsp;Mengyi Zhang,&nbsp;Xinyue Ge,&nbsp;Xiangjun Meng","doi":"10.1016/j.nucmedbio.2026.109662","DOIUrl":"10.1016/j.nucmedbio.2026.109662","url":null,"abstract":"<div><h3>Background</h3><div>Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer subtype, representing 70–80% of cases. Its unique molecular profile and therapeutic resistance make it a key focus in oncology. Recent advances in targeting the ccRCC-specific biomarker carbonic anhydrase IX (CAIX), especially through radiolabeled small-molecule inhibitors, are revolutionizing its management.</div></div><div><h3>Methods</h3><div>We conducted a systematic literature search using PubMed, Web of Science, ACS, and CAS databases to identify promising small-molecule CAIX-targeted radiopharmaceuticals for ccRCC published between 2011 and early 2026.</div></div><div><h3>Results</h3><div>This review systematically outlines the biology and pathological role of CAIX in ccRCC, and surveys the landscape of CAIX-targeted radioligands under investigation—from acetazolamide and benzenesulfonamide to cyclic peptide-based probes. It also presents single-photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging results for selected promising candidates. We critically assess the current state and promise of theranostics, highlighting future directions and challenges. By summarizing key clinical findings, this work aims to inform the development of CAIX-targeted radiopharmaceuticals and to promote precision medicine in ccRCC.</div></div><div><h3>Conclusions</h3><div>[⁶⁸Ga]Ga-NY104, [^99mTc]Tc-PHC-102, [⁶⁸Ga]Ga-DPI-4452, [¹⁸F]F-VM4–037 and [¹⁸F]F-U-104 exhibit promising CAIX targeting. Structural optimization of these compounds holds promise for developing CAIX inhibitors with enhanced selectivity and lower toxicity for ccRCC therapy. At the clinical translation level, a series of novel probes represented by [⁶⁸Ga]Ga-NY104 and [⁶⁴Cu]Cu-PD-32766 have entered clinical investigation, enabling high-sensitivity and high-specificity detection of both primary and metastatic ccRCC lesions <em>via</em> PET/CT imaging. Moreover, theranostic platforms based on identical molecular scaffolds (<em>e.g.</em>, US2 platform, DPI-4452) have laid the foundation for a “see-and-treat” precision medicine paradigm.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"158 ","pages":"Article 109662"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605507","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":"Electroless semi-automatic synthesis of 225Ac-labeled PSMA-derivatives for clinical application and evaluation of rechelation capability","authors":"Marc Pretze,&nbsp;Petra Gehlmann,&nbsp;Florian Brandt,&nbsp;Constantin Mamat,&nbsp;Ralph A. Bundschuh","doi":"10.1016/j.nucmedbio.2026.109656","DOIUrl":"10.1016/j.nucmedbio.2026.109656","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Sustainable green radiochemistry is the result of current research, in which radiolabeling strategies are increasingly being developed in the direction of kit labeling. This includes the use of sunlight for reactions, but also tailor-made chelators allowing a to quantitative chelation of the corresponding radionuclide even at temperatures around 20 °C. The ultimate goal is to use these reaction conditions for labeling kit development in which only the radionuclide needs to be added and the reaction then occurs quantitatively in a sterile vial. Chelators such as HBED are already included in approved kits for the production of [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-PSMA-11 (Locametz®, IsoPROtrace11®, and Illuccix®) and allow radiolabeling at 20 °C. This paper reports on the semi-automatic labeling method of macropa(mcp)-based PSMA derivatives with &lt;sup&gt;225&lt;/sup&gt;Ac, which was performed at 20 °C without heating and, according to subsequent quality control, is technically ready-to-use for patient applications. To further strengthen the green aspect, critical chemicals like environmental persistent trifluoroacetic acid (TFA) were considered to be replace against more eco-friendly chemicals. Furthermore, additives like ascorbic acid or DTPA, which are usually used for protection against radiolysis or scavenge free progenies were considered to be eliminated from the process due to the reason, that the mcp-based precursor might be able to rechelate free progenies, as soon as they are generated from their parent nuclide &lt;sup&gt;225&lt;/sup&gt;Ac.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;An iQS module was equipped with sterile single-use components and an already automated radiolabeling process was adopted to the semi-automatic system. Three validation batches for two different mcp-based PSMA derivatives were produced including quality control with criteria fulfilling clinical standards.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Three consecutive validation batches were successfully produced for each mcp-M-PSMA and mcp-D-PSMA derivatives to evaluate the safety and robustness of the labeling method. Overall, the six batches reached radiochemical yields &gt;80% and hit the quality parameters such as radiochemical purity of &gt;95% for clinical application.&lt;/div&gt;&lt;div&gt;Additionally, the replacement of environmental persistent TFA of the HPLC eluents with phosphoric acid (H&lt;sub&gt;3&lt;/sub&gt;PO&lt;sub&gt;4&lt;/sub&gt;) led to similar retention times combined with a higher resolution in the radio-HPLC chromatograms.&lt;/div&gt;&lt;div&gt;The effect of rechelation was carefully evaluated using an excess amount of precursor. It was found that, with increasing concentration, a rechelation of free progenies occurred from 22 to 144 h. Either the reaction solution or the diluted product solution was analyzed by TLC and HPLC.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;The electroless synthesis of &lt;sup&gt;225&lt;/sup&gt;Ac-mcp-PSMA derivatives was successfully implemented to the iQS module, and the products fulfilled a","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"158 ","pages":"Article 109656"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}