Nuclear medicine and biology最新文献

{"title":"Enhancing the therapeutic index of [211At]YF2 with iodo pseudo carrier: A simple strategy for reducing accumulation in kidneys, salivary and lacrimal glands","authors":"Truc T. Huynh,&nbsp;Yutian Feng,&nbsp;Rebecca L. Banks,&nbsp;Ganesan Vaidyanathan,&nbsp;Michael R. Zalutsky","doi":"10.1016/j.nucmedbio.2025.109028","DOIUrl":"10.1016/j.nucmedbio.2025.109028","url":null,"abstract":"<div><h3>Introduction</h3><div>Low-molecular-weight (LMW) PSMA-targeted agents have enjoyed success; however, their off-target toxicity in normal tissues such as kidneys, salivary gland and lacrimal gland can be dose limiting. Herein, we have evaluated the effect of co-administration of the non-radioactive iodo pseudo carrier, iodo YF2, on the normal tissue uptake of [²¹¹At]YF2 in xenografted mice. The potential implications for clinical translation of these studies were investigated by evaluating the binding of LMW PSMA-targeted agents to murine and human PSMA.</div></div><div><h3>Methods</h3><div>[²¹¹At]YF2 was synthesized following established protocols. Groups of 5 mice bearing subcutaneous PSMA+ PC3 PIP xenografts received [²¹¹At]YF2 co-injected with varying i.v. doses of iodo YF2 (0–2 nmol), and the biodistribution was evaluated at 1 h post injection (p.i.). In another study, the biodistribution of [²¹¹At]YF2 alone and [²¹¹At]YF2 co-administered with 1.5 nmol iodo YF2 was evaluated at 1 and 8 h p.i. Bead-based radioligand binding assays were conducted for [¹³¹I]YF2 and several other LMW agents to compare their binding to human and murine PSMA.</div></div><div><h3>Results</h3><div>At 1 h, no significant difference was seen in kidney uptake of [²¹¹At]YF2 at iodo YF2 concentrations of 0, 0.05 and 0.1 nmol (<em>p</em> &gt; 0.05), but renal accumulations significantly reduced by co-administering 2.0 nmol iodo YF2 (<em>p</em> &lt; 0.0001). Decreases in salivary and lacrimal gland uptake also were observed at 1 h for [²¹¹At]YF2 co-injected with 0.1 nmol iodo YF2 (<em>p</em> &lt; 0.05). A follow-up study revealed a kidney uptake of 1.8 ± 0.4 % ID/g for [²¹¹At]YF2 with 1.5 nmol iodo YF2, compared to 46.5 ± 7.7 % ID/g for [²¹¹At]YF2 alone at 8 h. Tumor uptake showed no significant difference (<em>p</em> &gt; 0.05) between [²¹¹At]YF2 alone (17.1 ± 8.8 % ID/g at 1 h; 13.6 ± 5.3 % ID/g at 8 h) and [²¹¹At]YF2 plus 1.5 nmol iodo YF2 (12.8 ± 2.7 % ID/g at 1 h; 14.1 ± 3.2 % ID/g at 8 h). Bead-based radioligand binding assays showed that [¹³¹I]YF2 has the highest binding fractions to both human PSMA (94.1 ± 0.1 %) and murine PSMA (92.5 ± 0.2 %) with minimal differences between the two, while [¹⁷⁷Lu]PSMA-617 had the greatest species-dependent disparity with a binding fraction of 90.5 ± 0.3 % to human PSMA and 60.9 ± 1.4 % to murine PSMA.</div></div><div><h3>Conclusions</h3><div>Co-administration of iodo YF2 reduced kidney uptake of [²¹¹At]YF2 and decreased accumulation in normal tissues with no significant change in tumor uptake. In some cases, there was a significant difference in binding to human and murine PSMA among LMW PSMA-targeted agents suggesting that particularly for some agents, applying mouse data to predict human dosimetry must be done with caution.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"146 ","pages":"Article 109028"},"PeriodicalIF":3.6,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144084262","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":"Evaluation of radio-thin-layer chromatography as an alternative to radio-HPLC for [18F]SynVesT-1 metabolism analysis in rats","authors":"Tutukhanim Balayeva ,&nbsp;Ruth H. Asch ,&nbsp;Peng Wen Tan ,&nbsp;William Mennie ,&nbsp;Jie Tong ,&nbsp;Baosheng Chen ,&nbsp;Zhenwu Zhuang ,&nbsp;Chao Zheng ,&nbsp;MingQiang Zheng ,&nbsp;Takuya Toyonaga ,&nbsp;Zhengxin Cai","doi":"10.1016/j.nucmedbio.2025.109029","DOIUrl":"10.1016/j.nucmedbio.2025.109029","url":null,"abstract":"<div><h3>Purpose</h3><div>Alterations in synaptic vesicle glycoprotein 2A (SV2A) are linked to various neurodegenerative and neuropsychiatric disorders. Positron emission tomography (PET) imaging with radiotracers targeting SV2A, such as [¹⁸F]SynVesT-1, has proven effective for monitoring these changes. However, SV2A PET quantification using kinetic modeling requires radiometabolite analysis, which presents challenges, particularly in preclinical longitudinal studies due to the relatively large sample volume required by the standard radio-high-performance liquid chromatography (radio-HPLC) method. This study aimed to evaluate radio-thin layer chromatography combined with autoradiography (radio-TLC/AR) as an alternative to radio-HPLC in rat plasma radiometabolite analysis.</div></div><div><h3>Methods</h3><div>All rats received intravenous infusions of [¹⁸F]SynVesT-1. Arterial blood samples were collected at predetermined time points for up to 60 min post injection. [¹⁸F]SynVesT-1 radiometabolites in plasma and brain were assessed using both radio-HPLC and radio-TLC/AR.</div></div><div><h3>Results</h3><div>We observed a decline in [¹⁸F]SynVesT-1 plasma concentrations within the first 5 min post-injection. The parent fractions obtained by the radio-HPLC method significantly correlated with those obtained using radio-TLC/AR (R² = 0.99, <em>p</em> &lt; 0.0001). While radio-HPLC detected minimal radiometabolites in the brain (1.34 % ± 0.83 %, <em>n</em> = 4), these radiometabolites were not identifiable in selected brain regions using the radio-TLC/AR method (<em>n</em> = 1).</div></div><div><h3>Conclusion</h3><div>We were able to reliably evaluate the parent fractions of [¹⁸F]SynVesT-1 in plasma over a 60-min period using normal-phase radio-TLC/AR as an alternative to radio-HPLC. This approach requires less plasma and is less time-consuming with high reproducibility. Future studies will focus on applying this radio-TLC/AR method for metabolism correction of input functions, in the quantitative analysis of PET imaging data using kinetic modeling.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"146 ","pages":"Article 109029"},"PeriodicalIF":3.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071560","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(25)00049-6","DOIUrl":"10.1016/S0969-8051(25)00049-6","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"144 ","pages":"Article 109040"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255092","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":"Biodistribution and long-term toxicity of neutron-activated Samarium-153 oxide-loaded polystyrene microspheres in healthy rats","authors":"Hun Yee Tan ,&nbsp;Yin How Wong ,&nbsp;Azahari Kasbollah ,&nbsp;Mohammad Nazri Md Shah ,&nbsp;Basri Johan Jeet Abdullah ,&nbsp;Alan Christopher Perkins ,&nbsp;Chai Hong Yeong","doi":"10.1016/j.nucmedbio.2025.109026","DOIUrl":"10.1016/j.nucmedbio.2025.109026","url":null,"abstract":"<div><h3>Purpose</h3><div>Selective internal radiation therapy (SIRT) is an effective, minimally invasive treatment for intermediate and advanced-stage liver malignancies, particularly when other curative options are not viable. As an alternative to commercially available Yittrium-90 (⁹⁰Y) resin or glass microspheres, we have developed novel radiopharmaceutical, neutron-activated Samarium-153 oxide-loaded polystyrene ([¹⁵³Sm]Sm₂O₃-PS) microspheres for SIRT. The therapeutic efficacy of the formulation has been assessed in our previous study. This extended study aimed to evaluate the biodistribution and long-term toxicity of [¹⁵³Sm]Sm₂O₃-PS microspheres in a healthy Sprague-Dawley (SD) rat model.</div></div><div><h3>Methods</h3><div>Biodistribution was assessed in six healthy male SD rats following direct intrahepatic injection of radioactive [¹⁵³Sm]Sm₂O₃-PS microspheres. Static whole-body gamma imaging was performed at 1, 24, and 48 hour post-injection. Radioactivity levels in major organs were measured after euthanasia. For long-term toxicity evaluation, eighteen healthy male SD rats were divided into three groups and tested with: (1) decayed [¹⁵³Sm]Sm₂O₃-PS microspheres; (2) 4 % gelatin solution; and (3) untreated control. Over a 12-month period, body weight, body temperature and liver function biomarkers (ALT, AST, ALP and GGT) were monitored. Histopathological evaluations (HPE) of liver tissues were performed after the rats were sacrificed at the end of the study.</div></div><div><h3>Results</h3><div>The highest radioactivity (25.15 ± 2.32 % injected dose (ID)/g) was observed at the injected site in the liver at 48 h post-injection, with minimal or undetectable radioactivity in other organs, including spleen, bladder, kidneys, lungs, heart, bone, muscle, and blood. No significant changes (<em>p</em> &gt; 0.05) in body weight and body temperature were observed across groups, and no signs of systemic illness were noted in any of the rats. Liver function biomarkers remained within normal physiological ranges in all groups throughout the study. HPE revealed no lesions or severe inflammation in liver tissues across all groups.</div></div><div><h3>Conclusion</h3><div>[¹⁵³Sm]Sm₂O₃-PS microspheres demonstrated favourable biodistribution and no evidence of systemic or hepatic toxicity over a 12-month period in healthy rats. These findings support the safety profile of the microspheres and their feasibility for further preclinical and clinical trials.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"146 ","pages":"Article 109026"},"PeriodicalIF":3.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898925","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":"Application of [99mTc]Tc-GSA in the diagnosis of Staphylococcus aureus infections","authors":"Asuka Mizutani ,&nbsp;Ami Kondo ,&nbsp;Yuka Muranaka ,&nbsp;Yuma Momose ,&nbsp;Yuri Nishiyama ,&nbsp;Kakeru Sato ,&nbsp;Masato Kobayashi ,&nbsp;Keiichi Kawai","doi":"10.1016/j.nucmedbio.2025.109021","DOIUrl":"10.1016/j.nucmedbio.2025.109021","url":null,"abstract":"<div><h3>Introduction</h3><div><em>Staphylococcus aureus</em> can cause a variety of conditions such as bacteremia, sepsis, toxic shock syndrome, pneumonia, and infective endocarditis; therefore, a rapid and accurate diagnosis should be made to pinpoint the site of infection. This study aimed to use the existing nuclear medicine tracer [^99mTc]Tc-dimercaptosuccinic acid galactosyl human serum albumin ([^99mTc]Tc-GSA) as a simple technique for the early diagnosis of <em>S. aureus</em> infection.</div></div><div><h3>Methods</h3><div>The <em>in vitro</em> studies evaluated the accumulation of [^99mTc]Tc-GSA in <em>S. aureus</em>. In addition, the effect of metabolic and vital activity and inhibition of asialoglycoprotein receptors on [^99mTc]Tc-GSA accumulation were evaluated. <em>In vivo</em> studies were performed on the biodistribution and imaging of [^99mTc]Tc-GSA in the <em>S. aureus</em> SR3637 mouse thigh infection model.</div></div><div><h3>Results</h3><div><em>In vitro</em> studies have confirmed that [^99mTc]Tc-GSA accumulates to the same extent as 2-deoxy-2-[¹⁸F]fluoro-<span>d</span>-glucose, and it was thought that [^99mTc]Tc-GSA binds to the receptors that recognize the saccharide molecules and glycan chains expressed in <em>S. aureus</em>. In addition, in the distribution and imaging of [^99mTc]Tc-GSA, it was confirmed that the latter accumulates at the infection site and shows a clear contrast with the non-infected site.</div></div><div><h3>Conclusion</h3><div>The application of [^99mTc]Tc-GSA to the imaging diagnosis of <em>S. aureus</em> infection is expected to non-invasively detect the localization of <em>S. aureus</em> in real time, pinpoint the site of infection and determine the number of viable bacteria, and help in the selection of optimal therapeutic agents and treatments.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"146 ","pages":"Article 109021"},"PeriodicalIF":3.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886990","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":"Novel dibutyl ether resin for the purification of the Auger emitter antimony-119 from tin targets","authors":"Aivija Grundmane ,&nbsp;Caterina F. Ramogida ,&nbsp;Valery Radchenko","doi":"10.1016/j.nucmedbio.2025.109022","DOIUrl":"10.1016/j.nucmedbio.2025.109022","url":null,"abstract":"<div><div>Antimony-119 (¹¹⁹Sb, t_1/2 = 38.19 h) is an Auger electron emitting radionuclide of interest for radiopharmaceutical therapy (RPT). The potential of ¹¹⁹Sb has only been explored theoretically, due to the absence of a suitable bifunctional chelator that enables the attachment of the radionuclide onto a radiopharmaceutical. Meanwhile, potential chelators are difficult to evaluate given that the production and radiochemical purification of ¹¹⁹Sb has not been optimized for radiopharmaceutical applications. ¹¹⁹Sb can be produced from proton bombardment of tin-119 (¹¹⁹Sn) targets on medical cyclotrons, subsequently the nanograms of radioantimony must be efficiently separated from the macroscopic (&gt; mg) amount of target material while being recovered in a matrix suitable for chelation. To this end, a solid phase extraction (SPE) method employing a novel dibutyl ether (DBE) resin was developed to separate radioantimony from tin targets. The DBE resin was synthesized and characterized using thermogravimetric analysis, total organic carbon, and ¹H nuclear magnetic resonance spectroscopy. The DBE resin exhibited excellent capacity (&gt;8 mg Sb per gram) and integrity. Distribution coefficients (K_D) for Sb(V) (K_D up to 4600) and Sn(IV) (K_D &lt;0.3) showed good separation (Separation factor of &gt;15,000) of both elements at high concentrations of HCl. Finally, dynamic separations with the DBE resin were capable of recovering up to 79 ± 2 % of radioantimony (^1xxSb(III)) in 2 mL of 0.5 M sodium thioglycolate solution when separating nanogram quantities of ^1xxSb from tens of milligrams of stable tin. Quantitative recovery of Sn was also achieved in just 1.5 mL of concentrated hydrochloric acid, indicating the potential for target recycling of enriched ¹¹⁹Sn required for pre-clinical evaluation of ¹¹⁹Sb.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"146 ","pages":"Article 109022"},"PeriodicalIF":3.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870092","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":"Nicotinic acetylcholine receptor imaging with [18F]ASEM for skeletal muscle denervation: A novel assessment for peripheral neuromuscular disorders","authors":"Jae Sung Park ,&nbsp;Jin Hwa Jung ,&nbsp;Seog-Young Kim ,&nbsp;Nare Ko ,&nbsp;Sang Ju Lee ,&nbsp;Seung Jun Oh ,&nbsp;Jin-Sook Ryu ,&nbsp;Da Bin Ko ,&nbsp;Won Kim ,&nbsp;Kyunggon Kim ,&nbsp;Yong-il Kim ,&nbsp;Seung Hak Lee","doi":"10.1016/j.nucmedbio.2025.109023","DOIUrl":"10.1016/j.nucmedbio.2025.109023","url":null,"abstract":"<div><h3>Purpose</h3><div>Despite its invasive and subjective nature, needle electromyography (nEMG) remains a standard method for evaluating peripheral nerve injuries. Increased alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR) expression has been observed in an animal nerve injury model of muscle denervation. Hence, we used [¹⁸F]ASEM positron emission tomography (PET) to investigate the temporal characteristics of alpha7-nAChR expression following skeletal muscle denervation, and tested the correlation between nerve injury severity and [¹⁸F]ASEM PET uptake intensity.</div></div><div><h3>Methods</h3><div>We established a sciatic nerve injury rat model of skeletal muscle denervation. First, [¹⁸F]ASEM PET and nEMG were conducted simultaneously in the complete nerve injury models over time. Next, we used a partial nerve injury model to establish signal intensity as a function of nerve injury severity. Maximum standardized uptake value (SUVmax) and lesion-to-normal ratio (LNR) were used to semi-quantitatively represent [¹⁸F]ASEM uptake.</div></div><div><h3>Results</h3><div>Increased [¹⁸F]ASEM uptake began 1 day after denervation (SUVmax, denervation, 1.00 ± 0.32; SUVmax, control, 0.62 ± 0.23; <em>P</em> &lt; 0.05; <em>n</em> = 7) and lasted to the final 12-week time point. LNR also increased 1 day after denervation, detecting earlier changes compared to nEMG. The signal intensity of [¹⁸F]ASEM uptake in denervated skeletal muscle was significantly associated with nerve injury severity (Spearman correlation coefficient between SUVmax and nerve injury severity = 0.82; Spearman correlation coefficient between LNR and nerve injury severity = 0.75; both <em>P</em> &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>[¹⁸F]ASEM PET targeting the alpha7-nAChR can be used to assess effects of skeletal muscle denervation. This molecular imaging modality holds potential for early assessment of peripheral nerve injury and may also facilitate the evaluation of the injury severity.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"146 ","pages":"Article 109023"},"PeriodicalIF":3.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874154","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":"Adaptation of a commercially available module for the production of alpha-[11C]methyl-L-tryptophan ([11C]AMT) for human use","authors":"Karsten Bamminger ,&nbsp;Cécile Philippe ,&nbsp;Natalie Schindler ,&nbsp;Verena Pichler ,&nbsp;Lukas Nics ,&nbsp;Wolfgang Wadsak ,&nbsp;Andreas Hahn ,&nbsp;Rupert Lanzenberger ,&nbsp;Marcus Hacker ,&nbsp;Chrysoula Vraka","doi":"10.1016/j.nucmedbio.2025.109020","DOIUrl":"10.1016/j.nucmedbio.2025.109020","url":null,"abstract":"<div><div>The complex radiosynthesis of alpha-[¹¹C]methyl-L-tryptophan ([¹¹C]AMT) involves harsh chemicals and conditions, posing challenges for its implementation on commercially available synthesis modules. This study describes the adaptation of the GE TRACERlab FX2 C module for [¹¹C]AMT production using both a half-manual approach and a semi-automated method incorporating a 16-way valve system.</div><div>[¹¹C]AMT was synthesized with decay-corrected radiochemical yields of 13 ± 7.5 % (half-manual) and 10.4 ± 4.1 % (semi-automated), with radiochemical purities exceeding 95 %. The half-manual approach demonstrated higher reliability in synthesis success but required increased operator intervention, while the semi-automated method minimized radiation exposure to the operator. Key factors influencing synthesis success included the preparation and precise addition of lithium diisopropylamide and the use of a soda lime column to mitigate iodine contamination during [¹¹C]CH₃I transfer.</div><div>This work presents a practical and scalable solution for producing [¹¹C]AMT on a commercially available module, enabling its broader application in clinical research, particularly in brain imaging and pediatric oncology.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"146 ","pages":"Article 109020"},"PeriodicalIF":3.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881797","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":"Biodistribution of [18F]BCPP-BF in humans: a first-in-human positron emission tomography study","authors":"Kengo Sato ,&nbsp;Tomoyasu Bunai ,&nbsp;Akinori Oda ,&nbsp;Hiroyuki Ohba ,&nbsp;Yoshitaka Sano ,&nbsp;Aoi Tokui ,&nbsp;Hideo Tsukada ,&nbsp;Sadahiko Nishizawa ,&nbsp;Norihiro Harada ,&nbsp;Yasuomi Ouchi","doi":"10.1016/j.nucmedbio.2025.109019","DOIUrl":"10.1016/j.nucmedbio.2025.109019","url":null,"abstract":"<div><h3>Introduction</h3><div>[¹⁸F]BCPP-BF and [¹⁸F]BCPP-EF are PET probes used to evaluate mitochondrial function by targeting MC-I. Clinical studies on [¹⁸F]BCPP-EF have been reported, particularly brain studies. However, no reports exist on the use of [¹⁸F]BCPP-BF in humans. Therefore, in this study, we aimed to apply [¹⁸F]BCPP-BF to humans for the first time to assess its safety and radiation dose. We also aimed to explore the whole-body distribution of both probes by comparing the data acquired from the same participants.</div></div><div><h3>Methods</h3><div>Ten healthy participants underwent whole-body PET/CT measurements of [¹⁸F]BCPP-BF (117.0–153.8 MBq/body) for 90 min. Approximately 2–3 weeks after the measurements, the participants underwent [¹⁸F]BCPP-EF (109.2–158.8 MBq/body) measurements. Thirteen volumes of interest (VOIs) were manually drawn on the brain and peripheral organs using PET/CT images to evaluate the distribution and kinetics of the probes. The equivalent dose for each organ and the whole-body effective dose for each participant were calculated according to the Medical Internal Radiation Dose schema using OLINDA/EXM software.</div></div><div><h3>Results</h3><div>The highest radiation doses from the administration of [¹⁸F]BCPP-BF were observed in the small intestine (65.5 ± 8.7 μGy/MBq), and the estimated effective dose (16.3 ± 2.3 μSv/MBq) was well-tolerated. There were no clinically significant safety concerns. A high accumulation of [¹⁸F]BCPP-BF was observed in the kidney, pancreas, and heart, consistent with the findings in previously reported animal studies. The distributions of both tracers were similar. However, the kinetics of [¹⁸F]BCPP-BF were different, with higher uptake and slower washout in the kidney and pancreas, and lower uptake and slower washout in the brain and liver, from those of [¹⁸F]BCPP-EF.</div></div><div><h3>Conclusion</h3><div>[¹⁸F]BCPP-BF is safe and acceptable for clinical use owing to its low toxicity and radiation dose. [¹⁸F]BCPP-BF and [¹⁸F]BCPP-EF generally exhibited similar whole-body distributions; however, their organ-specific kinetics differed slightly. The appropriate selection of these probes can provide a more accurate assessment of human mitochondrial function.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"144 ","pages":"Article 109019"},"PeriodicalIF":3.6,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844476","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":"Affinity maturation and optimization of CD44v6-targeting antibodies for molecular radiotherapy","authors":"Anja Charlotte Lundgren Mortensen ,&nbsp;Camilla Hofström ,&nbsp;Helena Persson ,&nbsp;Leif Dahllund ,&nbsp;Fredrik Y. Frejd ,&nbsp;Marika Nestor","doi":"10.1016/j.nucmedbio.2025.109012","DOIUrl":"10.1016/j.nucmedbio.2025.109012","url":null,"abstract":"<div><h3>Aim</h3><div>This study aimed to improve the efficacy of the CD44v6-targeting antibody UU-40 for molecular radiotherapy through affinity maturation and IgG subclass optimization.</div></div><div><h3>M&amp;M</h3><div>A panel of affinity-matured antibody candidates was generated and characterized as both human IgG4 and IgG1 with LALA mutations. Surface plasmon resonance and LigandTracer analyses identified several candidates with superior affinity and off-rates compared to the parental UU-40. Biodistribution studies in xenograft models using Lutetium-177 (¹⁷⁷Lu)-labeled antibodies showed improved tumor retention for selected candidates, particularly UU-A-155. Species cross-reactivity assays confirmed binding to cynomolgus and rabbit v6-peptides, supporting future toxicity studies.</div></div><div><h3>Results</h3><div>The IgG1 LALA format demonstrated reduced binding to Fcγ receptors, potentially improving the safety profile. UU-A-155 emerged as the lead candidate for clinical translation, showing superior performance in both affinity and tumor retention. Our findings highlight the importance of comprehensive <em>in vitro</em> and <em>in vivo</em> assessments in antibody development, and provides valuable insights into optimizing antibody-based molecular radiotherapy.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"144 ","pages":"Article 109012"},"PeriodicalIF":3.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850671","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}