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A high-affinity anti-BCMA nanobody was radiolabeled for PET imaging using [18F]FPy-pyridine and for radioligand therapy using [131I]I. Target expression, binding affinity, and specificity were evaluated in vitro, followed by PET studies in xenografts and systemic MM models in NSG mice. Therapeutic testing used fractionated [131I]I-BCMA-Nb regimens, assessing tumor burden, toxicity, and histopathology. Results showed rapid clearance, high tumor-to-background ratios, dose-dependent regression, and complete remission at 18.5 MBq with minimal systemic toxicity, supporting clinical translation.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/precision-radiolabeled-b-cell-maturation-nanobody-for-targeted-pet-imaging-and-radioligand-therapy-of-disseminated-multiple-myeloma/453529/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/precision-radiolabeled-b-cell-maturation-nanobody-for-targeted-pet-imaging-and-radioligand-therapy-of-disseminated-multiple-myeloma/453529.png","ImageObject",300,407,{"name":92,"@type":93},"Miles","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What nanobody target and imaging/therapy labels were used in the study?","Question",{"text":112,"@type":113},"The study used an anti-BCMA nanobody. It was labeled with [18F]FPy-pyridine for PET imaging and with [131I]I for radioligand therapy.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was PET imaging performance evaluated in preclinical models?",{"text":117,"@type":113},"PET imaging was performed in subcutaneous MC38-human BCMA xenografts and systemic MM models (H929 and RPMI8226) in NSG mice, assessing tracer uptake in BCMA-positive lesions versus controls.",{"name":119,"@type":110,"acceptedAnswer":120},"What did the therapy experiments show about tumor control and safety?",{"text":121,"@type":113},"Fractionated [131I]I-BCMA-Nb treatments produced dose-dependent tumor regression, with 100% complete remission at 18.5 MBq in treated mice. Toxicity assessments indicated minimal systemic toxicity with restored hematopoiesis and reduced BCMA expression and proliferation markers.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},453529,1790769875,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":36,"preview_page_count":4},13056703019404,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Theranostics 2026, Vol. 16, Issue 6 2748  \nIvyspring  \nInternational Publisher  \nTheranostics  \n2026; 16(6): 2748-2763. doi: 10.7150/thno.126920  \nResearch Paper  \nPrecision radiolabeled B-cell maturation nanobody for targeted PET imaging and radioligand therapy of disseminated multiple myeloma  \nBehnaz Ghaemi1, Colleen P. Olkowski1, Falguni Basuli2, Jianfeng Shi2, Ryan Young3, Dickran Kazandjian4, Ola Landgren4, Elizabeth Hill3, Peter L. Choyke1, Orit Jacobson1􀀍  \n1. Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, 20892, USA.  \n2. Chemistry and Synthesis Center, National Heart, Lung, and Blood Institute, NIH, Rockville, Maryland, 20850, USA.  \n3. Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, 20892, USA.  \n4. Sylvester Myeloma Institute, Sylvester Comprehensive Cancer Center, Department of Medicine, Myeloma Division University of Miami, Florida, 33146, USA.  \n􀀍 Corresponding author: Orit Jacobson, email: [orit.jacobsonweiss@nih.gov](orit.jacobsonweiss@nih.gov).  \n© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [https://ivyspring.com/terms](https://ivyspring.com/terms) for full terms and conditions.  \nReceived: 2025.10.18; Accepted: 2025.12.08; Published: 2026.01.01  \nAbstract  \nBackground: Multiple myeloma (MM) is an incurable plasma cell malignancy with limited disease-specific imaging options. Current diagnostic methods often fail to detect early disease states and minimal residual disease, highlighting the need for more precise molecular imaging and targeted therapeutic approaches. We developed a radiolabeled nanobody targeting B-cell maturation antigen (BCMA) to enable both high-contrast molecular imaging and targeted radioligand therapy in human MM models.  \nMethods: A high-affinity anti-BCMA nanobody was labeled with [ 18 F]FPy-pyridine prosthetic group for PET imaging and [131 I]I for radioligand therapy. Target expression and in vitro binding affinity and specificity were assessed using biolayer interferometry, flow cytometry, and cell-based assays. PET imaging studies were performed in subcutaneous MC38-human BCMA xenografts and systemic human MM models (H929 and RPMI8226 cell lines) administered intravenously in NSG mice. Therapeutic efficacy was evaluated using a fractionated treatment regimen with [ 131 I]I-BCMA-Nb (four weekly injections of 7.4 or 18.5 MBq), monitoring tumor burden via bioluminescence imaging and [ 18 F]FDG-PET. Toxicity assessment included body weight monitoring, complete blood counts, biochemical analyses, and histopathological examination.  \nResults: [ 18 F]FPy-BCMA-Nb demonstrated high binding affinity and excellent tumor specificity with rapid systemic clearance. PET imaging showed significantly higher uptake in BCMA-positive lesions (6–8% ID/g) compared to controls (1% ID/g), with minimal kidney retention (\u003C1% ID/g by 3 h). In systemic MM models, the tracer specifically targeted bone marrow lesions with high tumor-to-background ratios. Therapeutic studies revealed dose-dependent tumor regression, with the 18.5 MBq [131 I]I-BCMA-Nb regimen achieving 100% complete remission in treated mice. Biochemical and histopathological analyses confirmed minimal systemic toxicity, restoration of normal hematopoiesis, and significant reduction in BCMA expression and proliferation markers post-treatment.  \nConclusion: This BCMA-targeted nanobody platform offers a promising theranostic approach for precise detection and treatment of disseminated multiple myeloma. The combination of exceptional tumor specificity, minimal off-target accumulation, rapid clearance, and potent therapeutic efficacy, along with a favorable safety profile, supports its potential for clinical translation in MM diagnosis and therapy.  \nKeywords: ","cbCaildz2IgcypEq","https://ap.wps.com/l/cbCaildz2IgcypEq","pdf",5661228,16,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusion\n# Introduction","[{\"question\":\"What nanobody target and imaging/therapy labels were used in the study?\",\"answer\":\"The study used an anti-BCMA nanobody. It was labeled with [18F]FPy-pyridine for PET imaging and with [131I]I for radioligand therapy.\"},{\"question\":\"How was PET imaging performance evaluated in preclinical models?\",\"answer\":\"PET imaging was performed in subcutaneous MC38-human BCMA xenografts and systemic MM models (H929 and RPMI8226) in NSG mice, assessing tracer uptake in BCMA-positive lesions versus controls.\"},{\"question\":\"What did the therapy experiments show about tumor control and safety?\",\"answer\":\"Fractionated [131I]I-BCMA-Nb treatments produced dose-dependent tumor regression, with 100% complete remission at 18.5 MBq in treated mice. Toxicity assessments indicated minimal systemic toxicity with restored hematopoiesis and reduced BCMA expression and proliferation markers.\"}]","Precision radiolabeled B-cell maturation nanobody for targeted PET imaging and radioligand therapy of disseminated multiple myeloma | PDF",1790739044]