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Results show radionuclide-dependent bystander toxicity, dose-dependent survival changes, and ROS/apoptosis-necrosis patterns that support optimizing therapy by emitter energy profile.",{"@graph":14,"@context":77},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/assessing-the-radiation-induced-bystander-effect-in-radionuclide-therapy-using-targeted-radiopharmaceuticals/405820/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/assessing-the-radiation-induced-bystander-effect-in-radionuclide-therapy-using-targeted-radiopharmaceuticals/405820.png","ImageObject",300,407,{"name":42,"@type":43},"River Wang","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-03","2026-09-28",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69,73],{"name":60,"@type":61,"acceptedAnswer":62},"What radiation-induced bystander effect (RIBBE) question does this study address in radionuclide therapy?","Question",{"text":63,"@type":64},"It investigates whether bystander effects occur in radionuclide therapy and how their magnitude and characteristics depend on the radionuclide used.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Which radiopharmaceutical targeting approach and cell model are used?",{"text":68,"@type":64},"Trastuzumab antibody targeting HER2 is labeled with radionuclides (Y-90, Lu-177, I-125) and tested in HER2-overexpressing cell lines, using a media-transfer protocol to evaluate direct and bystander effects.",{"name":70,"@type":61,"acceptedAnswer":71},"How do Y-90, Lu-177, and I-125 compare in bystander toxicity and cellular outcomes?",{"text":72,"@type":64},"Bystander induced reductions in clonogenic survival are observed for all formulations, with dose-dependent survival differences where 90Y and 177Lu show greater bystander toxicity than 125I. Higher doses of 90Y/177Lu produce more apoptosis and necrosis, while 125I shows lower cytotoxicity; ROS generation follows a similar pattern.",{"name":74,"@type":61,"acceptedAnswer":75},"What is the key conclusion regarding optimizing radionuclide-based cancer therapy?",{"text":76,"@type":64},"Therapeutic efficacy and cellular response depend on the specific radionuclide and its energy profile, so further exploration of RIBBEs is needed to optimize radionuclide cancer therapies and improve clinical effectiveness.","https://schema.org",{"og:url":32,"og:type":79,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":81,"canonical":32},"index,follow",{"doc_id":83,"site_id":7},405820,1790816167,{"code":4,"msg":86,"data":87},"success",[88,92,96,100,105,110,114,119,123,126,130],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},"Exam",70,"exam",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},5,"Comic",60,"comic",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},6,"Technology",50,"technology",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},7,40,"healthcare",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},8,"Research & Report",30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":121,"slug":122},"Religion & Spirituality",20,"religion-spirituality",{"id":121,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":121,"slug":125},"World Cup","world-cup",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":127,"slug":129},10,"Lifestyle","lifestyle",{"id":131,"doc_module":4,"doc_module_name":25,"category_name":132,"show_sort_weight":101,"slug":133},19,"General","general",{"code":4,"msg":86,"data":135},{"doc_id":83,"user_id":136,"nickname":42,"user_avatar":137,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":143,"language":144,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":145,"faqs":146,"seo_title":147,"seo_description":12,"update_tm":148,"read_time":112,"preview_page_count":4},1099514067438,"https://ap-avatar.wpscdn.com/avatar/100002539ee87300030?x-image-process=image/resize,m_fixed,w_180,h_180&k=1780474512215547542","Sharma et al. EJNMMI Radiopharmacy and Chemistry (2025) 10:83  \n[https://doi.org/10.1186/s41181-025-00393-0](https://doi.org/10.1186/s41181-025-00393-0)  \nEJNMMI Radiopharmacy and Chemistry  \nRESEARCH ARTICLE Open Access  \nAssessing the radiation-induced bystander  effect in radionuclide therapy using targeted radiopharmaceuticals  \nRohit Sharma 1, Archana Mukherjee 1,3*, Poonam Jagasia2 and Suman Kumar Singh2  \n*Correspondence:  \nArchana Mukherjee[archanas@barc.gov.in](archanas@barc.gov.in)[ ](archanas@barc.gov.in)1Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400094, India  \n2Fuel Reprocessing Division, Bhabha Atomic Research Centre, Mumbai 400094, India  \n3Homi Bhabha National Institute, Anushaktinagar, Mumbai 400085, India  \nAbstract  \nBackground Radiation-induced biologic bystander effects (RIBBEs) where nonirradiated cells display radiation like responses are well established in the context of external beam radiotherapy. However, their presence and characteristics in radionuclide therapy have been explored in only a limited number of studies. With the growing application of radionuclide therapy, this study was designed to investigate RIBBEs using a targeting agent labeled with three different types of emitters, aiming to quantify the varying biological effects attributable to each radionuclide and to devise strategies for achieving maximum therapeutic effect.Trastuzumab antibody targeting human epidermal growth factor receptor 2 (HER2) was labeled with radionuclides of varying energy profile; Y-90 (β − emitter), Lu-177 (β −/γ-emitter), and I-125 (Auger electron emitter). The radiolabeled conjugates were characterized, and their specificity was evaluated. Studies to evaluate both direct and bystander effects in (HER2) receptor overexpressing cell lines were performed via a media transfer protocol.  \nResults The study highlights distinct cellular responses depending on the radionuclide employed, with significant bystander induced reductions in clonogenic survival observed for all radiolabeled formulations. Notably, HER2-overexpressing  \nSK-OV-3 and SK-BR-3 cells displayed dose-dependent variations in survival, with 90Y and 177 Lu demonstrating greater bystander toxicity than 125 I. The survival fraction of recipient cells, which were exposed solely to media containing bystander factors, decreased significantly, indicating the potency of bystander factors in influencing therapeutic outcomes. Additionally, cytotoxicity assays revealed that higher doses of 90Y and 177 Lu induced substantial apoptosis and necrosis, whereas 125 I exhibited lower cytotoxicity, consistent with its lower energy emission profile. Reactive oxygen species (ROS) generation assays corroborated these findings, showing elevated ROS levels indirect and donor cell groups treated with 90Y and 177 Lu, while recipient cells exhibited relatively lower ROS induction.  \nConclusions This study elucidates the complex interplay of direct and bystander effects in targeted radionuclide therapy, demonstrating that the therapeutic efficacy and cellular response depend on the specific radionuclide and its energy profile. The findings emphasize the need for further exploration of RIBBEs to optimize radionuclidebased cancer therapies to enhance their clinical efficacy.  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in ","cbCaitIjLgwrQFZP","https://ap.wps.com/l/cbCaitIjLgwrQFZP","pdf",2313658,16,"English","# Abstract\n# Introduction\n# Targeted radionuclide therapy (TRT)\n# Results and discussion\n# Conclusions","[{\"question\":\"What radiation-induced bystander effect (RIBBE) question does this study address in radionuclide therapy?\",\"answer\":\"It investigates whether bystander effects occur in radionuclide therapy and how their magnitude and characteristics depend on the radionuclide used.\"},{\"question\":\"Which radiopharmaceutical targeting approach and cell model are used?\",\"answer\":\"Trastuzumab antibody targeting HER2 is labeled with radionuclides (Y-90, Lu-177, I-125) and tested in HER2-overexpressing cell lines, using a media-transfer protocol to evaluate direct and bystander effects.\"},{\"question\":\"How do Y-90, Lu-177, and I-125 compare in bystander toxicity and cellular outcomes?\",\"answer\":\"Bystander induced reductions in clonogenic survival are observed for all formulations, with dose-dependent survival differences where 90Y and 177Lu show greater bystander toxicity than 125I. Higher doses of 90Y/177Lu produce more apoptosis and necrosis, while 125I shows lower cytotoxicity; ROS generation follows a similar pattern.\"},{\"question\":\"What is the key conclusion regarding optimizing radionuclide-based cancer therapy?\",\"answer\":\"Therapeutic efficacy and cellular response depend on the specific radionuclide and its energy profile, so further exploration of RIBBEs is needed to optimize radionuclide cancer therapies and improve clinical effectiveness.\"}]","Assessing the radiation-induced bystander effect in radionuclide therapy using targeted radiopharmaceuticals | PDF",1790561950]