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This study develops and evaluates a CTS-B activity-based multimodality theranostic agent for cancer imaging and treatment. The CTS-B probe BMX2 was synthesized and labeled with 68Ga and 90Y to generate 68Ga-BMX2 for multimodality imaging and 90Y-BMX2 for radiotherapy. Binding was assessed with fluorescent western blots, confocal imaging, and cell uptake studies using multiple cancer cell lines, with CA074 as a control inhibitor. In vivo PET and fluorescence imaging on HeLa xenografts showed high tumor uptake over 24 h, and 90Y-BMX2 significantly inhibited tumor growth, supporting potential 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/radioactive-and-fluorescent-dual-modality-cysteine-cathepsin-b-activity-based-probe-for-cancer-theranostics/382566/",{"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/radioactive-and-fluorescent-dual-modality-cysteine-cathepsin-b-activity-based-probe-for-cancer-theranostics/382566.png","ImageObject",300,407,{"name":92,"@type":93},"\tCallum ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main goal of developing BMX2 in this study?","Question",{"text":112,"@type":113},"To create and evaluate a CTS-B activity-based multimodality theranostic probe for both cancer imaging and radiotherapy.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were 68Ga and 90Y used in the dual-modality approach?",{"text":117,"@type":113},"BMX2 was labeled with 68Ga to enable multimodality imaging (including PET) and with 90Y to enable radiation therapy.",{"name":119,"@type":110,"acceptedAnswer":120},"What evidence supports BMX2 specificity and activation by CTS-B?",{"text":121,"@type":113},"Fluorescent western blots using recombinant active human CTS-B and control conditions with the CTS-B inhibitor CA074 showed that BMX2 binding and activation depend on the enzyme environment and conditions, alongside imaging and uptake measurements.","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},382566,1790834580,{"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":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},137451211410,"https://ap-avatar.wpscdn.com/avatar/2000bb0a9246f588df?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786362646172706240","[pubs.acs.org/molecularpharmaceutics](pubs.acs.org/molecularpharmaceutics)  Article   \nRadioactive and Fluorescent Dual Modality Cysteine Cathepsin B Activity-Based Probe for Cancer Theranostics  \nLianbo Zhou,§ Feng He,§ Xin Xiang, Chuning Dong, Tian Xiang, Xian Li, Hong Li, Lihong Bu, Yunhua Wang, and Xiaowei Ma*  \n Cite This: Mol. Pharmaceutics 2023, 20, 3539−3548  \nRead Online  \n\n|  |  |  |  |  |  |\n| --- | --- | --- | --- | --- | --- |\n| ACCESS   | Metrics & More |  |  Article Recommendations |  | *sı Supporting Information |\n\nABSTRACT: Cysteine cathepsin B (CTS-B) is a crucial enzyme that is overexpressed in numerous malignancies and contributes to the invasion and metastasis of cancer. Therefore, this study sets out to develop and evaluate an activity-based multimodality theranostic agent targeting CTS-B for cancer imaging and therapy. A CTS-B activity-based probe, BMX2, was synthesized and labeled efficiently with 68Ga and 90Y to produce 68Ga-BMX2 for multimodality imaging and 90Y-BMX2 for radiation therapy. The affinity and specificity of BMX2 binding with the CTS-B enzyme were determined by fluorescent western blots using recombined active human CTS-B enzyme (rh-CTS-B) and four cancer cell lines including HeLa, HepG2, MCF7, and U87MG, with CA074 as  \nthe CTS-B inhibitor for control. Confocal laser scanning microscope imaging and cell uptake measurement were also performed. Then, in vivo PET imaging and fluorescence imaging were acquired on HeLa xenografts. Finally, the therapeutic effect of 90Y-BMX2 was tested. BMX2 could be specifically activated by rh-CTS-B and stably bound to the enzyme. The binding of BMX2 with CTS-B is time-dependent and enzyme concentration-dependent. Although CTS-B expression varied between cell lines, all showed significant uptake of BMX2 and 68Ga-BMX2. In vivo optical and PET imaging showed a high tumor uptake of BMX2 and 68Ga-BMX2 and accumulation for more than 24 h. 90Y-BMX2 could significantly inhibit HeLa tumor growth. The development of 68Ga/90Y-BMX2, a radioactive and fluorescent dual modality theranostic agent, demonstrated an effective theranostic approach for PET diagnostic imaging, fluorescence imaging, and radionuclide therapy of cancers, which may have a potential for clinical translation for cancer theranostics in the future.  \nKEYWORDS: cysteine cathepsin B, activity-based probe, multimodality imaging, cancer theranostic, positron emission tomography  \n1. INTRODUCTION  \nCancer invasion, metastasis, and drug resistance are severe challenges in clinical management and usually cause patient death. 1−3 Therefore, the assessment of tumor aggressiveness and metastases and the treatment of metastases have become important topics in oncology. Proteases have been reported that involved in many vital biological processes of cancer cells, regulating cancer invasion and metastases.4 Thus, some proteases have served as crucial diagnostics and therapeutic targets for cancer.5  \nAmong the proteases, cysteine cathepsin (CTS) is a significant family that plays critical roles in numerous physiological processes and diseases and thereby represents many theranostic targets for cancer management.6,7 There are 11 cathepsins in the human body, including CTS-B, C, F, H, K, L, O, S, V, W, and X).8 Each cathepsin has its unique role indifferent diseases. Due to the critical role of cathepsins, the development of pharmacological cathepsin inhibitors and targeting probes has been a primary research field in the world.9 Thus, noninvasive in vivo imaging of cathepsins has the  \n© 2023 The Authors. Published by American Chemical Society  \npotential to become a novel diagnostic approach, and a better understanding of the cathepsin biology of humans willempower the new generation of scientists to develop a new generation of therapeutic molecules to a broad spectrum of cancers involving cathepsin overexpression. Many selective noninvasive imaging probes have been discovered and tested for CTS screening.9 Meanwhi","cbCairawaunz2BYu","https://ap.wps.com/l/cbCairawaunz2BYu","pdf",8316851,"English","# Abstract\n# Introduction\n## Cancer invasion, metastasis, and protease targeting\n## Cathepsin family and CTS-B as a theranostic target\n## Activity-based probes and imaging rationale","[{\"question\":\"What is the main goal of developing BMX2 in this study?\",\"answer\":\"To create and evaluate a CTS-B activity-based multimodality theranostic probe for both cancer imaging and radiotherapy.\"},{\"question\":\"How were 68Ga and 90Y used in the dual-modality approach?\",\"answer\":\"BMX2 was labeled with 68Ga to enable multimodality imaging (including PET) and with 90Y to enable radiation therapy.\"},{\"question\":\"What evidence supports BMX2 specificity and activation by CTS-B?\",\"answer\":\"Fluorescent western blots using recombinant active human CTS-B and control conditions with the CTS-B inhibitor CA074 showed that BMX2 binding and activation depend on the enzyme environment and conditions, alongside imaging and uptake measurements.\"}]","Radioactive and Fluorescent Dual Modality Cysteine Cathepsin B Activity-Based Probe for Cancer Theranostics | PDF",1790251043,25]