[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-384094-105":59,"doc-detail-384094-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","non-invasive-pd-l1-quantification-using-18-fdk222-pet-imaging-in-cancer-immunotherapy","Non-invasive PD-L1 quantification using [18 F]DK222-PET imaging in cancer immunotherapy","","Non-invasive, early pharmacodynamic biomarkers are needed to improve combination strategies for immune checkpoint inhibitor therapy. Positron emission tomography (PET) was used to monitor target dynamics, focusing on programmed death-ligand 1 (PD-L1) expression. [18F]DK222, a peptide-based PD-L1 imaging agent, was evaluated in humanized mouse models to relate PD-L1 expression with therapy-induced changes. PET quantification assessed anti–PD-1 effects in tumors with and without MSI and validated pharmacodynamics in monotherapy and combination settings using melanoma xenografts.",{"@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/non-invasive-pd-l1-quantification-using-18-fdk222-pet-imaging-in-cancer-immunotherapy/384094/",{"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/non-invasive-pd-l1-quantification-using-18-fdk222-pet-imaging-in-cancer-immunotherapy/384094.png","ImageObject",300,407,{"name":92,"@type":93},"Stanley","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","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 purpose of using [18F]DK222-PET in this study?","Question",{"text":112,"@type":113},"To non-invasively quantify PD-L1 expression dynamics and assess therapy-induced changes during cancer immunotherapy.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was PET used to evaluate PD-L1 changes after treatment?",{"text":117,"@type":113},"PET quantification measured anti–PD-1 therapy–induced changes in PD-L1 expression in tumors with and without microsatellite instability (MSI) using humanized mouse models.",{"name":119,"@type":110,"acceptedAnswer":120},"What differences were observed between combination therapy and monotherapy?",{"text":121,"@type":113},"Combination therapy produced higher [18F]DK222 uptake in A375 tumors than monotherapy, along with immune-cell changes (including a higher number of PD-L1+ cells and a higher CD8+ to CD4+ ratio) that correlated with PET measures.","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},384094,1790459293,{"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":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":145},2336477405376,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Open access Original research  \nTo cite: Mishra A, Gupta K, Kumar D, et al. Non-invasive PD-L1 quantification using [18F] DK222-PET imaging in cancer immunotherapy. Journal for ImmunoTherapy of Cancer 2023;11:e007535 . doi:10 . 1136/ jitc-2023-007535  \n► Additional supplemental material is published online only. To view, please visit the journal online ([http://dx.doi.org/10](http://dx.doi.org/10) . 1136/jitc-2023-007535) .  \nAccepted 03 September 2023  \n© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.  \nFor numbered affiliations see end of article.  \nCorrespondence to  \nDr Sridhar Nimmagadda; [snimmag1@jhmi.edu](snimmag1@jhmi.edu)  \nNon-invasive PD-L1 quantification using [18 F]DK222-PET imaging in cancer immunotherapy  \nAkhilesh Mishra  ,1,2 Kuldeep Gupta  ,1 Dhiraj Kumar,1 Gabriela Lofland,1 Ajay Kumar Sharma  ,1 Lilja B Solnes,1 Steven P Rowe,1 Patrick M Forde,3 Martin G Pomper,1,3,4 Edward W Gabrielson,3,5 Sridhar Nimmagadda  1,3,4,6  \nABSTRACT  \nBackground Combination therapies that aim to improve the clinical efficacy to immune checkpoint inhibitors have led to the need for non-invasive and early pharmacodynamic biomarkers. Positron emission tomography (PET) is a promising non-invasive approach to monitoring target dynamics, and programmed deathligand 1 (PD-L1) expression is a central component in cancer immunotherapy strategies. [18F]DK222, a peptidebased PD-L1 imaging agent, was investigated in this study using humanized mouse models to explore the relationship between PD-L1 expression and therapy-induced changes in cancer.  \nMethods Cell lines and xenografts derived from three non-small cell lung cancers (NSCLCs) and three urothelial carcinomas (UCs) were used to validate the specificity of [18F]DK222 for PD-L1 . PET was used to quantify  \nanti-programmed cell death protein-1 (PD-1) therapyinduced changes in PD-L1 expression in tumors with and without microsatellite instability (MSI) in humanized mice. Furthermore,[18F]DK222-PET was used to validate PD-L1 pharmacodynamics in the context of monotherapy and combination immunotherapy in humanized mice bearing A375 melanoma xenografts. PET measures of PD-L1 expression were used to establish a relationship between pathological and immunological changes. Lastly, spatial distribution analysis of [18F]DK222-PET was developed to assess the effects of different immunotherapy regimens on tumor heterogeneity.  \nResults [18F]DK222-PET and biodistribution studies in mice with NSCLC and UC xenografts revealed high but variable tumor uptake at 60 min that correlated with PD-L1 expression. In MSI tumors treated with antiPD-1,[18F]DK222 uptake was higher than in control tumors. Moreover, [18F]DK222 uptake was higher in A375 tumors treated with combination therapy compared with monotherapy, and negatively correlated with final tumor volumes. In addition, a higher number of PD-L1+ cells and higher CD8+-to-CD4+ cell ratio was observed with combination therapy compared with monotherapy, and positively correlated with PET. Furthermore, spatial distribution analysis showed higher [18F]DK222 uptake towards the core of the tumors in combination therapy, indicating a more robust and distinct pattern of immune cell infiltration.  \nConclusion [18F]DK222-PET has potential as a noninvasive tool for monitoring the effects of immunotherapy  \n\n| WHAT IS ALREADY KNOWN ON THIS TOPIC |\n| --- |\n| ⇒ While cancer immunotherapy with immune checkpoint inhibitors (ICI) has advanced survival rates, it remains effective for only a subset of patients. Thereis a pressing need to precisely forecast therapeutic results and overall patient survival subsequent to ICI treatments. A common occurrence post-ICI therapy is the surge in programmed death-ligand 1 (PD-L1) expression at the tumor site due to immune cell infiltration. Yet, there is a scarcity of tools designed to track these dynamic changes in PD-L1 expression, both pr","cbCaikbgsqealMGx","https://ap.wps.com/l/cbCaikbgsqealMGx","pdf",12274703,13,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusion\n# What this study adds\n# How this study might affect research, practice or policy","[{\"question\":\"What is the purpose of using [18F]DK222-PET in this study?\",\"answer\":\"To non-invasively quantify PD-L1 expression dynamics and assess therapy-induced changes during cancer immunotherapy.\"},{\"question\":\"How was PET used to evaluate PD-L1 changes after treatment?\",\"answer\":\"PET quantification measured anti–PD-1 therapy–induced changes in PD-L1 expression in tumors with and without microsatellite instability (MSI) using humanized mouse models.\"},{\"question\":\"What differences were observed between combination therapy and monotherapy?\",\"answer\":\"Combination therapy produced higher [18F]DK222 uptake in A375 tumors than monotherapy, along with immune-cell changes (including a higher number of PD-L1+ cells and a higher CD8+ to CD4+ ratio) that correlated with PET measures.\"}]","Non-invasive PD-L1 quantification using [18 F]DK222-PET imaging in cancer immunotherapy | PDF",1790261213,33]