{"id":11673,"date":"2017-08-19T16:47:27","date_gmt":"2017-08-19T21:47:27","guid":{"rendered":"https:\/\/cancer.wisc.edu\/research\/?p=11673"},"modified":"2019-07-11T16:59:52","modified_gmt":"2019-07-11T21:59:52","slug":"89zr-labeled-nivolumab-for-imaging-of-t-cell-infiltration-in-a-humanized-murine-model-of-lung-cancer","status":"publish","type":"post","link":"https:\/\/wwwtest.cancer.wisc.edu\/research\/89zr-labeled-nivolumab-for-imaging-of-t-cell-infiltration-in-a-humanized-murine-model-of-lung-cancer\/","title":{"rendered":"89Zr-labeled nivolumab for imaging of T-cell infiltration in a humanized murine model of lung cancer"},"content":{"rendered":"<div>\n<div id=\"S1\" class=\"sec sec-first\">\n<p><em>This publication used Flow Cytometry in the course of research, as well as UWCCC&#8217;s <a href=\"https:\/\/wwwtest.cancer.wisc.edu\/research\/resources\/sairf\/\">Small Animal Imaging &amp; Radiotherapy Facility<\/a>, <a href=\"https:\/\/wwwtest.cancer.wisc.edu\/research\/resources\/epl\/\">Experimental Pathology Laboratory<\/a>.<\/em><\/p>\n<h3 id=\"S1title\">Purpose<\/h3>\n<p id=\"P1\" class=\"p p-first-last\">Nivolumab is a human monoclonal antibody that is specific for programmed cell death-1 (PD-1), a negative regulator of T-cell activation and response. Acting as an immune checkpoint inhibitor, nivolumab binds to PD-1 expressed on the surface of many immune cells and prevents ligation by its natural ligands. Nivolumab is only effective in a subset of patients and there is limited data supporting its use for diagnostic, monitoring, or stratification purposes.<\/p>\n<\/div>\n<div id=\"S2\" class=\"sec\">\n<h3 id=\"S2title\">Methods<\/h3>\n<p id=\"P2\" class=\"p p-first-last\"><sup>89<\/sup>Zr-Df-nivolumab was synthesized to map the biodistribution of PD-1-expressing tumor infiltrating T-cells\u00a0<em>in vivo<\/em>\u00a0using a humanized murine model of lung cancer. The tracer was developed by radiolabeling the antibody with the positron emitter zirconium-89 (<sup>89<\/sup>Zr). Imaging studies were validated by\u00a0<em>ex vivo<\/em>biodistribution studies, and PD-1 expression was validated by immunohistochemistry studies. Data obtained from PET imaging were used to determine human dosimetry estimations.<\/p>\n<\/div>\n<div id=\"S3\" class=\"sec\">\n<h3 id=\"S3title\">Results<\/h3>\n<p id=\"P3\" class=\"p p-first-last\">The tracer showed high binding to stimulated PD-1 expressing T-cells both\u00a0<em>in vitro<\/em>\u00a0and\u00a0<em>in vivo<\/em>. PET imaging of\u00a0<sup>89<\/sup>Zr-Df-nivolumab allowed for clear delineation of subcutaneous tumors through targeting of localized activated T-cells expressing PD-1 in the tumors and salivary glands of humanized A549 tumor-bearing mice. In addition to the tumors, salivary and lacrimal gland infiltration of T-cells was noticeably visible and confirmed via histological analysis.<\/p>\n<\/div>\n<div id=\"S4\" class=\"sec sec-last\">\n<h3 id=\"S4title\">Conclusions<\/h3>\n<p id=\"P4\" class=\"p p-first-last\">These data support our claim that PD-1-targeted agents may allow for tumor imaging\u00a0<em>in vivo<\/em>, which may assist in the design and development of new immunotherapies. In the future, noninvasive imaging of immunotherapy biomarkers may assist in disease diagnostics, disease monitoring, and patient stratification.<\/p>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Nivolumab is a human monoclonal antibody that is specific for programmed cell death-1 (PD-1), a negative regulator of T-cell activation and response&#8230;<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0},"categories":[131],"tags":[],"acf":[],"_links":{"self":[{"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/posts\/11673"}],"collection":[{"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/comments?post=11673"}],"version-history":[{"count":4,"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/posts\/11673\/revisions"}],"predecessor-version":[{"id":11681,"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/posts\/11673\/revisions\/11681"}],"wp:attachment":[{"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/media?parent=11673"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/categories?post=11673"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/tags?post=11673"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}