{"id":11677,"date":"2017-08-18T16:54:04","date_gmt":"2017-08-18T21:54:04","guid":{"rendered":"https:\/\/cancer.wisc.edu\/research\/?p=11677"},"modified":"2019-07-11T16:59:33","modified_gmt":"2019-07-11T21:59:33","slug":"targeting-angiogenesis-for-radioimmunotherapy-with-a-177lu-labeled-antibody","status":"publish","type":"post","link":"https:\/\/wwwtest.cancer.wisc.edu\/research\/targeting-angiogenesis-for-radioimmunotherapy-with-a-177lu-labeled-antibody\/","title":{"rendered":"Targeting angiogenesis for radioimmunotherapy with a 177Lu-labeled antibody"},"content":{"rendered":"<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>\u00a0(SAIRF), and <a href=\"https:\/\/wwwtest.cancer.wisc.edu\/research\/resources\/epl\/\">Experimental Pathology Laboratory<\/a>\u00a0(EPL).<\/em><\/p>\n<div id=\"S1\" class=\"sec sec-first\">\n<h3 id=\"S1title\">Purpose<\/h3>\n<p id=\"P1\" class=\"p p-first-last\">Increased angiogenesis is a marker of aggressiveness in many cancers. Targeted radionuclide therapy of these cancers with angiogenesis-targeting agents may curtail this increased blood vessel formation and slow the growth of tumors, both primary and metastatic. CD105, or endoglin, has a primary role in angiogenesis in a number of cancers, making this a widely-applicable target for targeted radioimmunotherapy.<\/p>\n<\/div>\n<div id=\"S2\" class=\"sec\">\n<h3 id=\"S2title\">Methods<\/h3>\n<p id=\"P2\" class=\"p p-first-last\">The anti-CD105 antibody, TRC105 (TRACON Pharmaceuticals), was conjugated with diethylenetriaminepentaacetic acid (DTPA) for radiolabeling with\u00a0<sup>177<\/sup>Lu (t<sub>1\/2<\/sub>: 6.65 days). Balb\/c mice were implanted with 4T1 mammary carcinoma cells, and five study groups were employed:\u00a0<sup>177<\/sup>Lu-only, TRC105 only,\u00a0<sup>177<\/sup>Lu-DTPA-IgG (a nonspecific antibody),\u00a0<sup>177<\/sup>Lu-DTPA-TRC105 low dose, and\u00a0<sup>177<\/sup>Lu-DTPA-TRC105 high dose. Toxicity of the agent was monitored through body weight measurements and analysis of blood markers. Biodistribution studies of\u00a0<sup>177<\/sup>Lu-DTPA-TRC105 were also performed at 1 and 7 days post-injection.\u00a0<em>Ex vivo<\/em>\u00a0histology studies of various tissues were conducted at 1, 7, and 30 days post-injection of high dose\u00a0<sup>177<\/sup>Lu-DTPA-TRC105.<\/p>\n<\/div>\n<div id=\"S3\" class=\"sec\">\n<h3 id=\"S3title\">Results<\/h3>\n<p id=\"P3\" class=\"p p-first-last\">Biodistribution studies indicated steady uptake of\u00a0<sup>177<\/sup>Lu-DTPA-TRC105 in 4T1 tumors between 1 and 7 days post-injection (14.3 \u00b1 2.3 %ID\/g and 11.6 \u00b1 6.1 %ID\/g, respectively; n = 3) and gradual clearance from other organs. Significant inhibition of tumor growth was observed in the high dose group, with a corresponding significant increase in survival (p&lt;0.001, all groups). In most study groups (all except the nonspecific IgG), mouse body weight did not decrease by more than 10%, indicating the safety of the injected agents. Serum ALT quantification indicated steady levels and no damage to the liver (a primary clearance organ of the agent), confirmed with\u00a0<em>ex vivo<\/em>\u00a0histological analyses.<\/p>\n<\/div>\n<div id=\"S4\" class=\"sec sec-last\">\n<h3 id=\"S4title\">Conclusion<\/h3>\n<p id=\"P4\" class=\"p p-first-last\"><sup>177<\/sup>Lu-DTPA-TRC105, when administered at a sufficient dose, is able to curtail tumor growth and provide a significant survival benefit without off-target toxicity. Thus, this targeted agent holds promise to be combined with other treatment options in order to slow tumor growth and allow for greater therapeutic indices.<\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Increased angiogenesis is a marker of aggressiveness in many cancers. Targeted radionuclide therapy of these cancers with angiogenesis-targeting agents may curtail this increased blood vessel formation and slow the growth of tumors, both primary and metastatic&#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\/11677"}],"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=11677"}],"version-history":[{"count":3,"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/posts\/11677\/revisions"}],"predecessor-version":[{"id":11680,"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/posts\/11677\/revisions\/11680"}],"wp:attachment":[{"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/media?parent=11677"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/categories?post=11677"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/tags?post=11677"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}