Multimodality Molecular Imaging of Glioblastoma Growth Inhibition with Vasculature-Targeting Fusion Toxin VEGF121\/rGel.<\/b> <\/p>\n
J Nucl Med. 2007 Mar;48(3):445-454 <\/p>\n
Authors: Hsu AR, Cai W, Veeravagu A, Mohamedali KA, Chen K, Kim S, Vogel H, Hou LC, Tse V, Rosenblum MG, Chen X <\/p>\n
Vascular endothelial growth factor A (VEGF-A) and its receptors, Flt-1\/FLT-1 (VEGFR-1) and Flk-1\/KDR (VEGFR-2), are key regulators of tumor angiogenesis and tumor growth. The purpose of this study was to determine the antiangiogenic and antitumor efficacies of a vasculature-targeting fusion toxin (VEGF(121)\/rGel) composed of the VEGF-A isoform VEGF(121) linked with a G(4)S tether to recombinant plant toxin gelonin (rGel) in an orthotopic glioblastoma mouse model by use of noninvasive in vivo bioluminescence imaging (BLI), MRI, and PET. METHODS: Tumor-bearing mice were randomized into 2 groups and balanced according to BLI and MRI signals. PET with (64)Cu-1,4,7,10-tetraazacyclododedane-N,N’,N”,N”’-tetraacetic acid (DOTA)-VEGF(121)\/rGel was performed before VEGF(121)\/rGel treatment. (18)F-Fluorothymidine ((18)F-FLT) scans were obtained before and after treatment to evaluate VEGF(121)\/rGel therapeutic efficacy. In vivo results were confirmed with ex vivo histologic and immunohistochemical analyses. RESULTS: Logarithmic transformation of peak BLI tumor signal intensity revealed a strong correlation with MRI tumor volume (r = 0.89, n = 14). PET with (64)Cu-DOTA-VEGF(121)\/rGel before treatment revealed a tumor accumulation (mean +\/- SD) of 11.8 +\/- 2.3 percentage injected dose per gram at 18 h after injection, and the receptor specificity of the tumor accumulation was confirmed by successful blocking of the uptake in the presence of an excess amount of VEGF(121). PET with (18)F-FLT revealed significant a decrease in tumor proliferation in VEGF(121)\/rGel-treated mice compared with control mice. Histologic analysis revealed specific tumor neovasculature damage after treatment with 4 doses of VEGF(121)\/rGel; this damage was accompanied by a significant decrease in peak BLI tumor signal intensity. CONCLUSION: The results of this study suggest that future clinical multimodality imaging and therapy with VEGF(121)\/rGel may provide an effective means to prospectively identify patients who will benefit from VEGF(121)\/rGel therapy and then stratify, personalize, and monitor treatment to obtain optimal survival outcomes.<\/p>\n","protected":false},"excerpt":{"rendered":"
Multimodality Molecular Imaging of Glioblastoma Growth Inhibition with Vasculature-Targeting Fusion Toxin VEGF121\/rGel. J Nucl Med. 2007 Mar;48(3):445-454 Authors: Hsu AR, Cai W, Veeravagu A, Mohamedali KA, Chen K, Kim S, Vogel H, Hou LC, Tse V, Rosenblum MG, Chen X Vascular endothelial growth factor A (VEGF-A) and its receptors, Flt-1\/FLT-1 (VEGFR-1) and Flk-1\/KDR (VEGFR-2), are […]<\/p>\n","protected":false},"author":717,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[],"tags":[],"class_list":["post-275","post","type-post","status-publish","format-standard","hentry"],"jetpack_featured_media_url":"","_links":{"self":[{"href":"https:\/\/archive.blogs.harvard.edu\/neurovista\/wp-json\/wp\/v2\/posts\/275","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/archive.blogs.harvard.edu\/neurovista\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/archive.blogs.harvard.edu\/neurovista\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/archive.blogs.harvard.edu\/neurovista\/wp-json\/wp\/v2\/users\/717"}],"replies":[{"embeddable":true,"href":"https:\/\/archive.blogs.harvard.edu\/neurovista\/wp-json\/wp\/v2\/comments?post=275"}],"version-history":[{"count":0,"href":"https:\/\/archive.blogs.harvard.edu\/neurovista\/wp-json\/wp\/v2\/posts\/275\/revisions"}],"wp:attachment":[{"href":"https:\/\/archive.blogs.harvard.edu\/neurovista\/wp-json\/wp\/v2\/media?parent=275"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/archive.blogs.harvard.edu\/neurovista\/wp-json\/wp\/v2\/categories?post=275"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/archive.blogs.harvard.edu\/neurovista\/wp-json\/wp\/v2\/tags?post=275"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}