title: Evaluation of biodistribution and antitumor effects of (188)Re-rhk5 in a mouse model of lung cancer.
abstract: Targeting drugs to receptors involved in tumor angiogenesis is considered to be a novel and promising approach to improve cancer treatment. This study aimed to evaluate the anti-tumor efficacy of (188)Re-labeled recombinant human plasminogen kringle 5 ((188)Re‑rhk5) through [18F]-fluorodeoxyglucose (FDG) micro-positron emission tomography (PET). Radiolabeled rhk5 was obtained by conjugating the hystidine (6 x His) group at the carbon end of rhk5 with fac-[(188)Re(H(2)O)(3)(CO)(3)](+). The biodistribution study of (188)Re-rhk5 showed that (188)Re-rhk5 had a high initial tumor uptake and prolonged tumor retention. The highest tumor uptake of (188)Re-rhk5 (3.65±0.82% ID/g) was found 2 h after injection which decreased to 0.81±0.14% ID/g 12 h after injection. Following therapy, tumor size measurement indicated that (188)Re-rhk5-treated tumors were smaller than (188)Re-, rhk5- and saline-treated controls 6 days after the treatment. In vivo 18F-FDG micro-PET imaging showed significantly reduced tumor metabolism in the (188)Re-rhk5-treated mice vs. those treated with rhk5, (188)Re and saline control, 1 day after treatment. Moreover, the number of microvessels was significantly reduced after (188)Re-rhk5 treatment as determined by CD31 staining. Our results demonstrate that specific delivery of (188)Re-rhk5 allows preferential cytotoxicity to A549 lung cancer cells and tumor vasculature. (18)F-FDG micro-PET is a non-invasive imaging tool that can be utilized to assess early tumor responses to (188)Re-rhk5 therapy.
authors.affiliation: Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.forename: Sheng
authors.initials: S
authors.lastname: Liang
authors.forename: Yufei
authors.initials: Y
authors.lastname: Ma
authors.forename: Hua
authors.initials: H
authors.lastname: Shen
authors.forename: Haoping
authors.initials: H
authors.lastname: Xu
authors.forename: Biao
authors.initials: B
authors.lastname: Li