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 188Re-labeled recombinant human plasminogen kringle 5 (188Re‑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-[188Re(H2O)3(CO)3]+. The biodistribution study of 188Re-rhk5 showed that 188Re-rhk5 had a high initial tumor uptake and prolonged tumor retention. The highest tumor uptake of 188Re-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 188Re-rhk5-treated tumors were smaller than 188Re-, rhk5- and saline-treated controls 6 days after the treatment. In vivo 18F-FDG micro-PET imaging showed significantly reduced tumor metabolism in the 188Re-rhk5-treated mice vs. those treated with rhk5, 188Re and saline control, 1 day after treatment. Moreover, the number of microvessels was significantly reduced after 188Re-rhk5 treatment as determined by CD31 staining. Our results demonstrate that specific delivery of 188Re-rhk5 allows preferential cytotoxicity to A549 lung cancer cells and tumor vasculature. 18F-FDG micro-PET is a non-invasive imaging tool that can be utilized to assess early tumor responses to 188Re-rhk5 therapy.

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