Early assessment of tumor response to JAC106, an anti-tubulin agent, by 3′-deoxy-3′-[18F]fluorothymidine in preclinical tumor models

Purpose We determined whether [ 18 F]fluorothymidine (FLT) positron emission tomography (PET) can detect early effects on tumor proliferation of JAC106, a new anti-tubulin agent. Methods Inhibition of tubulin polymerization and [ 3 H]colchicine binding were assessed in vitro. The effects of JAC106 on cytotoxicity, mitotic arrest, [ 18 F]FLT uptake, and thymidine kinase 1 (TK1) activity were examined in SW620 and KB-V1 cells. Dose-dependent antitumor effects of JAC106 were monitored by measuring tumor growth and by dynamic [ 18 F]FLT PET imaging in mice bearing SW620 and KB-V1 tumors. The proliferation status of tumors was examined. Results JAC106 potently inhibited tubulin polymerization and decreased the viability of SW620 ( p