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

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Early assessment of tumor response to JAC106, an anti-tubulin agent, by 3'-deoxy-3'-[18F]fluorothymidine in preclinical tumor models
S J Lee; H Y Kang; S Y Kim; J H Chung; S J Oh; J S Ryu; S B Kim; Jong Soon Kang; S K Park; H M Kim; M H Kim; D H Moon
Bibliographic Citation
European Journal of Nuclear Medicine and Molecular Imaging, vol. 38, no. 8, pp. 1436-1448
Publication Year
Purpose: We determined whether [18F]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 [3H]colchicine binding were assessed in vitro. The effects of JAC106 on cytotoxicity, mitotic arrest, [18F]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 [18F]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 < 0.001, half maximal inhibitory concentration, IC50 = 3.15 ± 1.4) and KB-V1 (p < 0.01, IC50 = 21.84 ± 24.59) cells. Exposure to JAC106 induced mitotic arrest starting at 18 h and dose-dependently increased [18F]FLT uptake/1 × 105 cells (p < 0.05) and TK1 activity and expression in vitro. Administration of 30 mg/kg JAC106 to mice inhibited the growth of SW620 and KB-VI tumors (%T/C 3.34 and 20.6%, respectively). The baseline standardized uptake values (SUV) of SW620 and KB-V1 tumors were 0.96 ± 0.31 and 2.29 ± 0.70, respectively, with a significant difference (p < 0.01). After 3 days of treatment with 30 mg/kg JAC106, the [18F]FLT SUVs of SW620 and KB-V1 tumors, normalized to those before treatment, were 77.9 ± 22.4% (p = 0.059) and 43.2 ± 14.0% (p < 0.01), respectively. JAC106 significantly decreased the number of Ki-67-positive cells, TK1 activity, cell fraction in G0G1 phase, and tumor expression of cyclins E, A, and B1 on day 3. Conclusion: [18F]FLT PET can be used to monitor JAC106 inhibition of tumor growth, beginning 3 days after treatment. Incorporation of [18F]FLT PET may be useful in the early clinical development of JAC106
18F]FluorothymidineAnti-tubulin agentJAC106Positron emission tomography
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Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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