Feasibility of 18F-FDG and 18F-FLT in the assessment of the early response to miR-143-mediated therapy in breast cancer xenografts

Objectives Metabolism targeting therapies have been extensively investigated as anti-cancer strategies. A number of drug candidates have been tested mostly pre-clinically with mixed success. This study was done with chemically modified miR-143 function as anti-cancer drug, to explore the potential application of miR-143-mediated inhibition of HK2 in cancer therapeutics, and we aimed to study whether 18F-FDG and 18F-FLT PET could be used for monitoring early response to treatment with miR-143 in breast cancer xenografts.

Methods Mice bearing MDA-MB-231 subcutaneous tumors were treated with chemically modified miR-143 or scrambled negative control RNA, formulated with a lipid-based delivery reagent (1.5mg/kg miR-143 agomir intravenously by tail vein injection every three days for 21 d), and tumor volumes were measured every three days. The animals were concurrently imaged on day 0, 7, 14, 21 by use of 18F-FDG, 18F-FLT, and tracer uptake was quantified with tumor to normal liver SUV ratio (TNR) on microPET/CT.

Results The administration of miR-143 agomir successfully suppressed the growth of MDA-MB-231 subcutaneous tumors, with significant change in tumor volumes being observed from day 9 after therapy on. The TNR of 18F-FDG in miR-143 treated groups showed a significant decrease compared with control groups from day 14, while 18F-FLT revealing an unstable treatment efficacy response, with great error between individuals.

Conclusions The application of miR-143 as anti-cancer drug is preliminarily feasible in breast cancer xenografts therapeutics.18F-FDG revealed more sensitivity than 18F-FLT in miR-143-mediated inhibition of HK2 in breast cancer therapeutics. This study demonstrates 18F-FDG microPET/CT could be used to evaluate the drug efficacy during anti-metabolism therapy.