One-step Radiosynthesis and Preclinical Evaluation of Molecular Probe [18F]FEtO-CHC Targeting Monocarboxylate Transporters for PET Imaging in Tumor-bearing Mice

Abstract

Purpose The visualization and quantitative analysis of monocarboxylate transporters (MCTs) hold significant application value in comprehending the metabolic symbiosis, acid resistance, and invasion mechanisms of tumors. Thus, we designed and synthesized a novel MCTs-targeting radiotracer [18F]FEtO-CHC and gave a comprehensive evaluation in vitro and in vivo experiments for it. Procedures The preparations for the precursor and reference of [18F]FEtO-CHC were encompassed. In vitro evaluation included compound identification, purity, stability, liposolubility, and assays in BxPC3 and 4T1 tumor cell lines. Dynamic Micro-PET imaging was performed in tumor-bearing mice to determine its in vivo characteristics. Results The synthesis of [18F]FEtO-CHC, a derivative of α-cyano-4-hydroxycinnamic acid (CHC), was achieved using a one-step method with the MCTs inhibitor (E)-ethyl 2-cyano-3-(4-hydroxyphenyl)acrylate as the lead compound. The yield obtained was 52.08 ± 6.74% (n = 7, decay corrected). The cell uptake characteristics and targeting ability towards MCTs were confirmed through cell uptake and competitive inhibition experiments conducted on BxPC3 pancreatic cancer cell line and 4T1 breast cancer cell line. The biodistribution and Micro-PET/CT imaging of tumor-bearing mice revealed the hepatic and renal metabolism-mediated excretion characteristics of [18F]FEtO-CHC, with radioactive uptake in tumors being consistent with MCTs expression levels. Conclusions Through the aforementioned studies, a one-step method was employed to successfully synthesize [18F]FEtO-CHC, which has been validated as a small molecule PET probe specifically targeting MCTs.