Synthesis of IR-780 dye-conjugated abiraterone for prostate cancer imaging and therapy

Abstract

Near-infrared fluorescence (NIRF) imaging is a novel imaging modality that allows for detection and real‑time monitoring of various pathophysiological states. IR-780 iodide has been used as an ideal platform to construct theranostic agents for cancer imaging and therapy. Abiraterone is a 17α‑hydroxylase/C17, 20‑lyase (CYP17) inhibitor that has been approved for use in patients with prostate cancer after androgen deprivation therapy. We report the synthesis and characterization of IR-780 conjugated abiraterone for the dual purpose of prostate cancer imaging and therapy. The new compound Abi-780 retained the excellent photophysical characteristics and NIRF imaging property of IR-780 dye. Abi-780 preferentially accumulated in plasmonic organelles of prostate cancer cells but not in normal prostate epithelial cells. Dose-dependent inhibition of cultured prostate cancer cells by Abi-780 was found. Abi-780 at 20 µM significantly reduced the capabilities of colony formation and migration/invasion potential as well as increasing the apoptosis rate of prostate cancer cells. NIRF imaging using Abi-780 selectively identified the tumors in mice bearing prostate cancer xenografts. Moreover, Abi-780 treatment significantly retarded the tumor growth. No severe systemic toxicity was observed in mice with daily injection of high-dose Abi-780 for one month. In conclusion, biocompatible Abi-780 is highly effective both in prostate cancer imaging and therapy. Constructing theranostic agents using the NIRF dye platform holds great promise in accurate diagnosis and targeted treatment of cancer.