Nearinfrared fluorescence imaging of prostate cancer using heptamethine carbocyanine dyes

Abstract

Nearinfrared fluorescence (NIRF) imaging is an attractive novel modality for the detection of cancer. A previous study defined two organic polymethine cyanine dyes as ideal NIRF probes, IR783 and its derivative MHI148, which have excellent optical characteristics, superior biocompatibility and cancer targeting abilities. To investigate the feasibility of NIRF dyemediated prostate cancer imaging, dye uptake and subcellular colocalization were investigated in PC3, DU145 and LNCaP human prostate cancer cells and RWPE1 normal prostate epithelial cells. Different organic anion transporting peptide (OATP) inhibitors were utilized to explore the potential role of the OATP subtype, including the nonspecific OATP inhibitor bromosulfophthalein, the OATP1 inhibitor 17βestradiol, the selective OATP1B1 inhibitor rifampicin and the selective OATP1B3 inhibitor cholecystokinin octapeptide. NIRF dyes were also used for the simulated detection of circulating tumor cells and the rapid detection of prostate cancer in human prostate cancer tissues and prostate cancer xenografts in mouse models. The results revealed that the cancerspecific uptake of these organic dyes in prostate cancer cells occurred primarily via OATP1B3. A strong NIRF signal was detected in prostate cancer tissues, but not in normal tissues that were stained with IR783. Prostate cancer cells were recognized with particular NIR fluorescence in isolated mononuclear cell mixtures. The results of the present study demonstrated that NIRF dyemediated imaging is a feasible and practicable method for prostate cancer detection, although further investigative studies are required before clinical translation.