A targeted low molecular weight near-infrared fluorescent probe for prostate cancer

https://doi.org/10.1016/j.bmcl.2010.09.057Get rights and content

Abstract

Prostate-specific membrane antigen (PSMA) remains an active target for imaging and therapeutic applications for prostate cancer. Although radionuclide-based imaging is generally more sensitive and also has been deeply explored, near-infrared fluorescence imaging agents are simple to prepare and compatible with long-term storage conditions. In the present study, a near-infrared fluorescent imaging probe (Cy5.5-CTT-54.2) has been developed by chemical conjugation of Cy5.5N-hydroxysuccinimide ester (Cy5.5-NHS) with a potent PSMA inhibitor CTT-54.2 (IC50 = 144 nM). The probe displays a highly potency (IC50 = 0.55 nM) against PSMA and has demonstrated successful application for specifically labeling PSMA-positive prostate cancer cells in both two and three-dimensional cell culture conditions. These results suggest that the potent, near-infrared Cy5.5-PSMA inhibitor conjugate may be useful for the detection of prostate tumor cells by optical in vivo imaging.

Graphical abstract

A novel near-infrared imaging probe was synthesized, which exhibited potent PSMA inhibitory activity (IC50 = 0.55 nM) and PSMA-targeted imaging of prostate cancer cells in vitro.

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Acknowledgments

The authors extend their gratitude for technical assistance to G. Helms and W. Hiscox at the WSU Center for NMR Spectroscopy, Dr. C. Zhu at the WSU Department of Chemistry for mass spectrometry, and to both C. Davitt and V. Lynch-Holm at the WSU Franceschi Microscopy and Imaging Center. This work was supported in part by the Washington State Life Sciences Discovery Fund (LSDF 08-01 2374880) and the National Institutes of Health (1R21CA135463-01).

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