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Targeted, Activatable, In Vivo Fluorescence Imaging of Prostate-Specific Membrane Antigen (PSMA) Positive Tumors Using the Quenched Humanized J591 Antibody–Indocyanine Green (ICG) Conjugate

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† Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda Maryland 20892, United States
‡ Department of Urology, Weill Medical College of Cornell University, New York, New York 10065, United States
§ Department of Cancer Biology and Urological Institute, Cleveland Clinic, Cleveland, Ohio 44195, United States
Phone: 301-451-4220. Fax: 301-402-3191. E-mail: [email protected]
Cite this: Bioconjugate Chem. 2011, 22, 8, 1700–1705
Publication Date (Web):July 10, 2011
https://doi.org/10.1021/bc2002715
Copyright © 2011 American Chemical Society
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    Abstract

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    In patients with prostate cancer, a positive surgical margin is associated with an increased risk of cancer recurrence and poorer outcome, yet margin status cannot be determined during the surgery. An in vivo optical imaging probe that could identify the tumor margins during surgery could result in improved outcomes. The design of such a probe focuses on a highly specific targeting moiety and a near-infrared (NIR) fluorophore that is activated only when bound to the tumor. In this study, we successfully synthesized an activatable monoclonal antibody–fluorophore conjugate consisting of a humanized anti-Prostate-Specific Membrane Antigen (PSMA) antibody (J591) linked to an indocyanine green (ICG) derivative. Prior to binding to PSMA and cellular internalization, the conjugate yielded little light; however, after binding an 18-fold activation was observed permitting the specific detection of PSMA+ tumors up to 10 days after injection of a low dose (0.25 mg/kg) of the reagent. This agent demonstrates promise as a method to image the extent of prostate cancer in vivo and could assist with real-time resection of extracapsular extension of tumor and positive lymph nodes.

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