Targeted, activatable, in vivo fluorescence imaging of prostate-specific membrane antigen (PSMA)-positive tumors using the quenched humanized J591 antibody-ICG conjugate - Abstract

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.

Written by:
Nakajima T, Mitsunaga M, Bander NH, Heston WD, Choyke PL, Kobayashi H.   Are you the author?

Reference: Bioconjug Chem. 2011 Jul 10. Epub ahead of print.
doi: 10.1021/bc2002715

PubMed Abstract
PMID: 21740058

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