Share Email Print
cover

Journal of Biomedical Optics • Open Access

Detection and quantification of enzymatically active prostate-specific antigen in vivo
Author(s): Guojie Ho; Jeffrey L. Morin; Jeannine Delaney; Garry Cuneo; Wael Yared; Milind Rajopadhye; Jeffrey D. Peterson; Sylvie Kossodo

Paper Abstract

Assays for blood levels of prostate-specific antigen (PSA), performed in prostate cancer detection, measure mostly inactive/complexed PSA and do not provide information regarding enzymatically active PSA, which is biologically more relevant. Thus, we designed and synthesized an enzymatically cleavable peptide sequence labeled with near-infrared (NIR) fluorophores (ex/em 740/770  nm ) and coupled it to a pharmacokinetic modifier designed to improve its plasma kinetics. In its native state, the agent, PSA750 FAST™ (PSA750), is optically quenched (<95% ) and only becomes fluorescent upon cleavage by active PSA, yielding a significant increase in signal. This activation is highly selective for PSA relative to a large panel of disease-relevant enzymes. Active PSA was detected in tumor frozen sections using PSA750 and this activity was abolished in the presence of the inhibitor, alpha-1 anti-chymotrypsin. In vivo imaging of tumor-bearing mice using fluorescence molecular tomography demonstrated a significantly higher fluorescent signal in PSA + LNCaP tumors as compared to PSA − prostate cancer 3 tumors (13.0±3.7 versus 2.8±0.8  pmol , p=0.023 ). Ex vivo imaging of tumor sections confirms PSA750-derived NIR signal localization in nonvascular tissue. This is the first report that demonstrates the feasibility and effectiveness of noninvasive, real time, fluorescence molecular imaging of PSA enzymatic activity in prostate cancer.

Paper Details

Date Published: 9 August 2013
PDF: 9 pages
J. Biomed. Opt. 18(10) 101319 doi: 10.1117/1.JBO.18.10.101319
Published in: Journal of Biomedical Optics Volume 18, Issue 10
Show Author Affiliations
Guojie Ho, PerkinElmer, Inc. (United States)
Jeffrey L. Morin, PerkinElmer, Inc. (United States)
Jeannine Delaney, PerkinElmer, Inc. (United States)
Garry Cuneo, PerkinElmer, Inc. (United States)
Wael Yared, PerkinElmer, Inc. (United States)
Milind Rajopadhye, PerkinElmer, Inc. (United States)
Jeffrey D. Peterson, PerkinElmer, Inc. (United States)
Sylvie Kossodo, PerkinElmer, Inc. (United States)


© SPIE. Terms of Use
Back to Top