Year-end Sale % OFF 
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.
Highlights
Prostate cancer is the most frequently diagnosed malignancy in American men
To optimize the plasma half-life of the agent for in vivo imaging applications, the substrate was further conjugated to a 40 kDa polyethylene glycol pharmacokinetic modifier (PKM) at the C-terminus at a ratio of one substrate per polymer molecule [Fig. 1(a)]
The serum prostate-specific antigen (PSA) assay was initially used to screen men with an existing diagnosis of prostate cancer,[13] and in 1994, it was approved by the FDA for prostate cancer screening
Summary
Prostate cancer is the most frequently diagnosed malignancy in American men. It is the second-leading cause of death, with one in six men having a lifetime risk of diagnosis; the therapeutic success rate for prostate cancer is significantly improved by early detection. Over the past three decades, prostate-specific antigen (PSA), a 237 amino acid, 33 kDa, extracellular serine protease, has been used extensively as a serum biomarker to screen for prostate cancer and follow therapeutic responses. In the past decade, the usefulness of PSA as a screening biomarker has
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
