GRPR/PSMA Targeting Agents for Prostate Cancer Diagnosis

NIH RePORTER · VA · I01 · · view on reporter.nih.gov ↗

Abstract

According to the American Cancer Society, prostate cancer will account for an estimated 180,890 new cases and 26,120 deaths in 2016, continuing to be the most commonly diagnosed cancer and second-leading cause of cancer death in men in the United States. This research application provides rationale toward the design and development of new diagnostic agents based upon two well-validated biomarkers for early and late-stage detection of prostate cancer and is central to the research mission of the United States Department of Veterans' Affairs of seeking fundamental knowledge to enhance health, lengthen life, and reduce illness and disability of American veterans. The primary objective of this research application is to develop a metabolically stable, bivalent (dual receptor targeting), gastrin releasing peptide receptor/prostate-specific membrane antigen (GRPR/PSMA) targeting radioligand for Single Photon Emission Computed Tomography (SPECT) imaging of GRPR- and PSMA- positive prostate tumors. The GRPR and PSMA are well-validated prostate cancer biomarkers that are expressed in very high numbers on the surfaces of most prostate cancers. Because prostate cancer cells seem to differentially express specific receptors depending upon factors that may include chronicity and metastatic nature, it logically follows that a compound capable of targeting more than one biomarker would have the potential of binding to both early and chronic/metastatic stages of prostate cancer, enabling a more prompt and accurate diagnostic profile for both stages of disease. This application contains four discrete and well-delineated specific objectives: 1. Synthesis, purification, and characterization of new bivalent GRPR/PSMA-targeting radioligands. 2. To validate the cell targeting capacity of the GRPR/PSMA-targeting probes in vitro in GRPR/PSMA- expressing cells. 3. To evaluate the pharmacokinetics, pharmacology, stability, and SPECT imaging potential of the targeting probes in GRPR/PSMA-expressing prostate tumors in mice. 4. Quantitative pharmacokinetic tumor modeling and single dose acute toxicity study of the most viable molecular imaging candidate.

Key facts

NIH application ID
9932907
Project number
5I01BX003392-04
Recipient
HARRY S. TRUMAN MEMORIAL VA HOSPITAL
Principal Investigator
Charles J Smith
Activity code
I01
Funding institute
VA
Fiscal year
2020
Award amount
Award type
5
Project period
2017-04-01 → 2021-06-30