Prostate cancer is one of the leading cancers in the U.S. population and the second leading cause of cancer death in men. Accurate prostate imaging could significantly improve accuracy of the prostate cancer diagnoses and disease progression assessments. Prostate-specific membrane antigen (PSMA) is a type II integral membrane protein that is abundantly expressed on the surface of prostate cancer cells. There are up to 1 million PSMA proteins per cell, making it an excellent target for imaging of prostate cancer. Our group has successfully developed a series of PSMA-based novel low molecular weight PET and SPECT agents for prostate cancer radionuclide imaging. Recently, we reported low molecular weight PSMA-based fluorescent imaging agents derived from conjugation of optical dyes with PSMA-binding ligand and those compounds have shown specific PSMA+ tumor uptake in mice. Optical imaging is very sensitive and can provide high contrast for tumor versus normal cells. However, it has limited penetration depth due to the scattering of the light. Photoacoustic (PA) imaging, based on the photoacoustic effect, is a noninvasive and nonionizing hybrid imaging modality that combines the high contrast of optical contrast with high spatial resolution of ultrasound imaging. It is a promising new biomedical imaging technique with great potential for clinic imaging applications. In this proposal, we are going to design, synthesize and evaluate novel PSMA-targeted low molecular weight PA imaging contrast agents for photoacoustic imaging of prostate cancer. As with our radiotracers and other optical agents, these new agents are expected to concentrate selectively within PSMA-expressing tumors, thereby enhancing the targeting specificity of the PA imaging. The ultimate goal of this project is to developing a new prostate cancer imaging method for improve the prostate cancer diagnosis and treatment monitoring.

Public Health Relevance

In this proposal, we will develop PSMA-based small molecular PA imaging agents for prostate cancer to improve the targeting specificity of this new imaging modality. The ultimate goal of this project is to developing a new prostate cancer imaging method for improve the prostate cancer diagnosis and treatment monitoring.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
3R21CA202199-02S1
Application #
9514332
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Baker, Houston
Project Start
2016-07-01
Project End
2019-06-30
Budget Start
2017-07-01
Budget End
2019-06-30
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Banerjee, Sangeeta Ray; Song, Xiaolei; Yang, Xing et al. (2018) Salicylic Acid-Based Polymeric Contrast Agents for Molecular Magnetic Resonance Imaging of Prostate Cancer. Chemistry 24:7235-7242
Zhang, Haichong K; Bell, Muyinatu A Lediju; Guo, Xiaoyu et al. (2016) Synthetic-aperture based photoacoustic re-beamforming (SPARE) approach using beamformed ultrasound data. Biomed Opt Express 7:3056-68