This project is designed to customize the educational and research activities for Dr. Sangeeta Ray to achieve two major goals. The immediate goal is for Dr. Ray to expand her current research program in the targeted imaging of prostate cancer. Specifically, she will develop a new generation of imaging agents for the prostate- specific membrane antigen (PSMA) that will employ modalities and techniques not previously described. PSMA is an attractive target for the imaging and therapy of cancer in general, as it is over-expressed not only in prostate cancer, but in most solid tumor neovasculature. The long-term goal is for Dr. Ray to acquire advanced biomedical research skills and knowledge that complement her skills as an inorganic chemist. The ultimate goal is for her to develop into an independent, interdisciplinary researcher in the area of cellular and molecular imaging of cancer. She will obtain further, formal training in cancer biology, pharmacology and ethics germane to conducting preclinical and translational research. This program will be heavily weighted toward gaining expertise regarding the biology and pharmacology of imaging - particularly using magnetic resonance (MR)-based approaches under the mentorship of two internationally recognized scientists, Drs. Martin Pomper and Zaver Bhujwalla at Johns Hopkins University. Dr. Ray will develop PSMA-targeted multimodal contrast agents (CAs) followed by evaluation of these compounds through in vitro studies and in vivo MR imaging in relevant animal models. That will allow her to evaluate the in vivo binding specificity and pharmacokinetic profile of lead compounds en route to human studies. The combination of a multimodality imaging platform with therapeutic agents will also be explored for targeted drug delivery. The ABCG2 multi- drug resistance pump has become an important target in efforts to overcome chemotherapy resistance. Target tissue selective silencing of the ABCG2 gene via RNA interference could be a new, nontoxic strategy for treating prostate and other cancers. Accordingly, Dr. Ray will focus on the following specific aims: 1) to develop multimodality low molecular weight CAs that target PSMA. 2) To develop macromolecular CAs that target PSMA. 3) To develop PSMA targeted theranostic agents for PCa. This program will provide an excellent milieu in which the applicant - under close mentorship - can become deeply involved in MR imaging for cancer. Mentorship will be geared more toward biological issues to provide a well-rounded portfolio as she progresses toward independence in biomedical imaging research.

Public Health Relevance

Prostate specific membrane antigen (PSMA) is an attractive target for the imaging and therapy of cancer in general, as it is over expressed not only in prostate cancer, but in most solid tumor neovasculature. In the research application PSMA-targeted multimodal MR contrast agents will be developed followed by evaluation of these compounds via in vitro cell imaging and in vivo MR imaging in suitable animal models. In addition, PSMA targeted compounds with therapeutic and diagnostic (theranostic) capabilities against prostate cancer will also be developed.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Mentored Quantitative Research Career Development Award (K25)
Project #
5K25CA148901-03
Application #
8490730
Study Section
Subcommittee G - Education (NCI)
Program Officer
Jakowlew, Sonia B
Project Start
2011-07-01
Project End
2016-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
3
Fiscal Year
2013
Total Cost
$116,027
Indirect Cost
$8,595
Name
Johns Hopkins University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Song, Xiaolei; Yang, Xing; Ray Banerjee, Sangeeta et al. (2015) Anthranilic acid analogs as diamagnetic CEST MRI contrast agents that feature an intramolecular-bond shifted hydrogen. Contrast Media Mol Imaging 10:74-80
Shallal, Hassan M; Minn, Il; Banerjee, Sangeeta R et al. (2014) Heterobivalent agents targeting PSMA and integrin-?v?3. Bioconjug Chem 25:393-405
Yang, Xing; Yadav, Nirbhay N; Song, Xiaolei et al. (2014) Tuning phenols with Intra-Molecular bond Shifted HYdrogens (IM-SHY) as diaCEST MRI contrast agents. Chemistry 20:15824-32
Banerjee, Sangeeta Ray; Pullambhatla, Mrudula; Foss, Catherine A et al. (2014) ??Cu-labeled inhibitors of prostate-specific membrane antigen for PET imaging of prostate cancer. J Med Chem 57:2657-69
Banerjee, Sangeeta Ray; Pomper, Martin G (2013) Clinical applications of Gallium-68. Appl Radiat Isot 76:2-13
Ray Banerjee, Sangeeta; Pullambhatla, Mrudula; Foss, Catherine A et al. (2013) Effect of chelators on the pharmacokinetics of (99m)Tc-labeled imaging agents for the prostate-specific membrane antigen (PSMA). J Med Chem 56:6108-21
Banerjee, Sangeeta Ray; Pullambhatla, Mrudula; Byun, Youngjoo et al. (2011) Sequential SPECT and optical imaging of experimental models of prostate cancer with a dual modality inhibitor of the prostate-specific membrane antigen. Angew Chem Int Ed Engl 50:9167-70