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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Mentored Quantitative Research Career Development Award (K25)
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Subcommittee G - Education (NCI)
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Jakowlew, Sonia B
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Johns Hopkins University
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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
Liu, Guanshu; Ray Banerjee, Sangeeta; Yang, Xing et al. (2017) A dextran-based probe for the targeted magnetic resonance imaging of tumours expressing prostate-specific membrane antigen. Nat Biomed Eng 1:977-982
Banerjee, Sangeeta R; Foss, Catherine A; Horhota, Allen et al. (2017) 111In- and IRDye800CW-Labeled PLA-PEG Nanoparticle for Imaging Prostate-Specific Membrane Antigen-Expressing Tissues. Biomacromolecules 18:201-209
Yang, Xing; Song, Xiaolei; Ray Banerjee, Sangeeta et al. (2016) Developing imidazoles as CEST MRI pH sensors. Contrast Media Mol Imaging 11:304-12
Ray Banerjee, Sangeeta; Chen, Zhengping; Pullambhatla, Mrudula et al. (2016) Preclinical Comparative Study of (68)Ga-Labeled DOTA, NOTA, and HBED-CC Chelated Radiotracers for Targeting PSMA. Bioconjug Chem 27:1447-55
Banerjee, Sangeeta Ray; Foss, Catherine A; Pullambhatla, Mrudula et al. (2015) Preclinical evaluation of 86Y-labeled inhibitors of prostate-specific membrane antigen for dosimetry estimates. J Nucl Med 56:628-34
Kiess, A P; Banerjee, S R; Mease, R C et al. (2015) Prostate-specific membrane antigen as a target for cancer imaging and therapy. Q J Nucl Med Mol Imaging 59:241-68
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
Banerjee, Sangeeta Ray; Ngen, Ethel J; Rotz, Matthew W et al. (2015) Synthesis and Evaluation of Gd(III) -Based Magnetic Resonance Contrast Agents for Molecular Imaging of Prostate-Specific Membrane Antigen. Angew Chem Int Ed Engl 54:10778-82
Behnam Azad, Babak; Banerjee, Sangeeta R; Pullambhatla, Mrudula et al. (2015) Evaluation of a PSMA-targeted BNF nanoparticle construct. Nanoscale 7:4432-42

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