# Molecular Imaging Reagents for Prostate Cancer Theranostics

> **NIH NIH P41** · JOHNS HOPKINS UNIVERSITY · 2020 · $240,484

## Abstract

SUMMARY for TR&D 1
Prostate cancer (PCa) is the second leading cause of death from cancer in men in the U.S. The vast majority of
men dying of PCa continue to succumb to metastatic castration-resistant disease. There is a compelling need
to find effective treatments for metastatic PCa. Our purpose in TR&D1 of the BTRC is to successfully develop
prototype theranostic molecular imaging platforms to pursue novel avenues of (i) detecting and targeting the
focal adhesion kinase (FAK) mechanotransduction pathway that allow cells to migrate (Aims 1a and b), (ii)
detecting and eliminating activated cancer associated fibroblasts (CAFs) that play an important role in the
formation of a prometastatic extracellular matrix (ECM) in PCa (Aim 2), and (iii) developing prostate specific
antigen (PSMA)-targeted nanoparticles (NPs) to deliver siRNA to downregulate programmed death ligand 1 (PD-
L1) together with a prodrug enzyme, to exploit the activation of the immune system, together with localized cell
killing, in locally advanced and metastatic PCa (Aim 3). Optical and PET imaging reporters will be integrated
into the platforms to achieve spatial and temporal visualization of the NPs in vivo for precision medicine. PSMA,
a type II integral membrane protein that is abundantly expressed on the surface of PCa in castration-resistant,
advanced and metastatic disease, provides a unique advantage to deliver PSMA-specific NPs for effective
control and treatment of locally advanced or metastatic PCa. These studies will result in the accelerated
development of FAK PET imaging probes with near term clinical translation that will have a direct impact on the
selection of patients for ongoing FAK inhibitor treatment trials. Mechanical movement of cancer cells is a
prerequisite for invasion and metastasis. NPs that achieve PCa-specific downregulation of FAK using PSMA-
specific delivery will provide cancer-specific downregulation of cell migration, a key step in the metastatic
cascade. Similarly, detection of CAFs in tumors with imaging will provide a distinct advantage over biopsy
specimens in evaluating CAF numbers as a marker of aggressiveness. CAF elimination with phototherapy may
provide a strategy to reduce or eliminate PCa metastasis. The development of NPs to improve immunotherapy
in PCa through theranostics and their translation will represent a significant advance in this field since PCa has
traditionally not responded well to immunotherapy. TR&D1 will also serve as the Pre-Clinical Validation Core
that will, through close interactions with the CPs and other TR&Ds, develop and disseminate novel molecular
imaging theranostic agents that will advance precision medicine of cancer worldwide.

## Key facts

- **NIH application ID:** 9984355
- **Project number:** 5P41EB024495-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Zaver M. Bhujwalla
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $240,484
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984355

## Citation

> US National Institutes of Health, RePORTER application 9984355, Molecular Imaging Reagents for Prostate Cancer Theranostics (5P41EB024495-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9984355. Licensed CC0.

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