Metastasis is the leading cause of death from prostate cancer (PCa) and there is a compelling need to find effective treatments for metastatic disease. Theranostic imaging, where diagnosis is combined with therapy, is particularly suitable for a disease that is as complex as cancer, especially now that genomic and proteomic profiling can provide an extensive ?fingerprint'of each tumor. The two aims in this research component converge towards developing theranostic nanoplex platforms for treatment of metastatic PCa.
In Aim 1 ?First-in-man'clinical studies will evaluate prostate-specific membrane antigen (PSMA) based detection of metastatic PCa using positron emission tomography (PET). These clinical studies are the successful culmination of research initiated through an ICMIC pilot project awarded to Dr. Pomper in 2003.
In Aim 1 we will perform a first-in-man study of [18F]DCFBC in metastatic PCa as well as a preliminary comparison of its ability to detect metastatic disease with that of [11C]choline. Proof-of-principle preclinical studies will be performed in parallel in Aim 2, to develop and optimize a theranostic PSMA-targeted prototype nanoplex carrying multimodality imaging reporters together with small interfering RNA (siRNA) and a prodrug enzyme. Each component of the nanoplex is carefully selected to allow us to evaluate each of its aspects i.e., image-guided delivery of nanoplex, siRNA-mediated downregulation, and conversion of prodrug to cytotoxic drug by the prodrug enzyme, with noninvasive imaging. These clinical and preclinical studies will identify new effective image-guided strategies to achieve cancer cell-specific treatment for metastatic PCa. In this era of personalized molecular medicine, the effective implementation of theranostic agents may achieve successful treatment for metastatic PCa, a goal that remains elusive despite the technological advances of the 21st century.

Public Health Relevance

This research component will have a 'first-in-man'clinical component to develop PSMA-based detection of metastatic prostate cancer using PET imaging. In preclinical studies, advances in image-guided prodrug therapy together with downregulation of choline metabolism using small interfering RNA (siRNA) will be exploited to target metastatic prostate cancer cells selectively, while sparing normal tissue.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA103175-09
Application #
8728582
Study Section
Special Emphasis Panel (ZCA1-SRLB-9)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
9
Fiscal Year
2014
Total Cost
$186,681
Indirect Cost
$67,199
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
van Zijl, Peter C M; Lam, Wilfred W; Xu, Jiadi et al. (2017) Magnetization Transfer Contrast and Chemical Exchange Saturation Transfer MRI. Features and analysis of the field-dependent saturation spectrum. Neuroimage :
Penet, Marie-France; Kakkad, Samata; Pathak, Arvind P et al. (2017) Structure and Function of a Prostate Cancer Dissemination-Permissive Extracellular Matrix. Clin Cancer Res 23:2245-2254
Malek, Reem; Gajula, Rajendra P; Williams, Russell D et al. (2017) TWIST1-WDR5-Hottip Regulates Hoxa9 Chromatin to Facilitate Prostate Cancer Metastasis. Cancer Res 77:3181-3193
Krishnamachary, Balaji; Stasinopoulos, Ioannis; Kakkad, Samata et al. (2017) Breast cancer cell cyclooxygenase-2 expression alters extracellular matrix structure and function and numbers of cancer associated fibroblasts. Oncotarget 8:17981-17994
Xu, Jiadi; Chan, Kannie W Y; Xu, Xiang et al. (2017) On-resonance variable delay multipulse scheme for imaging of fast-exchanging protons and semisolid macromolecules. Magn Reson Med 77:730-739
Chatterjee, Samit; Lesniak, Wojciech G; Miller, Michelle S et al. (2017) Rapid PD-L1 detection in tumors with PET using a highly specific peptide. Biochem Biophys Res Commun 483:258-263
Miller, Michelle S; Maheshwari, Sweta; McRobb, Fiona M et al. (2017) Identification of allosteric binding sites for PI3K? oncogenic mutant specific inhibitor design. Bioorg Med Chem 25:1481-1486
Chen, Ying; Chatterjee, Samit; Lisok, Ala et al. (2017) A PSMA-targeted theranostic agent for photodynamic therapy. J Photochem Photobiol B 167:111-116
Jin, Jiefu; Krishnamachary, Balaji; Mironchik, Yelena et al. (2016) Phototheranostics of CD44-positive cell populations in triple negative breast cancer. Sci Rep 6:27871
Chan, Kannie W Y; Jiang, Lu; Cheng, Menglin et al. (2016) CEST-MRI detects metabolite levels altered by breast cancer cell aggressiveness and chemotherapy response. NMR Biomed 29:806-16

Showing the most recent 10 out of 210 publications