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 #
5P50CA103175-07
Application #
8555366
Study Section
Special Emphasis Panel (ZCA1-SRLB-9 (M1))
Project Start
2003-08-10
Project End
2016-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
7
Fiscal Year
2012
Total Cost
$184,483
Indirect Cost
$66,509
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Winnard Jr, Paul T; Bharti, Santosh K; Penet, Marie-France et al. (2016) Detection of Pancreatic Cancer-Induced Cachexia Using a Fluorescent Myoblast Reporter System and Analysis of Metabolite Abundance. Cancer Res 76:1441-50
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
Azad, Babak Behnam; Chatterjee, Samit; Lesniak, Wojciech G et al. (2016) A fully human CXCR4 antibody demonstrates diagnostic utility and therapeutic efficacy in solid tumor xenografts. Oncotarget 7:12344-58
Penet, Marie-France; Chen, Zhihang; Mori, Noriko et al. (2016) Magnetic Resonance Spectroscopy of siRNA-Based Cancer Therapy. Methods Mol Biol 1372:37-47
Xu, Xiang; Yadav, Nirbhay N; Zeng, Haifeng et al. (2016) Magnetization transfer contrast-suppressed imaging of amide proton transfer and relayed nuclear overhauser enhancement chemical exchange saturation transfer effects in the human brain at 7T. Magn Reson Med 75:88-96
Mascini, Nadine E; Cheng, Menglin; Jiang, Lu et al. (2016) Mass Spectrometry Imaging of the Hypoxia Marker Pimonidazole in a Breast Tumor Model. Anal Chem 88:3107-14
Chatterjee, Samit; Lesniak, Wojciech G; Gabrielson, Matthew et al. (2016) A humanized antibody for imaging immune checkpoint ligand PD-L1 expression in tumors. Oncotarget 7:10215-27
Penet, Marie-France; Kakkad, Samata; Pathak, Arvind P et al. (2016) Structure and Function of a Prostate Cancer Dissemination Permissive Extracellular Matrix. Clin Cancer Res :
Lesniak, Wojciech G; Oskolkov, Nikita; Song, Xiaolei et al. (2016) Salicylic Acid Conjugated Dendrimers Are a Tunable, High Performance CEST MRI NanoPlatform. Nano Lett 16:2248-53
Behnam Azad, Babak; Lisok, Ala; Chatterjee, Samit et al. (2016) Targeted Imaging of the Atypical Chemokine Receptor 3 (ACKR3/CXCR7) in Human Cancer Xenografts. J Nucl Med 57:981-8

Showing the most recent 10 out of 198 publications