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
Penet, Marie-France; Shah, Tariq; Bharti, Santosh et al. (2015) Metabolic imaging of pancreatic ductal adenocarcinoma detects altered choline metabolism. Clin Cancer Res 21:386-95
Ahn, Eun Hyun; Kim, Younghoon; Kshitiz et al. (2014) Spatial control of adult stem cell fate using nanotopographic cues. Biomaterials 35:2401-10
El Khouli, Riham H; Macura, Katarzyna J; Kamel, Ihab R et al. (2014) The effects of applying breast compression in dynamic contrast material-enhanced MR imaging. Radiology 272:79-90
Nimmagadda, Sridhar; Pullambhatla, Mrudula; Lisok, Ala et al. (2014) Imaging Axl expression in pancreatic and prostate cancer xenografts. Biochem Biophys Res Commun 443:635-40
Yadav, Nirbhay N; Xu, Jiadi; Bar-Shir, Amnon et al. (2014) Natural D-glucose as a biodegradable MRI relaxation agent. Magn Reson Med 72:823-8
Gadiya, Mayur; Mori, Noriko; Cao, Maria D et al. (2014) Phospholipase D1 and choline kinase-? are interactive targets in breast cancer. Cancer Biol Ther 15:593-601
Shamir, Eliah R; Pappalardo, Elisa; Jorgens, Danielle M et al. (2014) Twist1-induced dissemination preserves epithelial identity and requires E-cadherin. J Cell Biol 204:839-56
Huang, Peng; Ou, Ai-hua; Piantadosi, Steven et al. (2014) Formulating appropriate statistical hypotheses for treatment comparison in clinical trial design and analysis. Contemp Clin Trials 39:294-302
Subhawong, Ty K; Jacobs, Michael A; Fayad, Laura M (2014) Insights into quantitative diffusion-weighted MRI for musculoskeletal tumor imaging. AJR Am J Roentgenol 203:560-72
Zhu, Wenlian; Kato, Yoshinori; Artemov, Dmitri (2014) Water exchange-minimizing DCE-MRI protocol to detect changes in tumor vascular parameters: effect of bevacizumab/paclitaxel combination therapy. MAGMA 27:161-70

Showing the most recent 10 out of 142 publications