Imaging Prostate Cancer (PCa) Phenotype and Evolution
Abstract
The goal of the project is to investigate the potential of inhibiting iron metabolism to inhibit prostate cancer growth. Specifically, we will study Deferiprone, an iron chelator, and focus on its effect on aconitase in prostate tumors. It has been shown that changes in citrate metabolism at the level of mitochondrial aconitase, is an early change in carcinogenesis in the prostate. This change in metabolism is detectable by magnetic resonance. The project includes both in vitro and in vivo studies to determine its potential utility for clinical translation. Our findings to date include that deferiprone in 4 cell lines has an IC50 (inhibitory concentration for 50% of cells) of about 50uM (typical serum levels after standard dose = 100uM), inhibits tumor growth in vivo in 2 transgenic tumor models, and results in decreased tumor iron concentration as measured by MRI. We have had difficulty with monitoring in vivo glucose metabolism and thus switched to using iron imaging as a non-invasive surrogate for monitoring DFP activity. In year 3 we will finish developing and evaluating aconitase knockdown cell lines to test the hypothesis that DFP's iron chelating activity decreases activity and expression of aconitase.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2015
- Accession Number
- ADA626592
Entities
People
- Jason A Koutcher
Organizations
- Memorial Sloan Kettering Cancer Center