Molecular imaging agents targeting specific biomarkers are becoming more prevalent in an effort to enable personalized medicine. The cost to develop novel targeted imaging agents or therapeutics can be economically detrimental as many targeted agents will impact relatively small segments of the population. The Positron Emission Tomography (PET) agent 18F-fluorodeoxyglucose (18FDG) owes its success to the fact that it targets a ubiquitous mechanism, glucose uptake, required for increased cellular metabolism that has found wide clinical relevance from oncology to heart and brain function. We propose to develop a novel class of PET imaging agents, which are substrates for a molecular transporter that is ubiquitously activated as cells response to oxidative stress. In orde for this transport system to be utilized as a novel imaging biomarker, the transporter must have sufficient promiscuity to accept substrates with an appended label. Our team has already demonstrated this vital milestone of transporter promiscuity and demonstrated in vivo uptake of cystine in tumors validated for transporter activity. The goal of this proposal is to develop the best parent substrate and radiolabel combination for maximal transport efficiency and to demonstrate in vivo imaging of cellular oxidative stress. An oxidative stress PET imaging agent would have a potential broad utility for many of the indications that include cellular oxidative stress;including neurodegenerative diseases, atherosclerosis, ischemia, organ transplant rejection, autoimmune diseases, inflammatory diseases, oncology and aging.

Public Health Relevance

Molecular imaging agents targeting specific biomarkers may facilitate the emergence of personalized medicine;however most biomarkers targeted will only impact relatively small segments of the population. We propose to develop a novel class of PET imaging agents, which are substrates for a molecular transporter that is ubiquitously activated as cells response to oxidative stress. Such an imaging agent would have a potential broad utility for many of the indications that include cellular oxidative stress;including neurodegenerative diseases, atherosclerosis, ischemia, organ transplant rejection, autoimmune diseases, inflammatory diseases, oncology and aging.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
1R01EB014250-01A1
Application #
8334253
Study Section
Special Emphasis Panel (ZRG1-SBIB-W (55))
Program Officer
Sastre, Antonio
Project Start
2012-07-02
Project End
2016-04-30
Budget Start
2012-07-02
Budget End
2013-04-30
Support Year
1
Fiscal Year
2012
Total Cost
$666,140
Indirect Cost
$336,948
Name
General Electric Global Research Center
Department
Type
DUNS #
086188401
City
Niskayuna
State
NY
Country
United States
Zip Code
12309
Webster, Jack M; Morton, Christine A; Johnson, Bruce F et al. (2014) Functional imaging of oxidative stress with a novel PET imaging agent, 18F-5-fluoro-L-aminosuberic acid. J Nucl Med 55:657-64