Coronary artery disease continues to be a major contributor to the cause of death in the United States. The ability to diagnosis CAD in patients at an early stage has improved over the years resulting in reducing the mortality rate. In nuclear medicine/cardiology, the SPECT and PET myocardial perfusion imaging (MPI) methods and radiopharmaceuticals used clinically over the past 10 years have offered acceptable results for accuracy and diagnosis but have now reached their limit for improvement. This research project will use an exciting new PET MPI tracer called F-18 flurpiridaz which is currently half way through phase III FDA clinical trials. This new PET tracer offers higher spatial and contrast resolution over SPECT MPI and offers higher temporal resolution and longer half life over current PET tracers making it the ideal MPI tracer for the evaluation of patients with suspected CAD. The long-term objective of this SBIR grant is to develop a quantitative method for the relative and absolute quantitation of myocardial perfusion, ventricular function, and myocardial blood flow (MBF), using the new PET MPI tracer, F-18 labeled flurpiridaz. These results will ultimately be incorporated into a commercially available diagnostic tool for clinical use. This SBIR phase I proposal will be used to demonstrate a proof-in-principle of the research and to develop a prototype of the quantitative method for analysis of flurpiridaz PET images.
The specific aims for phase I will be 1) to develop and validate a model for absolute quantitation of myocardial blood flow, 2) to develop quantitative normal databases for absolute and relative MBF, 3) to validate and optimize relative quantitation for sizing of defect and defect reversibility, and 4) to evaluate the diagnostic values of relative and absolute F-18 flurpiridaz PET quantitation for detection of CAD. The completion of phase I will produce a prototype quantitative application for the analysis of the flurpiridaz PET MPI. Following the successful completion of phase I, we will submit a phase II proposal to NIH. The research in this phase will include development of new quantitative parameters for the flurpiridaz tracer and an extensive prospective validation of the phase I projects in a much larger database obtained from the phase III FDA flurpiridaz clinical trials. The deliverable at the end of phase II will be a quantitative medical device for the comprehensive analysis of flurpiridaz PET images. The system will be commercialized using Syntermed's successful strategy through: 1) licensing to major instrumentation manufacturers, 2) direct sales to clients that use PC workstations and 3) per Web-access using the existing Syntermed Live network.

Public Health Relevance

Coronary artery disease (CAD) is the single largest cause of death in the United States. Prevention, early diagnosis, and treatment of CAD are essential to reduce the mortality. Noninvasive assessments of myocardial perfusion at rest and during stress have proved valuable for early diagnosis of CAD. The overall goal of this research project is to develop and validate methods for relative and absolute quantitation of myocardial perfusion using the new PET myocardial perfusion imaging (MPI) tracer, F-18 labeled flurpiridaz. These results will ultimately be incorporated into a commercially available diagnostic software tool for clinical use. F-18 flurpiridaz PET MPI tracer offers higher spatial and contrast resolution over SPECT thereby increasing sensitivity for detection of CAD. In addition, this new tracer has a higher myocardial extraction fraction than current PET tracers allowing more accurate quantitation of absolute myocardial blood flow and coronary flow reserve which is expected to increase sensitivity for detecting multi-vessel CAD. F-18 flurpiridaz PET MPI tracer has a longer half-life than current PET tracers (109 minutes for flurpiridaz vs1.3 minutes for Rubidium- 82) allowing production and delivery of unit doses from regional cyclotrons to PET imaging facilities. This will provide wide spread access to this PET MPI tracer without the need for an onsite cyclotron. The new flurpiridaz PET MPI tracer combined with the quantitative software tool developed in this proposal is expected to provide the most accurate and comprehensive method for quantitation of myocardial perfusion which will improve the quality and standard of care for patients suspected of CAD in the United States.

Agency
National Institute of Health (NIH)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43HL123069-01
Application #
8711570
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Danthi, Narasimhan
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Syntermed, Inc
Department
Type
DUNS #
City
Atlanta
State
GA
Country
United States
Zip Code
30342