Positron emission tomography (PET) offers greater imaging and quantitative capabilities than conventional gamma camera imaging. Despite these advantages, the clinical use of PET for assessment of myocardial perfusion has not gained widespread acceptance, in part related to the production and imaging complexities of the currently available positron-emitting perfusion tracers. The coordination complex (62Cu)copper pyruvaldehyde thiosemicarbazone ((62Cu)Cu-PTSM) has been proposed as a potential positron-emitting flow tracer since 62Cu could be obtained at the site of a PET scanner with a 62Zn/62Cu generator which would obviate the need for an on-site cyclotron. Initial patient studies with (60Cu)Cu-PTSM and PET have demonstrated rapid uptake of the compound with excellence image quality, suggesting that Cu-PTSM has several advantages over existing PET perfusion tracers. The long-term objective of this research is to determine the utility of Cu-PTSM, labelled with 60Cu or 62Cu, with PET in the assessment of regional myocardial blood flow in patients. This proposal concerns the use of (60Cu)Cu-PTSM in patients for the relative and absolute quantification of blood flow using PET and the use of (62Cu)Cu- PTSM with PET in an experimental model of heart disease to quantify myocardial perfusion.
The specific aims of the proposal are: 1) to compare (60Cu)Cu-PTSM to (13N)-ammonia with PET in patients at rest and after pharmacologic coronary vasodilation, 2) to determine the first-pass extraction of (62Cu)cu-PTSM in an open-chest canine preparation with and without a coronary stenosis at rest and with coronary vasodilation, 3) to measure regional myocardial blood flow in dogs with and without a coronary stenosis using (62Cu)Cu-PTSM and PET data in reference to microsphere blood flow data, 4) to compare regional myocardial blood flow by counting tissue specimens for (64Cu)Cu-PTSM and (67Cu)Cu-PTSM to determine if discrepancies in quantification of blood flow by (62Cu)Cu-PTSM and PET arise from (62Cu)Cu-PTSM distribution or the tomographic technique of measuring myocardial blood flow in vivo, and 5) to apply the first-pass extraction fraction of Cu-PTSM obtained in the dog model to quantification of blood flow with (60Cu)Cu-PTSM in patients. The importance of the proposed studies is in the assessment of a new PET perfusion tracer that would improve the application of PET in the noninvasive measurement of myocardial blood flow.
