Development of a method for the determination of dose ratio and minimum inter-injection interval for a one-day rest-stress protocol with BMS747158 PET myocardial perfusion agent

Objectives A one-day rest-stress protocol for myocardial perfusion imaging (MPI) needs minimization of wait time between injections (WT) as shorter times require greater stress/rest dosing ratios (DR) and minimum rest dose is dictated by image statistics. We developed a method for determining the dependence of DR on WT and to identify a WT for acceptable total dose.

Methods Two-day rest-stress BMS747158 PET image data of the heart (5 adenosine (AD) and 5 exercise (EX) stress) from 20 patients with known reversible defects on Tc-99m MPI were combined to create simulated stress images by adding 16%, 23%, 49% or 100% of rest image to the stress image. These were paired with rest images, and 2-day rest/stress images and read by 3 blinded readers. Results were recorded by segment as reader response (RR) (0 to 4) and as quantitative defect severity (QDS) in % decrease.

Results RR was found to be linearly related to the QDS. In general, decreases greater than 80% of maximum were read as 0, 70% to 80% as "1", 60% to 70% as “2”, 50% to 60% as “3” and below 50% as “4”. Analysis of RR indicated that greater than 1 unit change from the 2-day data were observed in reader response in general only for the 49% and 100% blended image sets. Therefore 23% was deemed the maximum tolerable rest-to-stress contamination. Using the relationship between rest-stress contamination and dosing, it was found that, for AD a minimum DR of 2.2 was required with a 0.5 hour WT, and for EX a minimum DR of 3.0 was needed with a 1-hour WT.

Conclusions It is possible to determine maximum tolerated rest-to-stress contamination levels from modeled images. The uptake properties of BMS747158 with elevated coronary flow make it possible to tolerate a relatively low DR and short WT for AD studies while a longer WT and higher DR is needed for EX studies