Search

Author(s): M. F. DeCamp (corresponding author) [1]; D. A. Reis [1]; P. H. Bucksbaum [1]; B. Adams [2]; J. M. Caraher [1]; R. Clarke [1]; C. W. S. Conover [3]; [...]

The in vivo behavior of (-)-[11C]phenylephrine (PHEN) is compared with the structurally similar but monoamine oxidase (MAO)-resistant analog (-)-[11C]-m-hydroxyephedrine (HED), which is an established heart neuronal marker. The chiral synthesis of PHEN has been achieved by direct methylation of (-)-m-octopamine with either 11CH3I or CF3SO311CH3. These synthetic methods produced PHEN with a specific activity ranging from 500-1000 Ci/mmol, in a radiochemical yield of > 50% (EOS) and with an enantiomeric purity of 94-96%. Biodistribution studies indicate the initial uptake of PHEN in rat heart is approximately half that of HED. Following PHEN injection, radioactivity egresses from the rat heart rapidly, with 50% washout occurring from 5 to 60 min. HED washout over this interval was less than 20%. The heart neuronal selectivity determined by desipramine blockade of the amine neuronal transporter was 75-77% compared to 92-95% for HED. Ring-labeled (-)-[3H]phenylephrine gave tissue-to-blood concentration ratios and heart clearance times very similar to PHEN. Rats pretreated with the MAO A inhibitor clorgyline showed higher levels of activity in the heart at 15 and 60 min. Tandem PET studies with PHEN and HED in the closed-chest dog provided excellent heart images with both tracers.

The utilization of image-derived input functions is becoming common in quantitative PET studies of the heart. Consequently, imaging protocols must be designed to sample both blood and tissue concentrations adequately. Most clinical imaging protocols consist of a series of short initial scans to measure the rapid change in blood and tissue tracer concentration levels, followed by scans of gradually increasing length. The number of initial short scans must be matched to the shape of the input function. In this paper, noise-free simulation studies were performed to evaluate the effect of temporal sampling on estimates of the parameters of a two-compartment kinetic model. In addition, the consequences of varying tracer infusion length and timing were studied. The kinetic model parameters' bias decreased when infusion times were lengthened or sampling rates increased. Our results indicated that tracer infusions of 30 sec were best suited for these studies. Two currently employed clinical imaging protocols were then optimized for use with this infusion scheme. Ten initial scans with durations of 10 sec, or twenty of 5 sec length produced unbiased estimates of kinetic model parameters that describe myocardial physiology. Noisy simulations with the equivalent of one million events confirmed these results.

The distortions inherent in PET images of the human heart due to finite image resolution and cardiac motion limit the capability to evaluate physiology quantitatively. A method based on a simple geometrical model of region of interest representations in physical space has been developed to minimize these distortions. In this paper, simulation studies have been performed to evaluate the noise characteristics of the method. This study demonstrates that unbiased estimates of kinetic model parameters which describe myocardial physiology can be measured with an accuracy of 7%-15% for scale-related parameters and 4%-16% for shape-related parameters of kinetic models in studies with the equivalent of 1 million events. Application of the techniques developed in this paper for the measurement of myocardial blood flow in eight dogs (14 independent flow states) shows a strong correlation with microsphere determined blood flow in the same animals (slope = 1.022, intercept = -0.18, r = 0.96).