Preclinical studies of radiopharmaceuticals for positron emission tomography (PET) are critical for their translation from the radiochemistry laboratory to their use to perform physiologic measurements in humans. Research areas include the development and validation of tracer models that describe the in vivo behavior of the compounds, and dosimetry studies to determine the radiation exposure subjects will receive. ? ? Studies were performed with [F-18]FPWAY, which binds to brain serotonin receptors. Paroxitine, which increases serotonin concentration in the synapse, was administered intravenously to see if it decreases the amount of [F-18]FPWAY binding, in order to determine if the binding level was sensitive to serotonin released by brain cells. If so, it could be used to assess serotonin levels in patients with neuropsychiatric disease. Binding in the brainstem raphe decreased, attributable due to paroxitine-induced increase in serotonin. Cerebral cortex showed increased binding (i.e., serotonin decrease), presumably due to the greater dampening effect of raphe serotonin autoreceptors causing a decrease in serotonin release in the cortex by serotonin neurons that travel from raphe to cortex. Thus, [F-18]FPWAY binding reflected transient changes in synaptic brain serotonin.? ? Imaging characteristics of a new PET scanner, the High Resolution Research Tomograph (HRRT) were studied, specifically a method for reconstructing the images (a motion-compensation OSEM list-mode algorithm for resolution recovery reconstruction). Optimal use of this algorithm requires an assessment of the resolution and noise of the images that are obtained from actual scans. PET studies were performed with several PET radiopharmaceuticals: [F 18]FCWAY, [C-11]raclopride, [C-11]DASB, and [F-18]fluorodopa. Resolution improvement and noise in the curve of tissue radioactivity versus time were measured after each iteration of the algorithm. With four successive iterations, transaxial image resolution improved by a mean of 3.0, 1.7, 1.3, and 1.2 mm respectively; noise was moderate, increasing from 5% to 9%. Therefore, with sufficient image counting statistics, improvement in image resolution can be obtained using this method with moderate increase in noise.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL000506-02
Application #
7212402
Study Section
(PETD)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2005
Total Cost
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Umhau, John C; Zhou, Weiyin; Carson, Richard E et al. (2009) Imaging incorporation of circulating docosahexaenoic acid into the human brain using positron emission tomography. J Lipid Res 50:1259-68
Smith, Carolyn B; Schmidt, Kathleen C; Bishu, Shrinivas et al. (2008) Use of acute hyperphenylalaninemia in rhesus monkeys to examine sensitivity and stability of the L-[1-11C]leucine method for measurement of regional rates of cerebral protein synthesis with PET. J Cereb Blood Flow Metab 28:1388-98
Giovacchini, Giampiero; Lang, Lixin; Ma, Ying et al. (2005) Differential effects of paroxetine on raphe and cortical 5-HT1A binding: a PET study in monkeys. Neuroimage 28:238-48
Smith, Carolyn Beebe; Schmidt, Kathleen C; Qin, Mei et al. (2005) Measurement of regional rates of cerebral protein synthesis with L-[1-11C]leucine and PET with correction for recycling of tissue amino acids: II. Validation in rhesus monkeys. J Cereb Blood Flow Metab 25:629-40
Marenco, Stefano; Carson, Richard E; Berman, Karen Faith et al. (2004) Nicotine-induced dopamine release in primates measured with [11C]raclopride PET. Neuropsychopharmacology 29:259-68
Benson, Brenda E; Carson, Richard E; Kiesewetter, Dale O et al. (2004) A potential cholinergic mechanism of procaine's limbic activation. Neuropsychopharmacology 29:1239-50
Kurdziel, Karen A; Kiesewetter, Dale O; Carson, Richard E et al. (2003) Biodistribution, radiation dose estimates, and in vivo Pgp modulation studies of 18F-paclitaxel in nonhuman primates. J Nucl Med 44:1330-9