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. ? ? In collaboration with investigators from NIMH, a fully quantitative method for determining regional rates of cerebral protein synthesis with positron emission tomography (PET) was previously developed. This method was adapted from the autoradiographic L [1-C-14]leucine method. It uses L [1-C-11]leucine as the PET radiotracer, dynamic PET scanning, and a kinetic model to measure cerebral protein synthesis rate. Studies were performed in nonhuman primates with the PET Department?s new High Resolution Research Tomograph (HRRT), which acquires brain images with ~2.5 mm resolution. These studies permitted the design of studies to be performed in normal volunteers and patients. ? ? In collaboration with investigators from NIDDK, studies were performed in nonhuman primates with the radiopharmaceutical [C-11]DTBZ. This radioligand binds to the vesicular monoamine transporter VMAT2, and was originally developed to image dopaminergic nerve terminals in brain. However, VMAT2 is also expressed in pancreatic beta cells that secrete insulin, so [C-11]DTBZ may be useful to image pancreatic beta cells and islet cell transplants in humans in vivo. Preliminary whole body PET studies performed in nonhuman primates showed uptake and retention of the radiotracer in the pancreas, and will be use to plan studies in patients with diabetes and pancreatic transplants.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL000506-03
Application #
7332508
Study Section
(PETD)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2006
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