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.
