Biodistribution, Pharmacokinetics and Human Clinial Phase I Study for Novel VMAT2 Radiotracer---18F FP-(+)-DTBZ

Researches showed dopamine neuron depletion at early phase of Parkinson’s disease. Since, vesicular monoamine transporter-type 2 (VMAT2) and dopamine neuron declines in parallel, VMAT2 PET image may assist in differential diagnosis Parkinson’s disease (PD) from other neurodegenerative disease. Although 11C-dihydrotetrabenazine (DTBZ) has been developed for various clinical settings, the short half life of 11C precluded its utility for large scale survey. Recently, a novel radiotracer 18F-FP-(+)-DTBZ has been developed. Their relatively long half life of 18F improves the utility and availability for imaging VMAT2 in clinical settings. We will first set up the optimal scanning parameters for 18F-FP-(+)-DTBZ animal PET imaging. The degree of radioactivity decline among neuron depletion animal models will be investigated. Other animal image using specific SPECT radioligand (i.e. 99mTc-TRODAT for dopamine transporter measurement, and 123I-ADAM for serotonin transporter measurement) will be performed in parallel for comparison. All animal images results will be confirmed by histopathology and quantitative autoradiography at the end of the study. The feasibility of brain template technique in animal image will be investigated as well. The animal data will be presented and used as supplements for phase I human clinical study application. An investigator imitated phase I clinical trail is proposed to address the feasibility for further development of 18F-FP-(+)-DTBZ in this three year project. Specifically, we will conduct a preliminary evaluation of 18F-FP-(+)-DTBZ to determine the pharmacokinetics, safety, and dosimetry of 18F-FP-(+)-DTBZ in healthy volunteers and PD patients. Secondary, we will evaluate the optimal scanning time for brain image and whether uptake and distribution of 18F-FP-(+)-DTBZ in the brain differs between subjects with PD and controls. In summary, the accomplishment of the animal and human studies addressed in this project should be able to promote the application of this novel radiotracer in the medical community for VMAT2 brain image.

Project ID:PC9902-1656
External Project ID:NSC98-2314-B182-034-MY2