Small Animal Imaging with F-18-Av-133 Targeting Vesicular Monoamine Transporter II in Cns

The vesicular monoamine transporter type II (VMAT2) is an integral part of the mechanism for vesicular packaging and storage of monoamine neurotransmitters in the synapses of the brain. VMAT2 is responsible for the movement of all three of the monoamines from the cytosol into the vesicular lumen, therefore, imaging VMAT2 in the brain can provide a measurement of the integrity of all three types of monoaminergic neurons. PET imaging with [11C](+)DTBZ has been suggested as a method for measuring selective degeneration of projection neurons in the striatum. While the clinical value of VMAT2 imaging with [11C](+)DTBZ becomes significant, the short physical half life of 11C (20 min) limits its availability and can only be used in a cyclotron installed hospital. To meet a goal with a wider application, an 18F-labeled analog of DTBZ ([18F](+)FP-DTBZ; [18F]AV-133) with a longer physical half-life (110 min) has been recently developed. In light of an increasing number of animal models related to neurodegenerative mechanism, there is an increasing interest in using dedicated small animal PET imaging to assess the characteristics of VMAT2 and their relation to human disease. In this 3-year project, the simplified reference tissue method for quantification of [18F]AV-133 imaging data in piglets will be validated, and will be applied to evaluate VMAT2 change with [18F]AV-133 imaging in neurotoxin-induced Parkinson’s disease (PD) rodents, dopamine transporter knockout (DAT KO) mice and dopamine D3 receptor knockout mice.

Project ID:PC10001-1132
External Project ID:NSC99-2314-B182-036-MY3