Shape analysis method can be used for limited non-invasive estimation of striatal and cerebellar [11C]-PMP k3 hydrolysis rates

Objectives [11C]N-methylpiperidinyl propionate ([11C]-PMP) is an irreversible radiotracer used to estimate acetylcholinesterase hydrolysis rate in the brain. Two non-invasive kinetic analysis models have been described to calculate [11C]-PMP k3 hydrolysis rate, i.e. the Nagatsuka analysis (Nagatsuka, 2001) and the shape analysis method (Koeppe, 1999). The Nagatsuka method cannot be used to estimate [11C]-PMP k3 hydrolysis rate in the putamen and caudate nucleus and theoretically may give negative values for the cerebellum if enzymatic activity is higher in the cerebellum than the striatum. The objective was to determine the appropriateness of the shape analysis method for determining striatal and cerebellar [11C]-PMP k3 hydrolysis rate. The arterial blood plasma input function was used as the reference standard.

Methods 81 (39/42 M/F, 61.2 ± 10.7 years) healthy participants (N=22) and patients (N=59) with variable neurodegenerative pathology underwent [11C]-PMP PET imaging with an arterial line placed for blood plasma sampling. The shape analysis method was analyzed as described before (Koeppe, 1999). PET-based volumes of interest were defined for the putamen, caudate nucleus, and cerebellum. Correlation analysis was performed to determine the degree of agreement of k3 hydrolysis rate between arterial line input function and shape analysis method.

Results The shape analysis method correlated significantly with arterial input based [11C]-PMP k3 hydrolysis rate of the putamen (r=0.401, p<0.0001), caudate nucleus (r=0.368, p=0.001), and cerebellum (r=0.392, p=0.001).

Conclusions Results showed that striatal and cerebellar [11C]-PMP k3 hydrolysis rate can be estimated by the shape analysis method, although with a compressed dynamic range.

Research Support NIH P01 NS015655 & R01 NS07085