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A constrained method for acetylcholinesterase density estimation with [11C]PMP and PET

¹ Radiology, Johns Hopkins University, Baltimore, Maryland; ² Radiology, University of Michigan, Ann Arbor, Michigan

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Objectives: N-[11C]methyl-piperidin-4-yl propionate ([11C]PMP), a marker for acetylcholinesterase (AChE), is kinetically distinctive and allows assuming no free ligand in tissue after 40 min or so. We propose an improvement over a published method (Nagastuka et al., 2001).

Methods: The published operational equation is: A(T) = p1xR(T) + p2xR(t)dt – p3xA(t)dt where A(T) and R(T) are time-activity curves (TACs) in regions and striatum. The method often failed to yield robust estimates of k3, an index of ACheE density because of one excessive parameter than successful reference tissue methods. A constraint was derived from the above assumption: A(T)/R(T) = p2/p3, at T>t0. Thus, the p2-p3 ratio was obtained from mean A(T)-R(T) ratio after 40 min in each region or voxel (for k3 maps) to reduce one parameter (Method B). The two methods were applied to [11C]PMP scans of subjects (n=17) for 56 cortical and subcortical regions. The subjects were normal in neurological and cognitive examination and not taking anti-cholinergic or cholinesterase inhibitor drugs.

Results: Akaike information criterion, an index of goodness of fit supported Method B over A. Regional k3 estimates of the two methods agreed (B = 0.97xA + 0.0007; R2 = 0.930). Method B had lower coefficients of variation except for fusiform and lingual gyrus. Regional k3 values given by maps agreed with those given by regional TACs for Method B (Map = 0.93xTAC + 0.002; R2=0.965) excluding the two regions.

Conclusions: We introduced a constraint for estimation of k3 for [11C]PMP. Proposed method reduced inter-subject variability without compromising fits, and made it possible to generate k3 maps for voxel-wise analysis. Thus, the method appeared to be useful in detecting changes in AChE activities in aging and neuropsychiatric conditions.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kuwabara, H. Articles by Bohnen, N. PubMed Articles by Kuwabara, H. Articles by Bohnen, N.