1. Division of Nuclear Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, U.S.A.
2. ^*Department of Neurology, University of Michigan, Ann Arbor, Michigan, U.S.A.
3. ^†Geriatrics Research, Education, and Clinical Center, Ann Arbor Veterans Administration Medical Center, Ann Arbor, Michigan, U.S.A.

Correspondence: Robert A Koeppe, Division of Nuclear Medicine, University of Michigan Medical School, 3480 Kresge III Box 0552, Ann Arbor, MI 48109, U.S.A.

Received 26 November 1996; Revised 8 April 1997; Accepted 9 April 1997.

Abstract

This work compares equilibrium to kinetic analysis of positron emission tomography data for the assessment of vesicular monoamine transporter (VMAT2) binding density using (+)--[¹¹C]dihydrotetrabenazine ((+)--[¹¹C]DTBZ). Studies were performed for 80 minutes after intravenous administration of 18 1 mCi (+)--[¹¹C]DTBZ on 9 young control subjects, 20 to 45 years of age. A 9-mCi bolus was injected over the first minute of the study, whereas the remaining 9 mCi were infused at a constant rate over the following 79 minutes. Steady-state was reached in both blood and brain by approximately 30 minutes after initiation of the study. Nonlinear least-squares analysis using two- and three-compartment models, weighted integral analysis using a two-compartment configuration, and Logan plot analysis all yielded kinetic estimates of the total tissue distribution volume, DV_tot(kin). These results were compared with equilibrium distribution volume estimates, DV_tot(eq), calculated from the tissue to metabolite corrected arterial plasma concentration ratio after 30 minutes. Kinetic modeling results from this study were in close agreement with prior bolus-injection (+)--[¹¹C]DTBZ studies. In the current study, coefficients of variation in DV_tot(kin) (19% to 23% across regions) and DV_tot(eq) (18% to 22%) were nearly identical. Equilibrium estimates of DV_tot were slightly lower than kinetic estimates, averaging 5% 9% lower (P = 0.04, paired t test) in regions of high binding density (caudate and putamen), but only 2% 6% (P = 0.09) in lower binding density regions (cortex, thalamus, cerebellum). DV_tot(eq) estimates, however, still correlated highly with DV_tot(kin) estimates (r = 0.977–0.989). Steady-state conditions can be achieved in both tissue and blood by 30 minutes, and the tissue-to-blood ratios of (+)--[¹¹C]DTBZ at equilibrium yield DV_tot(eq) measures that are in close agreement with DV_tot(kin) estimates. Thus, a simple, easily tolerated protocol using a loading bolus followed by continuous infusion can provide excellent measures of VMAT2 binding.