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J Nucl Med. 2008; 49 (Supplement 1):80P
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Neurosciences: Basic Science

Monoamines - Serotonin and Dopamine

Quantification of vesicular monoamine transporters in the primate brain with [18F]9-fluoropropyl-(+)-DTBZ

Sara Plett1, David Leung1, Agata Jurewicz1, Michael Farwell1, Mark Slifstein1, Rajesh Manchanda2, Daniel Skovronsky2, Ronald Van Heertum1, Hank Kung3 and Masanori Ichise1

1 Radiology, Columbia University, New York, New York; 2 Avid Radiopharmaceuticals, Inc., Philadelphia, Pennsylvania; 3 Radiology, University of Pennsylvania, Philadelphia, Pennsylvania

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Objectives: [11C](+)-dihydrotetrabenazine (DTBZ) has been used to quantify vesicular monoamine transporter type 2 (VMAT2). [18F]9-fluoropropyl-(+)-DTBZ (FP-DTBZ), a [F18] labeled fluoroalkyl derivative (Kung, 2007), has high specific binding in monkey brain (Kilbourn, 2007). We evaluated the feasibility of VMAT2 quantification with FP-DTBZ.

Methods: Three baboons (43 ± 20 mon) had 120 min dynamic FP-DTBZ PET (bolus 74 MBq) under isoflurane anesthesia. Metabolite corrected arterial input functions were obtained. To estimate binding potentials, BPP and BPND, 1 tissue (1T) and 2T kinetic analysis (KA) and a reference tissue model (MRTM2) with cerebellum as reference tissue were used.

Results: FP-DTBZ time activity data showed excellent reversible brain uptake with highest peak uptake in the putamen (9 ± 3 SUV, 20 min) with gradual washout. Cerebellum uptake peaked earlier (6 ± 1 SUV, 3 min) with faster washout. 2TKA was superior to 1TKA. 2TKA BPP (mL/cm3) and BPND for the putamen, caudate, thalamus, brainstem, hypothalamus and cerebral cortex (34 ± 16, 32 ± 12, 7 ± 4, 6 ± 2, 16 ± 7, 0.4 ± 1 and 3.8 ± 1.9, 3.6 ± 1.6, 0.9 ± 0.5, 0.7 ± 0.3, 1.8 ± 0.6, 0.1 ± 0.1) were strongly correlated (r2 = 0.89), as were MRTM2 BPND (4.0 ± 1.7, 3.8 ± 1.1, 1.0 ± 0.3, 0.9 ± 0.2, 2.0 ± 0.6, 0.1 ± 0.1) and 2TKA BPND (r2 = 0.95). Parametric BPND images correlated well with known VMAT2 sites.

Conclusions: FP-DTBZ [18F] allows noninvasive quantification of VMAT2 binding and should be an excellent alternative to [11C] DTBZ.

Research Support: Avid Radiopharmaceuticals, Inc.





This Article
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Right arrow Articles by Plett, S.
Right arrow Articles by Ichise, M.
PubMed
Right arrow Articles by Plett, S.
Right arrow Articles by Ichise, M.