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Clinical Investigations |
1 Chemistry Department, Brookhaven National Laboratory, Upton, New York
2 Medical Department, Brookhaven National Laboratory, Upton, New York
3 Department of Applied Mathematics and Statistics, State University of New York Stony Brook, Stony Brook, New York
Monoamine oxidase (MAO) regulates neurotransmitter concentration in the brain and is also an important detoxifying enzyme in peripheral organs. It occurs in 2 subtypes, MAO A and MAO B. Their relative ratios in different organs are variable, depending on the particular organ and species, making it difficult to extrapolate measures from animals to humans. The purpose of this study was to investigate the feasibility of imaging MAO B in peripheral organs in humans with PET. Methods: Nine healthy subjects (7 males, 2 females; mean age ± SD, 37 ± 7 y) received 2 dynamic PET studies of the torso area 2 h apart with 11C-L-deprenyl and deuterium-substituted 11C-L-deprenyl (11C-L-deprenyl-D2). Time-activity curves for heart, lungs, liver, kidneys, and spleen and arterial plasma input were measured for each study. The uptake at plateau and the incorporation quotient (IQ = uptake/plasma input) as well as model terms K1 (which is a function of blood flow) and k3 and 
k3 (which are kinetic terms proportional to MAO B) were compared to identify organs that showed reduced values with deuterium substitution (deuterium isotope effect) characteristic of MAO B. In addition, a sensitivity analysis compared the 2 tracers with respect to their ability to quantify MAO B. Results: Heart, lungs, kidneys, and spleen showed a robust deuterium isotope effect on uptake, IQ, k3, and k3. The arterial plasma input function was significantly larger for 11C-L-deprenyl-D2 than for 11C-L-deprenyl. Liver time-activity curves were not affected by deuterium substitution and model terms could not be estimated. In organs showing an isotope effect, k3 showed the rank order: kidneys 
heart > lungs = spleen. A sensitivity analysis showed that 11C-L-deprenyl-D2 is a better index of MAO activity than 11C-L-deprenyl. Conclusion: This study demonstrates that (a) the deuterium isotope effect is useful in assessing the binding specificity of labeled deprenyl to peripheral MAO B; (b) MAO B can be visualized and quantified in the heart, lungs, kidneys, and spleen but not in the liver; (c) with the exception of the liver, which cannot be measured, MAO B activity is highest in the kidneys and heart; and (d) quantitation in organs having high levels of MAO B is improved by the use of 11C-L-deprenyl-D2, similar to prior studies on the brain. This study indicates that 11C-L-deprenyl-D2 will be useful for measuring the effects of different variables, including tobacco smoke exposure on MAO B activity in peripheral organs in humans.
Key Words: PET • monoamine oxidase B • peripheral organs
This article has been cited by other articles:
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  R. M. Baldwin Imaging MAO-A Levels by PET Using the Deuterium Isotope Effect J. Nucl. Med., September 1, 2005; 46(9): 1411 - 1413. [Full Text] [PDF]
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J. S. Fowler, J. Logan, G.-J. Wang, N. D. Volkow, F. Telang, W. Zhu, D. Franceschi, C. Shea, V. Garza, Y. Xu, et al. Comparison of Monoamine Oxidase A in Peripheral Organs in Nonsmokers and Smokers J. Nucl. Med., September 1, 2005; 46(9): 1414 - 1420. [Abstract] [Full Text] [PDF]
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 J. S. Fowler, J. Logan, G.-J. Wang, N. D. Volkow, F. Telang, W. Zhu, D. Franceschi, N. Pappas, R. Ferrieri, C. Shea, et al. Inaugural Article: Low monoamine oxidase B in peripheral organs in smokers PNAS, September 30, 2003; 100(20): 11600 - 11605. [Abstract] [Full Text] [PDF]
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