Mutant mouse strains as models for in vivo radiotracer evaluations: [11C]methoxytetrabenazine ([11C]MTBZ) in tottering mice.
The regional brain distribution of [11C]methoxytetrabenazine ([11C]MTBZ), a high affinity radioligand for the vesicular monoamine transporter, has been examined in normal and tottering mice, which are neurological mutants. The tottering mice show significantly higher radiotracer accumulation (150-195% of controls) in all brain regions examined (striatum, cortex, hippocampus, hypothalamus, cerebellum and thalamus). The increases in [11C]MTBZ binding correlate (r = 0.91) with the reported increases in norepinephrine concentrations in these regions, and are consistent with the noradrenergic hyperinnervation characteristic of the tottering mutant mouse. These studies demonstrate that a mutant mouse model of increased innervation can be used to evaluate the sensitivity of an in vivo radiotracer measure, in this case [11C]MTBZ binding to vesicular transporters, to an increase in the numbers of binding sites in specific regions of the brain.
Kilbourn
M R
MR
Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor 48109, USA.
Sherman
P S
PS
Abbott
L C
LC
D000345:Affinity Labels; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D006023:Glycoproteins / Q000378:metabolism; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009479:Neuropeptides; D009638:Norepinephrine / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000378:metabolism; D013747:Tetrabenazine; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D000345:Affinity Labels; D002250:Carbon Radioisotopes; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D017661:Receptors, Presynaptic; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D009638:Norepinephrine; D013747:Tetrabenazine