Faculty Bibliography

We describe the tracer kinetic analysis of [C-11]-labeled alpha-methyl-tryptophan (AMT), an analogue of tryptophan, which has been developed as a tracer for serotonin synthesis using positron emission tomography (PET) in human brain. Dynamic PET data were acquired from young healthy volunteers (n = 10) as a series of 22 scans covering a total of 60 minutes and analyzed by means of a three-compartment, four-parameter model. In addition, functional images of the K-complex were created using the Patlak-plot approach. The application of a three-compartment model resulted in low identifiability of individual k-values, especially that of k3. Model identifiability analysis using a singular value decomposition of the final sensitivity matrix showed parameter identifiability to increase by 50% when the Patlak-plot approach was used. K-complex values derived by the Patlak-plot approach overestimated the compartmental values by 10 to 20%, because of the violation of the dynamic equilibrium assumption. However, this bias was fairly constant in all structures of the brain. The rank order of K-complex values from different brain regions corresponded well to the regional concentrations of serotonin in human brain (P < 0.0001). These results indicate that the Patlak-plot method can be readily applied to [C-11]AMT data in order to create functional images of the K-complex, reflecting serotonin synthesis rate, within an acceptable error margin.

Positron Emission Tomography (PET) with 2-deoxy-2 [18F]-fluoro-D-glucose provides a measure of functional brain activity, particularly in the dendritic field. In CLN3 (juvenile neuronal ceroid lipofuscinosis or juvenile Batten disease, with fingerprint inclusions) hypometabolism slowly spreads from calcarine to anterior areas, sparing subcortical structures and brainstem. In CLN2 (late infantile neuronal ceroid lipofuscinosis or Jansky-Bielschowsky disease, with curvilinear inclusions) degeneration is rapid with generalized cortical and subcortical hypometabolism. This is associated with rapidly progressive cerebral atrophy on anatomical neuroimaging. A 4-year-old child with CLN2 scanned with PET 13 months after the clinical onset showed hypometabolism, severe in the thalamus and mild in cortical areas. Three other patients with CLN2 had severe generalized hypometabolism and brain atrophy. Longitudinal PET studies in CLN may provide key insights into degenerative processes.