The in vivo dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) labelled with 11C in the beta position has been used for positron emission tomography studies of L-DOPA utilization in the brain. The brain uptake and kinetics of L-[11C]DOPA-derived radioactivity were studied in healthy male volunteers, and the specific utilization, i.e. decarboxylation rate of L-[11C]DOPA in different brain areas, was quantified using a brain region devoid of specific L-[11C]DOPA utilization as reference. Total uptake of L-[11C]DOPA-derived radioactivity measured in the brain varied two- to three-fold between subjects, with highest radioactivity in the striatal region. Specific utilization of L-[11C]DOPA radioactivity in the striatal region and in the prefrontal cortex varied twofold between subjects. No specific utilization was observed in other regions of the brain. The uptake of radioactivity in the brain increased dose-dependently with the simultaneous administration of unlabelled L-DOPA up to 10 mg. On the other hand, a decrease in brain radioactivity uptake was measured after pretreatment with 1 mg/kg oral L-DOPA, indicating competition for transport across the blood-brain barrier. Benserazide 0.5 mg/kg orally increased somewhat the radioactivity uptake to the brain. None of these pharmacological perturbations demonstrated any clearcut effect on specific utilization of L-[11C]DOPA. Thus, 11C-labelled L-DOPA is introduced as an alternative to the well-established L-6-[18F]fluoro-DOPA methodology in clinical studies on brain L-DOPA uptake and dopamine synthesis.

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Implantation of allogeneic pancreatic islets encapsulated in Millipore diffusion chambers has been reported to normalize the obese-hyperglycaemic syndrome in mice. In the present study, both young and adult ob/ob mice remained hyperglycaemic and gained weight after intrasplenic implantation of 500 isogeneic islets isolated from lean mice. Such islets normalized the elevated blood-glucose of alloxan-diabetic lean mice. Morphometric analysis of the intrasplenically implanted islets showed that the mean islet volume in the ob/ob mice was five times larger than that of the lean, non-diabetic mice. Immunocytochemical staining of the spleens showed an increased proportion of B-cells in the enlarged, intrasplenic islets in the ob/ob mice. Moreover, autoradiographical examination of these islets demonstrated the presence of several labelled cells. These results suggest that the growth of the implanted "lean" islets is due to extrapancreatic factors which stimulate islet cell replication in the obese-hyperglycaemic mouse.

The precursor of serotonin, L-5-hydroxytryptophan (L-5-HTP), was radiolabelled with 11C in the beta-position, yielding [beta-11C]serotonin after decarboxylation, allowing positron emission tomography studies of L-5-HTP uptake across the blood-brain barrier. We studied 8 healthy volunteers and 6 patients with histories of DSM-III major depression, 2 with repeated examinations after clinically successful treatment. We report a significantly lower uptake of [11C]5-HTP across the blood-brain barrier in depressed patients, irrespective of phase of illness. The findings emphasize that serotonin is involved in depressive pathophysiology and support earlier suggestions that the transport of 5-HTP across the blood-brain barrier is compromised in major depression.

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