RESUMEN
UNLABELLED: The cocaine analog 2 beta-carbomethoxy-3 beta-[4-iodophenyl]tropane (beta-CIT) labeled with 11C was used to study dopamine reuptake sites with PET. METHODS: Three normal subjects and nine patients with Parkinson's disease were investigated. Each of them underwent a dynamic PET scan (25 timeframes over 80 min) with [11C]-beta-CIT. A dose of 102.5-211.3 MBq (2.77-5.71 mCi) of this ligand was administered intravenously and a PET examination with an ECAT 931/08 PET camera was carried out. Ratios between the striatal/cortical/thalamic/midbrain and cerebellar uptake of this radioligand were calculated. RESULTS: The highest accumulation of [11C]beta-CIT was observed in the caudate and putamen, though there was some uptake in the thalamus and the midbrain. Cortical uptake was negligible. Carbon-11-beta-CIT accumulated significantly less in the putamen of the Parkinson's patients than in the normal subjects. The putamen-to-cerebellum ratio in the Parkinson's patients was 1.59 +/- 0.04 and 1.80 +/- 0.13s (p = 0.028) in the normal subjects. In the caudate, there was no significant difference between the Parkinson's patients and the normal subjects. CONCLUSION: These results imply that [11C]beta-CIT is a useful compound for carrying out a PET examination of the function of the presynaptic monoaminergic neurons both in normal and pathological brains.
Asunto(s)
Encéfalo/metabolismo , Radioisótopos de Carbono , Cocaína/análogos & derivados , Dopamina/metabolismo , Enfermedad de Parkinson/metabolismo , Tomografía Computarizada de Emisión , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Núcleo Caudado/diagnóstico por imagen , Núcleo Caudado/metabolismo , Cerebelo/diagnóstico por imagen , Cerebelo/metabolismo , Femenino , Humanos , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/tratamiento farmacológico , Putamen/diagnóstico por imagen , Putamen/metabolismo , Serotonina/metabolismo , Tálamo/diagnóstico por imagen , Tálamo/metabolismoRESUMEN
UNLABELLED: PET studies were carried out on brain dopamine D1 receptors using two new ligands, [11C]SCH 39166 and [11C]NNC 756. METHODS: Four normal subjects and eight predominantly unilateral patients with early Parkinson's disease were investigated. Each of them underwent both a PET scan with [11C]SCH 39166 and one with [11C]NNC 756. A dose of about 185 MBq (5 mCi) of these ligands was administered intravenously and a dynamic PET scan with an ECAT 931/08 PET camera was carried out. Ratios between the striatal and cerebellar uptake of these compounds were calculated. RESULTS: Both [11C]SCH 39166 and [11C]NNC 756 accumulated in the striatum. There was also some neocortical binding; 75% of the striatal value in the case of [11C]SCH 39166 and 60% with [11C]NNC 756 which displayed higher (p < 0.01) uptake in the striatum than [11C]SCH 39166. There were no significant side-to-side differences in the controls nor in the parkinsonian patients. CONCLUSIONS: These results imply that both [11C]SCH 39166 and [11C]NNC 756 can be used in PET studies for the visualization and quantification of dopamine D1 receptors. Since [11C]NNC 756 has a significantly better signal-to-noise ratio in the striatum than [11C]SCH 39166, it seems to offer definite advantages for studies of D1 receptors.
Asunto(s)
Benzazepinas , Benzofuranos , Encéfalo/diagnóstico por imagen , Antagonistas de Dopamina , Enfermedad de Parkinson/diagnóstico por imagen , Receptores de Dopamina D1/análisis , Tomografía Computarizada de Emisión/métodos , Adulto , Anciano , Benzazepinas/metabolismo , Benzazepinas/farmacocinética , Benzofuranos/metabolismo , Benzofuranos/farmacocinética , Encéfalo/metabolismo , Radioisótopos de Carbono , Femenino , Humanos , Cinética , Masculino , Persona de Mediana Edad , Especificidad de Órganos , Enfermedad de Parkinson/metabolismo , Receptores de Dopamina D1/metabolismo , Valores de ReferenciaRESUMEN
The effect of peripheral catechol-O-methyltransferase (COMT) inhibition with entacapone on striatal uptake of 6-[18F]fluoro-L-dopa (FDOPA) was studied with PET both without and with entacapone in fifteen advanced parkinsonian patients and six healthy controls. Entacapone significantly enhanced the fraction of unmetabolized FDOPA in plasma from 16% to about 50% at 80 minutes after FDOPA injection in all subjects. The striatal to occipital ratios and the striatal FDOPA uptake, expressed as a modified decarboxylation coefficient (k3R0), was significantly increased in healthy controls, whereas in parkinsonian patients the increase was significant only in the caudate. On the other hand, the influx constant (Ki) decreased significantly in the caudate and putamen in parkinsonian patients; in healthy controls the Ki remained virtually unchanged. Effective peripheral COMT inhibition markedly increased the fraction of FDOPA in plasma and thus its availability in the brain for decarboxylation both in patients and control subjects. However, the change in striatal FDOPA uptake was modest in the advanced parkinsonian patients as compared to that in control subjects, because of the advanced disease, decreased storage capacity, or both.