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Background: Carriers of the Huntington disease (HD) mutation develop a progressive neurodegenerative disorder after a pre-clinical phase. We examined the value of 11C-raclopride PET (RAC) as a biomarker for pre-clinical HD pathophysiology. Methods: In a prospective cohort study with clinical and neuropsychological assessment we collected complete RAC data in 18 pre-clinical mutation carriers (HD-PMC) and 11 controls. Follow-up was 2 years. We calculated striatal RAC binding potential (BP) to measure dopamine D2 receptor availability. Results: No HD-PMC had overt neuropsychological dysfunction. RAC-BP in putamen was abnormal in up to 44% of HD-PMC. The rate of RAC-BP decline (2.6% per year) was not significantly higher than in controls. Follow-up putaminal BP correlated weakly with predicted distance to onset of clinical HD ( P = 0.034), but the rate of decline did not. Three HD-PMC developed motor abnormalities suspect for HD but did not show an increased rate of decline of putaminal BP. Conclusions: Many HD-PMC have striatal abnormalities but we found no clearly increased rate of D2 receptor changes around the onset of clinical HD. A longer follow-up of the present study cohort is needed to establish the value of RAC-BP in assessing the risk of clinical conversion from striatal D2 binding data. [ABSTRACT FROM AUTHOR]

Mutations in the DJ-1 gene lead to autosomal recessive early-onset parkinsonism. We performed F-DOPA and FDG PET neuroimaging in two parkinsonism patients homozygous for DJ-1 mutations, three relatives heterozygous for a DJ-1 mutation and one non-carrier, all from the originally described kindred from The Netherlands. Their characteristics were compared to those of typical Parkinson’s disease patients and healthy controls. Both parkinsonism patients had reduced F-DOPA uptake concordant with typical Parkinson’s disease. In the, clinically unaffected, heterozygous relatives, F-DOPA metabolism was unremarkable, thus not suggesting a dosage effect of the DJ-1 gene. [ABSTRACT FROM AUTHOR]

Pharmacokinetic modelling of radiotracers for positron emission tomography (PET) imaging of neuroreceptors can be performed with time-activity data for brain and blood. We aimed to develop an alternative to withdrawal of arterial blood samples for acquisition of a blood curve. A supportive primate chair was constructed out of styrofoam and fixed to the head portion of the bed of a PET scanner. A lightly anaesthetised rhesus monkey was positioned in the chair in a sitting position and injected with the radiotracer. The styrofoam chair provided sufficient support for the monkey. The presence of the chair in the PET scanner caused negligible attenuation of radiation, allowing simultaneous acquisition of dynamic data from the subject's brain and heart. We conclude that a styrofoam primate chair is an ideal tool to measure blood and brain data from a rhesus monkey with PET. Invasiveness to the animal is reduced, as well as experimenter time. [ABSTRACT FROM AUTHOR]

Tobacco smoking is the most frequent form of substance abuse. Several studies have shown that the addictive action of nicotine is mediated by the mesolimbic dopamine system. This system is implicated in reward processing. In order to better understand the relationship between nicotine addiction and reward in humans, we investigated differences between smokers and nonsmokers in the activation of brain regions involved in processing reward information. Using [H215O] positron emission tomography (PET), we measured regional cerebral blood flow (rCBF) in healthy smokers and nonsmokers while they performed a prelearned, pattern-recognition task. We compared two conditions involving nonmonetary reinforcement or monetary reward with a baseline condition in which nonsense feedback was presented. With monetary reward, we found activation in the frontal and orbitofrontal cortex, occipital cortex, cingulate gyrus, cerebellum, and midbrain in both groups. Additionally, monetary reward activated typical dopaminergic regions such as the striatum in nonsmokers but not in smokers. We found a similar pattern of activation associated with nonmonetary reinforcement in nonsmokers, whereas activation was found in smokers only in the cerebellum. The different patterns of activation suggest that the brains of smokers react in a different way to reward than those of nonsmokers. This difference involves in particular the regions of the dopaminergic system including the striatum. In principle these observations could be interpreted either as a consequence of tobacco use or as a primitive condition of the brain that led people to smoke. Supported by related nonimaging studies, we interpret these differences as a consequence of tobacco smoking, even if a short-term effect of smoking prior to the experiment cannot be excluded. [ABSTRACT FROM AUTHOR]

This article reviews possible clinical applications of positron emission tomography (PET) in patients with CNS lymphomas. PET allows quantitative assessment of brain tumor pathophysiology and biochemistry in vivo. Therefore, it provides different information about tumors when compared to histological or neuroradiological methods. In a diagnostic setting, PET cannot differentiate between primary lymphomas of the CNS, brain secondaries, or malignant gliomas, since various brain tumors share biochemical alterations. In HIV patients with contrast-enhancing brain tumors, however, data from the literature suggest that PET with the tracer F-18 fluoro-deoxyglucose may help to discriminate neoplastic (CNS lymphoma) from inflammatory (e.g. toxoplasmosis) lesions. Assuming that tumor biochemistry is highly abnormal in the most malignant parts of tumors, PET may also assist in defining targets for stereotactic biopsy. With regard to treatment evaluation, the prediction of individual treatment response is among the most challenging clinical applications of PET. On the one hand, this could be achieved on the basis of measures like tumor perfusion, oxygen consumption, or hypoxia. On the other hand, PET tracer methods may allow to quantify the expression of gene products following gene therapy. However, in CNS lymphoma patients these topics have yet not been addressed with PET. [ABSTRACT FROM AUTHOR]

We studied a patient with juvenile pilocytic astrocytoma (JPA) using positron emission tomography (PET), 18 F-fluorodeoxyglucose (FDG),11 C-methionine (MET), and 82Rubidium (RUB). Non-linear fitting and multiple time graphical plotting of the dynamic PET data revealed values for tumor plasma volume, blood-brain barrier transport rate constants and tracer distribution volume in the range of glioblastomas and meningiomas, or higher. Likewise, the steady-state accumulation of MET and FDG was increased. With regard to the known vascular composition of JPA, our data suggest that increased transport and distribution considerably contribute to the high net tracer uptake observed in this tumor. [ABSTRACT FROM AUTHOR]