Improved visual [(123)I]FP-CIT SPECT interpretation for evaluation of parkinsonism by visual rating of parametric distribution volume ratio images.

AIM: Imaging of presynaptic dopamine transporters (DAT) by single-photon emission computed tomography (SPECT) and [(123)I]FP-CIT is an established method for differentiating between neurodegenerative and non-neurodegenerative parkinsonism. Whereas a region-of-interest (ROI) analysis is the method of choice for analyzing [(123)I]FP-CIT SPECT studies, visual image interpretations can also provide highly accurate results. The present study was undertaken to validate a visual reading system for parametric volume of distribution (DVR) [(123)I]FP-CIT SPECT images that combines the quantitative nature of ROI analyses and the simplicity of visual readings. METHODS: A 9-step linear visual rating template for semi-quantitative DVR ratings of caudate nucleus and putamen was developed (VRDVR). The conventional 4-step visual reading system that is mainly based on the [(123)I]FP-CIT uptake pattern was used for comparison (VRP method). Six independent observers retrospectively rated the [(123)I]FP-CIT scans of 30 consecutive parkinsonism and tremor patients (N.=16 neurodegenerative, N.=14 non-neurodegenerative) using VRDVR and VRP. In addition, a highly trained investigator performed manual ROI analyses. RESULTS: The ROI analysis provided complete separation of both patient groups by comparing the lower DAT binding of both putamina (i.e., putamen contralateral to clinically most affected side in neurodegenerative parkinsonism). Using VRP, the two most experienced observers correctly classified all patients while 20 false-positive ratings occurred in the less experienced observers (mean area under the receiver operating characteristic curve [AUCROC] of all observers 0.93±0.07). The VRDVR ratings of the two most experienced observers did not overlap between patient groups, although at different VRDVR score cut-offs. Using the same VRDVR score cut-off for all observers, only six false-negative and one false-positive ratings occurred in total (AUCROC 0.99±0.01). Inter-observer agreement was good for VRP and VRDVR. Moreover, semi-quantitative VRDVR and quantitative ROI analyses showed a strong correlation in all observers (Spearman's rho, 0.85-0.91). CONCLUSIONS: The proposed VRDVR method offers a very promising visual analysis method for [(123)I]FP-CIT SPECT studies in parkinsonism. The accuracy of VRDVR readings was found to be superior to conventional VRP, while it provided a diagnostic accuracy in less experienced observers that is comparable to manual ROI analyses by a highly trained investigator.

Acute S-ketamine application does not alter cerebral [18F]altanserin binding: a pilot PET study in humans.

Modeling short-term psychotic states with subanaesthetic doses of ketamine provides substantial experimental evidence in support of the glutamate hypothesis of schizophrenia. Ketamine exerts its pharmacological effects both directly via interactions with glutamate receptors and indirectly by stimulating presynaptic release of endogenous serotonin (5-HT). The aim of this feasibility study was to examine whether acute ketamine-induced 5-HT release interferes with the binding of the 5-HT(2A) receptor (5-HT(2A)R) radioligand [(18)F]altanserin and positron emission tomography (PET). Two subjects treated with ketamine and one subject treated with placebo underwent [(18)F]altanserin PET at distribution equilibrium conditions. Robust physiological, psychopathological and cognitive effects were present at ketamine plasma concentrations exceeding 100 microg/l during >70 min. Notwithstanding, we observed stable radioligand binding (changes +/-95% CI of -1.0 +/- 1.6% and +4.1 +/- 1.8% versus -1.2 +/- 2.6%) in large cortical regions presenting high basal uptake of both, [(18)F]altanserin and ketamine. Marginal decreases of 4% of radioligand binding were observed in the frontal lobe, and 8% in a posteriorily specified frontomesial subregion. This finding is not compatible with a specific radioligand displacement from 5-HT(2A)R which should occur proportionally throughout the whole brain. Instead, the spatial pattern of these minor reductions was congruent with ketamine-induced increases in cerebral blood flow observed in a previous study using [(15)O]butanol PET. This may caused by accelerated clearance of unspecifically bound [(18)F]altanserin from cerebral tissue with increased perfusion. In conclusion, this study suggests that [(18)F]altanserin PET is not sensitive to acute neurotransmitter fluctuations under ketamine. Advantageously, the stability of [(18)F]altanserin PET towards acute influences is a prerequisite for its future use to detect sub-acute and chronic effects of ketamine.