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Abstract: Positron emission tomography (PET) with [11C]raclopride is widely used to investigate temporal changes in the dopamine D2 receptor system attributed to the dopamine release. The simplified reference tissue model (SRTM) can be used to determine the binding potential (BPND) value using the time–activity curve (TAC) of the reference region as input function. However, in assessing temporal changes in BPND using the SRTM, multiple [11C]raclopride PET scans are required, and a second scan must be performed after the disappearance of the [11C]raclopride administered in the first scan. In this study, we have developed an extended multiple-injection SRTM to estimate the BPND change, from a single PET scan with multiple injections of [11C]raclopride, and we have validated this approach by performing numerous simulations and studies on monkeys. In the computer simulations, TACs were generated for dual injections of [11C]raclopride, in which binding conditions changed during the scans, and the BPND values before, and after, the second injection were estimated by the proposed method. As a result, the reduction in BPND was correlated, either with the integral of released dopamine, or with the administered mass of raclopride. This method was applied to studies on monkeys, and was capable of determining two identical BPND values when there were no changes in binding conditions. The BPND after the second injection decreased when binding conditions changed due to an increase in administered raclopride. An advantage of the proposed method is the shortened scan period for the quantitative assessment of the BPND change for neurotransmitter competition studies. [Copyright &y& Elsevier]

Abstract: A new method has been developed for diffusible tracers, to quantify CBF at rest and after pharmacological stress from a single session of dynamic scans with dual bolus administration of a radiotracer. The calculation process consisted of three steps, including the procedures of incorporating background radioactivity contaminated from the previous scan. Feasibility of this approach was tested on clinical SPECT studies on 16 subjects. Two sequential SPECT scans, 30 min apart, were carried out on each subject, after each of two split-dose administrations of 111 MBq IMP. Of these, 11 subjects received acetazolamide at 10 min before the second IMP injection. Additional PET scans were also carried out on 6 subjects on a separate day, at rest and after acetazolamide administration. The other 5 subjects were scanned only at rest during the whole study period. Quantitative CBF obtained by this method was in a good agreement with those determined with PET (y(ml/100 g/min)=1.07×(ml/100 g/min)−1.14, r =0.94). Vasareactivity was approximately 40% over the whole cerebral area on healthy controls, which was consistent with a literature value. Reproducibility of CBF determined in the rest–rest study was 1.5±5.7%. Noise enhancement of CBF images, particularly the second CBF, was reduced, providing reasonable image quality. Repeat assessment of quantitative CBF from a single session of scans with split-dose IMP is accurate, and may be applied to clinical research for assessing vascular reactivity in patients with chronic cerebral vascular disease. [Copyright &y& Elsevier]

Abstract: The aim of this study was to establish kinetic analysis of [5-11C-methoxy]donepezil ([11C]donepezil), which was developed for the in-vivo visualization of donepezil binding to acetylcholinesterase (AChE) using positron emission tomography (PET). Donepezil is an AChE inhibitor that is widely prescribed to ameliorate the cognitive impairment of patients with dementia. Six healthy subjects took part in a dynamic study involving a 60-min PET scan after intravenous injection of [11C]donepezil. The total distribution volume (tDV) of [11C]donepezil was quantified by compartmental kinetic analysis and Logan graphical analysis. A one-tissue compartment model (1TCM) and a two-tissue compartment model (2TCM) were applied in the kinetic analysis. Goodness of fit was assessed with χ 2 criterion and Akaike''s Information Criterion (AIC). Compared with a 1TCM, goodness of fit was significantly improved by a 2TCM. The tDVs provided by Logan graphical analysis were slightly lower than those provided by a 2TCM. The rank order of the mean tDVs in 10 regions was in line with the AChE activity reported in a previous post-mortem study. Logan graphical analysis generated voxel-wise images of tDV, revealing the overall distribution pattern of AChE in individual brains. Significant correlation was observed between tDVs calculated with and without metabolite correction for plasma time–activity curves, indicating that metabolite correction could be omitted. In conclusion, this method enables quantitative analysis of AChE and direct investigation of the pharmacokinetics of donepezil in the human brain. [Copyright &y& Elsevier]