PET analysis of central [¹¹ C]raclopride binding in healthy young adults and schizophrenic patients—reliability and age effects

Abstract

Central D2-dopamine receptor occupancy determined by positron emission tomography (PET) during neuroleptic drug treatment may be a useful measure for optimal dose finding in schizophrenic patients. The clinical benefit is dependent on the reliability of such determinations. The ratio of radioactivity in the striatum to that of the cerebellum 1s widely used for calculation of D2-receptor occupancy and as an index of D2-dopamine receptor density. To test the reliability of such ratios a test-retest analysis was performed in a series of healthy subjects.The reliability was very high, both when experiments were repeated on the same day and after time intervals of months to years. A group of subjects were examined twice using PET camera systems with different resolution.The strialuni to cerebellum ratios obtained from the high-resolution PET camera system were significantly higher than ratios from the camera with lower resolution. The age effect on the striatum to cerebellum ratio was examined in 25 healthy young adults and in 18 neuroleptic-naive schizophrenic patients. A statistically significant decline was found both in the healthy controls and in the schizophrenic patients. The results do not support the view that there is a lack of age effect on the D2-dopamine receptor density in schizophrenia.

Effects of Blood Flow on [11C]Raclopride Binding in the Brain: Model Simulations and Kinetic Analysis of PET Data

“…= 0.51, k4 = 0.14) with k31k4 = 3.68, which is very close to the values reported here (Brnax'IKd/)' They could not, however, assess reproducibility since their second studies were at low specific activity. Reproducibility of raclopride binding as determined by the ratio of integrated radioactivities (from 21 to 33 min) for putamen to CB has been reported by Nordstrom et al (1992). The mean of the ratio of the integrated radioactivities of putamen to CB from study 2 (retest) to study 1 (test) was found to be 1.01 with an SD of 0.07, which is similar to the repro ducibility of DV ratios reported by Volkow et al (1993a) and to Brnax'IKd' values reported here.…”

Changes in striatal D2-receptor density following chronic treatment with amphetamine as assessed with pet in nonhuman primates

“…However, it is reasonable to assume that the reliability is comparable to the high reliability (5.8%, n ϭ 6) observed in humans . The monkey brain is smaller but the 3D-PET-system used in the present study has higher resolution, 3.7 mm FWHM (Wienhard et al, 1994), than the old system, Scanditronix PC-384-7B, 8.5 mm FWHM (Litton et al, 1984), used in the human study by Nordström et al (1992). Furthermore, the assumption of a similarly low test-retest variability in the determination of B max in humans and intact monkeys is indirectly supported by a recent PET study performed in our center (Ginovart et al, 1997).…”

Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers

“…41,42 To achieve comparable results for the two different PET systems, B/Fratios obtained with the Scanditronix 384-7B were multiplied by 1.14 according to a previously published comparative study. 32 To avoid a possible influence from dopamine D3 receptors in the nucleus accumbens the ventral striatum was not included in the region of interest.…”