期刊
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
卷 46, 期 10, 页码 2051-2064出版社
SPRINGER
DOI: 10.1007/s00259-019-04369-6
关键词
P2X7 receptor; Neuroinflammation PET; Parkinson; Dosimetry; Genotyping; [C-11]JNJ54173717
资金
- Michael J. Fox Foundation [12062]
PurposeThe P2X7 receptor (P2X7R) is an ATP-gated ion channel predominantly expressed on activated microglia and is important in neurodegenerative diseases including Parkinson's disease (PD). In this first-in-human study, we investigated [C-11]JNJ54173717 ([C-11]JNJ717), a selective P2X7R tracer, in healthy volunteers (HV) and PD patients. Biodistribution, dosimetry, kinetic modelling and short-term test-retest variation (TRV), as well as possible genotype effects, were investigated.MethodsBiodistribution and radiation dosimetry studies were performed in threeHV (mean age 302years, two women) using whole-body PET/CT. The most appropriate kinetic model was determined in 11HV (mean age 6210years, six women) and 10 PD patients (mean age 64 +/- 8years, three women; mean UPDRS motor score 21 +/- 8) using 90-min dynamic simultaneous PET/MR scans. The total volume of distribution (V-T) was calculated using a one-tissue and a two-tissue compartment model (1TCM, 2TCM) and Logan graphical analysis, and its time stability was assessed. Seven subjects underwent retest scans (mean age 60 +/- 13years, fourHV, one woman). A group analysis was performed to compare PD patients and HV. Finally, 13 exons of P2X7R were genotyped in all subjects included in the second part of the study.Results The mean effective dose was 4.47 +/- 0.32 mu Sv/MBq, with the highest absorbed doses to the gallbladder, liver and small intestine. A reversible 2TCM was the most appropriate kinetic model with relatively homogeneous V-T values in the grey and white matter. Average V-T values were 3.4 +/- 0.8 in HV and 3.3 +/- 0.7 in PD patients, with no significant difference between the groups, but a possible genotype effect (rs3751143) was identified which can affect V-T. Average TRV was 10-15%. The stability of V-T over time allowed a reduction in scan time to 70min.Conclusion [C-11]JNJ717 is safe and suitable for quantifying P2X7R expression in human brain. In this pilot study, no significant differences in P2X7R binding were found between HV and PD patients. The results also suggest that genotype effects need to be incorporated in future P2X7R PET analyses.
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