Characterization of [<sup>11</sup>C]Lu AE92686 as a PET radioligand for phosphodiesterase 10A in the nonhuman primate brain.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27817159.
- Also identified by DOI 10.1007/s00259-016-3544-9 and PMC identifier 5215309.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
[<sup>11</sup>C]Lu AE92686 is a positron emission tomography (PET) radioligand that has recently been validated for examining phosphodiesterase 10A (PDE10A) in the human striatum. [<sup>11</sup>C]Lu AE92686 has high affinity for PDE10A (IC <sub>50</sub> = 0.39 nM) and may also be suitable for examination of the substantia nigra, a region with low density of PDE10A. Here, we report characterization of regional [<sup>11</sup>C]Lu AE92686 binding to PDE10A in the nonhuman primate (NHP) brain. A total of 11 PET measurements, seven baseline and four following pretreatment with unlabeled Lu AE92686 or the structurally unrelated PDE10A inhibitor MP-10, were performed in five NHPs using a high resolution research tomograph (HRRT). [<sup>11</sup>C]Lu AE92686 binding was quantified using a radiometabolite-corrected arterial input function and compartmental and graphical modeling approaches. Regional time-activity curves were best described with the two-tissue compartment model (2TCM). However, the distribution volume (V <sub>T</sub>) values for all regions were obtained by the Logan plot analysis, as reliable cerebellar V <sub>T</sub> values could not be derived by the 2TCM. For cerebellum, a proposed reference region, V <sub>T</sub> values increased by ∼30 % with increasing PET measurement duration from 63 to 123 min, while V <sub>T</sub> values in target regions remained stable. Both pretreatment drugs significantly decreased [<sup>11</sup>C]Lu AE92686 binding in target regions, while no significant effect on cerebellum was observed. Binding potential (BP <sub>ND</sub>) values, derived with the simplified reference tissue model (SRTM), were 13-17 in putamen and 3-5 in substantia nigra and correlated well to values from the Logan plot analysis. The method proposed for quantification of [<sup>11</sup>C]Lu AE92686 binding in applied studies in NHP is based on 63 min PET data and SRTM with cerebellum as a reference region. The study supports that [<sup>11</sup>C]Lu AE92686 can be used for PET examinations of PDE10A binding also in substantia nigra.
Medical subject headings
- Brain
- Molecular Imaging
- Phosphoric Diester Hydrolases
- Positron-Emission Tomography
- Pyridines
- Triazoles