Radiolabeling and in vivo evaluation of [11C]AGH-44: a potential lead structure to develop a positron emission tomography radioligand for the 5-HT7 receptor
- 41 Downloads
AGH-44 is described as a selective low-basicity serotonin 7 receptor (5-HT7R) agonist. In this paper, we evaluate if AGH-44 can act as a lead structure to develop a 5-HT7R selective positron emission tomography (PET) tracer. 11C-labeling of AGH-44 succeeded in a two-step, one-pot procedure in good yields. Subsequent PET studies showed that [11C]AGH-44 displays low blood–brain-barrier passage in Long–Evans rats. Moreover, [11C]AGH-44 brain accumulation showed to be independent on permeability glycoprotein (P-gp) efflux inhibition. Results from biodistribution and metabolism studies could neither explain the observed low brain uptake. As such, we believe that this scaffold is not an optimal starting point to develop a 5-HT7R selective PET tracer.
KeywordsAGH-44 5-HT7 PET Carbon-11
The authors wish to thank the staff at the PET and Cyclotron unit for expert technical assistance.
- 14.Herth M et al (2014) Development of a novel 11C-labelled SB-269970 derivative for imaging the cerebral 5-HT7 receptors. J Nucl Med 55(supplement 1):1814Google Scholar
- 15.Keller SH et al (2016) Quantification accuracy of a new HRRT high throughput rat hotel using transmission-based attenuation correction: a phantom study. In: Nuclear science symposium, medical imaging conference and room-temperature semiconductor detector workshop (NSS/MIC/RTSD), 2016, IEEEGoogle Scholar