Suitability of [18F]Altanserin and PET to Determine 5-HT2A Receptor Availability in the Rat Brain: In Vivo and In Vitro Validation of Invasive and Non-Invasive Kinetic Models

Purpose

While the selective 5-hydroxytryptamine type 2a receptor (5-HT_2AR) radiotracer ¹⁸F]altanserin is well established in humans, the present study evaluated its suitability for quantifying cerebral 5-HT_2ARs with positron emission tomography (PET) in albino rats.

Procedures

Ten Sprague Dawley rats underwent 180 min PET scans with arterial blood sampling. Reference tissue methods were evaluated on the basis of invasive kinetic models with metabolite-corrected arterial input functions. In vivo 5-HT_2AR quantification with PET was validated by in vitro autoradiographic saturation experiments in the same animals.

Result

Overall brain uptake of ¹⁸F]altanserin was reliably quantified by invasive and non-invasive models with the cerebellum as reference region shown by linear correlation of outcome parameters. Unlike in humans, no lipophilic metabolites occurred so that brain activity derived solely from parent compound. PET data correlated very well with in vitro autoradiographic data of the same animals.

Conclusion

¹⁸F]Altanserin PET is a reliable tool for in vivo quantification of 5-HT_2AR availability in albino rats. Models based on both blood input and reference tissue describe radiotracer kinetics adequately. Low cerebral tracer uptake might, however, cause restrictions in experimental usage.