The Binding of the High Affinity Radioligand Fallypride to the D2-dopamine Receptor is Sensitive to Injected Mass - a...

Fallypride is a widely used high affinity radioligand for quantification of D2-dopamine receptor binding in small animal PET imaging. To examine the effect of mass both [¹⁸F]fallypride and [¹¹C]fallypride was injected in mice over a wide range of molar activity and the binding potential (BP) was compared.

Eight mice (C57BL/6 J) went through three PET measurements within two weeks. [¹¹C]fallypride with the highest possible molar activity (MA) and [¹⁸F]fallypride with normal and lower molar activity (lowerMA).

The binding of [¹¹C]fallypride was highest with a BP_ND of 13.5 ± 1.1 BP_ND. The binding of [¹⁸F]fallypride was lower, 8.6 ± 2.2 BP_ND in the normal condition and 5.3 ± 1.3 BP_ND at the lowerMA condition. By consequence, BP_ND showed a strong negative correlation with injected mass (R2 = 0.95, P < 0.05). Binding data were entered in a Scatchard analysis yielding a B_max of 62 pmol/g and a K_D of 0.25 nM.

In this PET study in mice the average radioligand occupancy was estimated to 19% even for ¹¹C-labeled fallypride despite the high MA of 153.3 GBq/µmol and low injected mass of 0.03 µg. Therefore, high affinity radioligands should be applied with care in small animal PET studies and radiochemistry has to be at its best to assure that tracer conditions are met in small animal imaging PET imaging.