The Binding of the High Affinity Radioligand Fallypride to the D2-dopamine Receptor is Sensitive to Injected Mass – a PET Study in Rodents

Purpose 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 [ 18 F]fallypride and [ 11 C]fallypride was injected in mice over a wide range of molar activity and the binding potential (BP) was compared. Procedures. Eight mice (C57BL/6 J) went through three PET measurements within two weeks. [ 11 C]fallypride with the highest possible molar activity (MA) and [ 18 F]fallypride with normal and lower molar activity (lowerMA). Results The binding of [ 11 C]fallypride was highest with a BP ND of 13.5 ± 1.1 BP ND . The binding of [ 18 F]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. Conclusion In this PET study in mice the average radioligand occupancy was estimated to 19% even for 11 C-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.