Imaging the cerebral serotonin 2A (5-HT2A ) receptors with positron emission 
tomography (PET) has been carried out in humans with [(11) C]MDL 100907 and 
[(18) F]altanserin. Recently, the MDL 100907 analogue [(18) F]MH.MZ was 
developed combining the selectivity profile of MDL 100907 and the favourable 
radiophysical properties of fluorine-18. Here, we present a direct comparison of 
[(18) F]altanserin and [(18) F]MH.MZ. 5-HT2A receptor binding in pig cortex and 
cerebellum was investigated by autoradiography with [(3) H]MDL 100907, [(18) 
F]MH.MZ, and [(18) F]altanserin. [(18) F]MH.MZ and [(18) F]altanserin were 
investigated in Danish Landrace pigs by brain PET scanning at baseline and after 
i.v. administration of blocking doses of ketanserin. Full arterial input 
function and high performance liquid chromatography (HPLC) analysis allowed for 
tissue-compartment kinetic modeling of PET data. In vitro autoradiography showed 
high binding in cortical regions with both [(18) F]MH.MZ and [(18) F]altanserin. 
Significant 5-HT2A receptor binding was also found in the pig cerebellum, thus 
making this region unsuitable as a reference region for in vivo data analysis in 
this species. The cortical binding of [(18) F]MH.MZ and [(18) F]altanserin was 
blocked by ketanserin supporting that both radioligands bind to 5-HT2A receptors 
in the pig brain. In the HPLC analysis of pig plasma, [(18) F]MH.MZ displayed a 
fast and reproducible metabolism resulting in hydrophilic radiometabolites only 
whereas the metabolic profile of [(18) F]altanserin as expected showed 
lipophilic radiometabolites. Due to the slow kinetics of [(18) F]MH.MZ in 
high-binding regions in vivo, we suggest that [(18) F]MH.MZ will be an 
appropriate tracer for low binding regions where kinetics will be faster, 
whereas [(18) F]altanserin is a suitable tracer for high-binding regions.