To study the 5-HT(2A) receptors in the living human brain, using positron 
emission tomography (PET), two selective radiotracers are currently in use: 
[(18)F]altanserin and [(11)C]MDL 100907. It is, however, currently unknown to 
what extent data obtained with either tracer are directly comparable. The aim of 
this study was to compare binding characteristics of these two radiotracers in 
rat brain with respect to affinity (K(d)), receptor binding density (B(max)), 
binding potential (BP), and nonspecific binding. Further, binding kinetics, 
sensitivity towards competition with the endogenous transmitter serotonin, and 
the competitive/noncompetitive interaction between the two radioligands were 
evaluated. In addition, the selectivity of [(18)F]altanserin for the 5-HT(2A) 
receptor was assessed. The K(d) value of [(18)F]altanserin and [(3)H]MDL 100907 
was in the order of 0.3 nM. B(max) in frontal cortex was 523 and 527 fmol/mg 
protein, respectively. The binding of [(18)F]altanserin was not influenced by 
blocking either the 5-HT(2B/2C) or the alpha(1)-adrenergic receptors. At 37 
degrees C the association t(1/2) was 2.8 and 2.7 min and the dissociation t(1/2) 
was 11 and 13.5 min for [(18)F]altanserin and [(3)H]MDL 100907, respectively. 
Both radioligands were displaced by 5-HT, only at high concentrations; the K(i) 
value of 5-HT ranging between 650 and 3,300 nM. This indicates that binding of 
both radioligands in PET studies is not directly influenced by changes in 
endogenous 5-HT.Overall, the binding of [(18)F]altanserin and [(3)H]MDL 100907 
to the 5-HT(2A) receptor was very comparable, showing selective high affinity 
binding in the subnanomolar range.