SYNTHESIS OF [C-11] PLATELET-ACTIVATING-FACTOR (PAF) ANALOGS FOR IN-VIVO IMAGING OF PAF RECEPTORS

1-O-Hexadecyl-2-O-N,N-dimethylcarbamoyl-sn-glycero-3-phosphocholine[choline methyl-C-11] ([C-11]dimethylcarbamoyl-PAF) and 1-O-Hexadecyl-2-O-acetyl-sn-glycero-3-phosphocholine[choline methyl-C-11] ([C-11]C-16 -PAF) were synthesized as follows; Each of non-labeled dimethylcarbamoyl-PAF and C-16-PAF was treated with sodium benzene thiolate to derive their desmethyl-precursors containing a dimethylphosphoethanolamine at sn-3 . C-11-Labeled dimethylcarbamoyl-PAF and C16-PAF were synthesized by methylation of the respective desmethyl-precursors using ([C]CH3I)-C-11. The radiochemical yield of methylation in [C-11]dimethylcarbamoyl-PAF and [C-11]C-16-PAF was about 15 and 10 % (decay corrected), respectively. The lower yield of [C-11]C-16-PAF compared with that of [C-11]dimethylcarbamoyl-PAF was attributed to hydrolysis of the 2-acetyl group of [C-11]C-16-PAF during methylation. To study the stability to enzymatic hydrolysis, [C-11]dimethylcarbamoyl-PAF or [C-11]C-16-PAF was incubated with mouse plasma at 37-degrees-C. [C-11]Dimethylcarbamoyl-PAF remained intact for 60 min. On the other hand, almost all the radioactivity of [C-11]C-16-PAF was converted into [C-11]C-16-lyso-PAF in 5 min. These observations indicate that [C-11]dimethylcarbamoyl-PAF can be a suitable probe for in vivo imaging of PAF receptors.