Synthesis of 11C/13C-labelled prostacyclins

A one-pot synthesis of (15R)-16-(3-[C-11]methylphenyl)-17,18,19,20-tetranorisocarbacyclin methyl ester was performed using a palladium-promoted reaction of [C-11]methyl iodide with ( 15R)-16-(3-tri-n-butylstannylphenyl)-17,18,19,20,-tetranorisocarbacyclin methyl ester. The C-15 epimer(l5S)-16-( 3-[C-11] methylphenyl)17,18,19,20-tetranorisocarbacyclin methyl ester was synthesised in the same way starting from (15S)-16-(3-tributylstannylphenyl)17,18,19,20-tetranorisocarbacyclin methyl ester. The decay-corrected radiochemical yields were 33-45% based on [C-11]methyl iodide produced, and the radiochemical purify of the product was > 95%. The total synthesis time was 35 min, counted from end of radionuclide production to product ready for administration. The C-11-labelled prostacyclin methyl esters were easily hydrolysed using sodium hydroxide affording the C-11-labelled prostacyclin acids in quantitative yields. The stereoisomers (15R)-16-(3-methylphenyl)-17,18,19,20-tetranorisocarbacyclin [C-11]methyl ester and (15S)-16-(3-methylphenyl)-17,18,19,20-tetranorisocarbacyclin [C-11]methyl ester were synthesised by esterification using [C-11]methyl iodide and the tetrabutylammonium salts of (15R)-16-(3-methylphenyl)-17,18,19,20-tetranorisocarbacyclin acid and (15S)-16-(3-methylphenyl)-17, 18,19,20-tetranorisocarbacyclin acid, respectively. The decay-corrected radiochemical yields were in the range of 55% counting from [C-11]methyl iodide produced, and the radiochemical purity of the product was > 95%. The total synthesis time was 35 min, counting from end of radionuclide production to product ready for administration. Both of these labelling methods can be used for labelling with C-13 when (C-13)methyl iodide is used. The methods described herein have already proved important since they enable the in vivo use of PET to study the action of prostacyclins in the brain.