11C-labelling of substance P. Preparation of a homocysteine-containing precursor and its subsequent application in the synthesis of the labelled neuropeptide

Abstract

The synthesis of a useful [Hcy¹¹]Substance P derivative (16), containing only two protecting groups both labile to sodium in liquid ammonia, by a multistep [3 +(4 + 4)] strategy in solution, is reported. This approach furnished solid intermediates in high yields. After removal of the protecting groups, the product was selectively methylated on sulphur in situ with the aid of [¹¹C]methyl iodide as previously described for Met-enkephalin to give [S-methyl-¹¹C] Substance P (18) in a radiochemical yield of 35%. The total time of preparation was 45–60 min from the start of the synthesis of [¹¹C]methyl iodide. After purification by h.p.l.c., the peptide exhibited a radiochemical purity higher than 98%. An intermediary Substance P_4–11 fragment was also labelled.