W e describe here t h e synthesis of twoC1lC-methylJlabelled analogs of choline and the influence of t h e solvent, addition of a base, and reaction t i m e on t h e radiochemical yield.
The reactions produced equally good yields in methanol and acetonitrile and r e a f p d maximum radiochemical yield at about 5-10 min. The addition of a base in t h e case of C C-~nethyl]pyrroli~ipcholine increases t h e radiochemical y i e l h Optimum radiochemical yields were 30% for[ C-methyllpiperidinocholine and 40% foL[ C-methy1lpyrrolidinocholine for t w o choline analogs.
KEY WORDiji 'C-labelling, C 11 Clpyrrolidinocholine, fl 'C@iperidinocholine, C-labelled choline analogs.
XNTRODUCTION
An alteration in t h e synthesis of acetylcholine has been postulated to affect t h e development and progression of Alzheimer's disease (1 ,Z). Two distinct choline-uptake mechanisms (high and low affinity uptake) have been described. We surmised t h a t t h e high affinity choline uptake system in human brain might be scanned using llC-labelled choline and positron emission tomography (PET). Friedland et a1 (3) attempted to scan this high affinity uptake system in monkey and Gauthier et a1 (4) in humans using?'C-methyl]choline.
Unfortunately the results were unsatisfactory because of large amounts of endogenous choline used in t h e synthesis of acetylcholine. This prompted us to investigate t h e choline analogs, pyrrolidinochline and piperidinocholine, because they a r e taken up by t h e same system as acetylcholine and are substrates for acetylcholine esterase (5).
1 1
We have described the synthesis of no-carrier-added[ C-methyl]choline elsewhere (6), and other researchers recently investigated t h e e f f e c t of a possible impurity, 2-(N,Ndimethyl) ethanol, on the uptake of choline by the r a t brain (7). Here we describe the synthesis of no-carrier-added I 'C-labelled (methyl) analogs of choline, piperidynocholine and pyrrolidinocholine. The synthesis is based on t h e s a m e principle as that described earlier by us (6) and reported recently (7) for[ C-methyocholine.