The synthesis of [26,27-C-11]dihydroxyvitamin D-3, a tracer for positron emission tomography (PET)

1 alpha ,25-Dihydroxyvitamin D-3, an endogenous ligand with the highest aff inity for the vitamin D receptor (VDR), was labeled with C-11 for use in bi ological experiments. The radionuclide was incorporated via the reaction of [C-11]methyllithium on a methyl ketone precut-sot, in tetrahydrofuran at - 10 degreesC. Deprotection of the labeled intermediate yielded 2.5-3 GBq [26 ,27-C-11]1 alpha ,25-dihydroxyvitamin D-3 [C-11-1,25(OH)(2) D-3] with speci fic radioactivity averaging 100 GBq/mu mol at the end of synthesis and HPLC purification. The entire process took 48 min from the end of radionuclide production. In vitro binding experiments in rachitic chick purified VDR dem onstrated the high affinity binding of this novel tracer. Thus., C-11-1,25( OH)(2) D-3 is available for in vivo distribution studies and may be suitabl e for the positron emission tomography (PET) determination of VDR levels an d occupancy in animals and humans. (C) 2001 Elsevier Science Ltd. All right s reserved.