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

1Alpha,25-dihydroxyvitamin D(3), an endogenous ligand with the highest affinity for the vitamin D receptor (VDR), was labeled with 11C for use in biological experiments. The radionuclide was incorporated via the reaction of [11C]methyllithium on a methyl ketone precursor in tetrahydrofuran at -10 degrees C. Deprotection of the labeled intermediate yielded 2.5-3 GBq [26,27-11C]1alpha,25-dihydroxyvitamin D(3) [11C-1,25(OH)(2) D(3)] with specific radioactivity averaging 100 GBq/micromol 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 demonstrated the high affinity binding of this novel tracer. Thus; 11C-1,25(OH)(2) D(3) is available for in vivo distribution studies and may be suitable for the positron emission tomography (PET) determination of VDR levels and occupancy in animals and humans.