Structure biodistribution relationship of radiolabeled ergolines: search for brain imaging radiopharmaceuticals

A series of ergoline derivatives, analogues of Pergolide and Lysergol were synthesized, radiolabeled with 125I or 75Se, and evaluated for their ability to cross the Blood Brain Barrier of rats, for potential use as radiopharmaceuticals for imaging the brain. Introduction of the radiolabel was either at the 17- position (attached to the 8β-methylene) or at the 2- position of the indole portion of the ergoline moiety. Of the 8 radiolabeled compounds tested, two pergoline analogues, 8β-(methyl-75Se-seleno)-methyl-6-propyl ergoline and 8β-[125I]-iodomethyl-6-propyl ergoline, showed the highest uptake in the brain, adrenal and heart with good organ to blood ratios. This work has shown that analogues of pergolide, a dopamine agonist, if labeled with 123I may yield a clinically useful brain imaging radiopharmaceutical. (author)