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

Abstract

A series of ergoline derivatives, analogues of Pergolide 1 and Lysergol 6, were synthesized, radiolabeled with '=I 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 SB-methylene) or at the 2-position of the indole portion of the ergoline moie Of the 8 radiolabeled compounds tested, two pergolide analogues, SB-(methyl%eseleno)-methyl-6-propyl ergoline 5 and 8B-['~I]-iodomethyl-6-propyl ergoline 2f 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 '=I may yield a clinically useful brain imaging radiopharmaceutical. 1 2 5 , 9 J [O;I H,,, C H 2 7 6 S e [ 4cH2c 2 z. cn,i