Synthesis and biodistribution studies of [I-125]-iodoergoline derivatives

The relatively high uptake in rat and dog brains of [Se-75]-Selenopergolide reported earlier, has prompted the synthesis of four new ergoline analogs that can be labeled with I-123. The radioactive iodoergoline derivatives Ia and II were synthesized in a radiochemical yield of 80% and 30% respectively, by refluxing the corresponding 8β-mesyl derivatives with [I-125]-NaI in absolute ethanol. Their chromatographic purification yielded no-carrier added compounds. Ib and Ic were synthesized in a radiochemical yield of 75% and 40% respectively, by refluxing the 8β-(o-iodobenzoyl)- and the 8β-(p-iodobenzenesulfonyl)-lysergol derivatives with [I-125]-NaI. Chromatographic purification yielded compounds with specific activities of --0.3 mCi/mg. Biodistribution studies performed in mature male rats after injection of 2-7 μCi of the compounds, showed high uptake of Ia, Ib and II in the brain and adrenals up to 30 min. This data is in agreement with previously studied Se-75 labeled closely related derivatives. Compound II showed, at maximum uptake time, the highest target/non-target ratios. Complete chemical, radiochemical synthesis, and structure biodistribution relationships are presented to support the hypothesis that radiolabeled ergolines could potentially be used as dopamine receptor site mapping agents