Targeting radiopharmaceuticals: comparative biodistribution studies of gallium and indium complexes of multidentate...

New multidentate ligands with structures similar to N,N'-bis[2-hydroxybenzyl]ethylenediamine-N,N'-diacetic acid (HBED) and N,N'-bis(pyridoxyl)ethylenediamine-N,N'-diacetic acid (PLED) were synthesized. The in vitro lipophilicity, electrophoretic behavior, and the in vitro biodistribution were studied for the 111In- and 67, 68Ga-complexes of N,N'-bis(2-hydroxy-3,5-dimethylbenzyl)ethylenediamine-N,N'-diacetic acid (Me4HBED); N,N'-bis(5-t-butyl-2-hydroxy-3-methylbenzyl)ethylenediamine-N,N'-diac eti c acid (t-butyl HBED); N,N'-bis[2-hydroxy-5-sulfobenzyl)ethylenediamine-N,N'-diacetic acid (SHBED); N,N'-bis(2-hydroxy-3,5-dimethylbenzyl)ethylenediamine-N-(2-hydroxyethyl) -N'-acetic acid (HBMA); and N,N'-bis(5-deoxypyridoxyl)ethylenediamine-N,N'-diacetic acid (DPLED). The biodistribution of the radiometal complexes were carried out in rats and an imaging study was performed in a non-human primate. The rapid clearance of the lipophilic complexes from blood and through the hepatobiliary system was easily demonstrated; as well, the hydrophilic complexes were cleared rapidly through the urinary tract. Positron emission tomographic images were generated from a study in a primate after administration of 68Ga-t-butyl HBED. These images well demonstrate the efficient liver accumulation and rapid hepatobiliary clearance (less than 1 h) and well differentiate images of the liver and gall bladder.