The synthesis and characterization of metal complexes for imaging and therapy

Tumor cell receptors, such as sigma receptors are expressed during the different stages of abnormal tissue behavior, and are thus, targets for radiopharmaceutical chemistry. Our approach has been to pursue the synthesis of derivatives of N1, N2-bis(3,4-dichlorophenethyl) ethane-1,2-diamine, and the determination of their affinity to the sigma 1 receptor. The 3 and 4 halogenated derivatives had affinities less than 20 nM, but possessed a lipophilicity value between 2-4. The derivatives N-[2-(3,4-Dichlorophenyl)-ethyl]-N'-[2-(4-fluorophenyl)-ethyl]-ethane-1,2-diamine and N-[2-(3,4-Dichlorophenyl)-ethyl]-N'-[2-(3-fluorophenyl)-ethyl]-ethane-1,2-diamine gave greater binding affinities to the sigma 1 receptor. Derivatives containing tertiary amines had similar binding affinities to the receptor as secondary amines derivatives.; The development of metal based radiopharmaceuticals have been studied for their in vitro and in vivo stability, and compared to reported literature compounds. Stability of rhenium tricarbonyl complexes derived from bidentate or tridentate ligands were determined, and it was found that bidentate ligands with nitrogen donors will undergo exchange of chlorine. Complexes with tridentate ligands containing a pyridine and thiol were found to be unstable, however tridentate ligands with two pyridine ligands produced very stable complexes. The lipophilicity of the rhenium tricarbonyl derivatives were much higher than similar [99mTcO(N2S2)] complexes. Monoclonal antibody (B72.3) conjugates were prepared from the following DOTA derivatives 2-(p-SCN-benzyl) DOTA (antibody conjugated with a thiourea linked through the amine ring), N-(2'-{lcub}2'-methoxy, 4'-isothiocyanatophenyl{rcub}) DOTA (antibody conjugated with a thiourea group linked through the carbon on the acid arm), and DOTA-NHS (antibody conjugated with an amide group linked through the acid). The in vivo stability of antibody conjugates designed to chelate lanthanides were evaluated, where the lead compound had similar stability and biodistribution as the literature compounds.