In vitro and in vivo evaluation of bidentate, water-soluble phosphine ligands as anchor groups for the organometallic fac-[99mTc(CO)3]+-core

The organometallic precursor fac-[Tc-99m(OH2)(3)(CO)(3)](+), 1a, was reacted with the bidentate, water-soluble phosphine ligands bis(bis(hydroxymethyl)phosphino)ethane (HMPE) and bis(bis(hydroxymethyl)phosphino)benzene (HMPB) in 0.9% saline to produce complexes in >95% yields. High performance liquid chromatography analyses indicate the initial formation of the complexes fac-[(TcCl)-Tc-99m(CO)(3)L] (L = HMPE 2a, HMPB 3a). The neutral complexes ultimately lose the coordinated chloride to produce the cationic species fac-[Tc-99m(OH2)(CO)(3)L](+) 2b/3b. In vitro studies showed a high stability of 2b/3b over a wide pH range for > 24 h. No decomposition or alteration of the complexes was observed even in the presence of excess histidine, cysteine, or human serum albumin. Experiments performed in normal mice demonstrated a fast clearance of the cationic compounds 2b/3b from the brood pool and clearance through the hepatobiliary and the urinary pathways. NUCL MED BIOL 26;6:711-716, 1999. (C) 1999 Elsevier Science Inc. All rights reserved.