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

Abstract

The organometallic precursor fac-[ 99mTc(OH 2) 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-[ 99mTcCl(CO) 3L] ( L= HMPE 2 a, HMPB 3 a). The neutral complexes ultimately lose the coordinated chloride to produce the cationic species fac-[ 99mTc(OH 2)(CO) 3L] + 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 blood pool and clearance through the hepatobiliary and the urinary pathways.