title: 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(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-[99mTcCl(CO)3L] (L = HMPE 2a, HMPB 3a). The neutral complexes ultimately lose the coordinated chloride to produce the cationic species fac-[99mTc(OH2)(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.
authors.affiliation: Department of Radiology, University of Missouri-Columbia, USA.
authors.forename: R
authors.initials: R
authors.lastname: Schibli
authors.forename: K V
authors.initials: KV
authors.lastname: Katti
authors.forename: C
authors.initials: C
authors.lastname: Higginbotham
authors.forename: W A
authors.initials: WA
authors.lastname: Volkert
authors.forename: R
authors.initials: R
authors.lastname: Alberto
mesh_terms: D000818:Animals; D003545:Cysteine; D006639:Histidine; D006801:Humans; D007202:Indicators and Reagents; D008657:Metabolic Clearance Rate; D051379:Mice; D015394:Molecular Structure; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D012709:Serum Albumin; D013667:Technetium / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D007202:Indicators and Reagents; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D012709:Serum Albumin; D006639:Histidine; D013667:Technetium; D003545:Cysteine