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

Nucl Med Biol. 1999 Aug;26(6):711-6. doi: 10.1016/s0969-8051(99)00028-1.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cysteine
  • Histidine
  • Humans
  • Indicators and Reagents
  • Metabolic Clearance Rate
  • Mice
  • Molecular Structure
  • Organotechnetium Compounds / chemical synthesis*
  • Organotechnetium Compounds / pharmacokinetics*
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics*
  • Serum Albumin
  • Technetium / pharmacokinetics
  • Tissue Distribution

Substances

  • Indicators and Reagents
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • Serum Albumin
  • Histidine
  • Technetium
  • Cysteine