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A Journal on Nuclear Medicine and Molecular Imaging
Affiliated to the and to the International Research Group of Immunoscintigraphy
Indexed/Abstracted in: Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index (SciSearch), Scopus
Impact Factor 2,413
Online ISSN 1827-1936
MOLECULAR MANIPULATION AND PHARMACOKINETICS
Hansen L., Marzilli L. G.*, Taylor A.
From the Department of Radiology *Department of Chemistry Emory University School of Medicine, Atlanta, GA, USA
The influence of stereoisomerism on the pharmacokinetics of Tc mono-oxo complexes is reviewed. Tc(V) mono-oxo complexes formed with N/S ligands have four donor groups from the ligands in an equatorial plane; the oxo ligand coordinates in an axial position. Stereoisomerism in Tc (V) mono-oxo complexes can be centered within the ligand (carbon atom in the chelate ring or ligating nitrogen of amine donors) or at the Tc. The metal center becomes chiral when an equatorial ligand has a head and a tail (i.e., the two ends of the ligand differ). All types of stereocenters can produce significantly different pharmacokinetic profiles for individual isomers. Thus, biological evaluation of separated stereoisomers is necessary to identify the optimal stereochemical configuration, particularly for radiopharmaceuticals targeted to receptor molecules with low specificity. Because of interspecies variation, there is ultimately no substitute for human testing. Although it is possible that the increase in nonspecific binding of agents incorporating L- vs D-amino acids may more than offset any increased receptor binding, much more information is needed. Stereochemical factors can also lead to unpredictable differences in coordination geometry and thermodynamic preference of a single isomer; thus chemical characterization of stereoisomers continues to be an important component of radiopharmaceutical development.