99m-technetium-labelled peptide-HYNIC conjugates: Effects of lipophilicityand stability on biodistribution

The aim of this study was to explore the effects of lipophilicity and stabi lity on the biodistribution of (99mT)c labelled peptides through the use of different co-ligands. 6-Hydrazinopyridine-3-carboxylic acid (HYNIC) was co upled to the somatostatin analogue RC160 and radiolabelled using a range of ethylendiaminediacetic acid (EDDA) and ethylenediaminetetraacetic acid (ED TA) derivatives as well as tricine and pyridine/tricine as co-ligands. Afte r labelling with technetium-99m, chromatographic, stability, protein-bindin g, and rat biodistribution studies were performed. For most co-ligands, bio distribution correlated well with in vitro properties. Lipophilic substitut ion on EDDA resulted in higher protein binding, increased liver uptake, and intestinal excretion. Stabilisation of tricine with pyridines reduced bloo d levels and lowered liver uptake. EDTA derivatives showed high instability in vitro and in vivo. NUCL MED BIOL 26;4: 389-396, 1999. (C) 1999 Elsevier Science Inc. All rights reserved.