99m-Technetium-labelled peptide-HYNIC conjugates: effects of lipophilicity and stability on biodistribution

• Published in: Nuclear medicine and biology Vol. 26; no. 4; pp. 389 - 396
• Main Authors: Decristoforo, Clemens, Mather, Stephen J
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.05.1999; Elsevier
• Subjects: Animals; Biological and medical sciences; Chromatography, High Pressure Liquid; Co-ligands; Contrast media. Radiopharmaceuticals; Drug Stability; Hydrazines - chemistry; HYNIC; Isotope Labeling; Male; Medical sciences; Nicotinic Acids - chemistry; Peptides; Peptides - pharmacokinetics; Pharmacokinetics; Pharmacology. Drug treatments; Protein Binding; Rats; Rats, Wistar; Solubility; Technetium; Tissue Distribution; Peptides; Technetium; TFA; SB; HYNIC; EtEDTA; DMF; NSB; 3-PSA; PBS; Co-ligands; Bz 2EDDA; ACN; EDTA; Me 2EDDA; PAA; MEK; BzEDTA; NA; 4-PSA; PDCA; Pharmacokinetics; EDDA; Et 2EDDA; INA; BFC; Parameter estimation; Stability; Radiolabelling; Rat; Ligand; Rodentia; Lipophily; In vitro; In vivo; Vertebrata; Mammalia; Animal; Distribution
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/S0969-8051(98)00118-8

The aim of this study was to explore the effects of lipophilicity and stability on the biodistribution of 99mTc labelled peptides through the use of different co-ligands. 6-Hydrazinopyridine-3-carboxylic acid (HYNIC) was coupled to the somatostatin analogue RC160 and radiolabelled using a range of ethylendiaminediacetic acid (EDDA) and ethylenediaminetetraacetic acid (EDTA) derivatives as well as tricine and pyridine/tricine as co-ligands. After labelling with technetium-99m, chromatographic, stability, protein-binding, and rat biodistribution studies were performed. For most co-ligands, biodistribution correlated well with in vitro properties. Lipophilic substitution on EDDA resulted in higher protein binding, increased liver uptake, and intestinal excretion. Stabilisation of tricine with pyridines reduced blood levels and lowered liver uptake. EDTA derivatives showed high instability in vitro and in vivo.