Rhenium (Re) and technetium (Tc)-99M oxocomplexes of neurotensin(8-13)

Abstract

Radio-labelled Neurotensin (NT) analogues have applications as potential tumour imaging agents. In this study, the N2N′S chelator dimethylGly-Ser-Cys (acetomidomethyl)-Gly (RP414) was attached to the N-terminus of four different NT(8-13) analogues. DimethylGly-Ser-Cys(acetoamidomethyl)-Gly (RP414) co-ordinates strongly to MO3+ (M=Tc or Re) making this chelator ideal for labelling NT with either Tc-99m or Re. One step labelling at room temperature with Tc-99m was performed using stannous gluconate at pH 5. Labelling yields >98% were obtained within 1 hour. Re (V) oxo complexes were synthesised in a two-steps synthesis including deprotection of the chelator using mercuric acetate followed by complexation with Re using bisethylenediamino dioxorhenium (V)chloride (ReO2(en)2Cl). All Re(V)oxo-NT analogues showed in vitro half-lives in plasma of between 20 and 30 minutes. Inhibition of the binding of 3H-NT on HT29 colon adeno carcinoma cells yielded Ki values of 1.0 nM for NT(1–13) and 0.8 nM, 5.5 nM and 4.0 nM for the Re(V) oxo complexes of RP414-Arg-Arg-NT(10–13), RP414-Lys-Arg-NT(10–13) and RP414-Lys-Lys-NT(10–13) respectively. Copyright © 1999 John Wiley & Sons, Ltd.