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

Radio-labelled Neurotensin (NT) analogues have applications as potential tu mour imaging agents. In this study, the N2N'S chelator dimethylGly-Ser-Cys (acetoamidomethyl)-Gly (RP414) was attached to the N-terminus of four diffe rent NT(8-13) analogues. DimethylGly-Ser-Cys(acetoamidomethyl)-Gly(RP414) c oordinates strongly to MO3+ (M = Te or Re) making this chelator ideal for l abelling NT with either Tc-99m or Re. One step labelling at room temperatur e with Tc-99m was performed using stannous gluconate at pH 5. Labelling yie lds > 98% were obtained within 1 hour. Re (V) oxo complexes were synthesise d in a two-steps synthesis including deprotection of the chelator using mer curic acetate followed by complexation with Re using bisethylenediamino dio xorhenium (V)chloride (ReO2(en)(2)Cl). All Re(V)oxo-NT analogues showed in vitro half-lives in plasma of between 20 and 30 minutes. Inhibition of the binding of H-3-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 complexe s of RP414-Arg-Arg-NT(10-13), RP414-Lys-Arg-NT(10-13) and RP414-Lvs-Lys-NT( 10-13) respectively.