Labelling and evaluation of new stabilised neurotensin (8-13) analogues for single photon emission tomography (SPET)

Abstract

Neurotensin(8–13) analogues were biologically stabilised by replacement of the peptide bond between amino acids 8 and 9 by the reduced ψ(CH2-NH) isostere. Diethylenetriaminepentaacetic acid (DTPA) analogues for In-111 labelling and 2-bromo-phenyl-acetyl analogues for radioiodination, showed receptor affinities in the nanomolar range in combination with a biological half life in human plasma up to 275 minutes. Biodistribution studies in male Wistar rats of metabolically stabilised and non-stabilised 111In-DTPA-NT(8–13) analogues showed a major clearance from the blood through the kidneys. 125I-Labelled neurotensin (8–13) analogues showed accumulation up to 2.2% of the injected dose per g tissue in the liver which might be an important disadvantage when diagnosis of tumours in the gut is aimed. Neurotensin(8–13) analogues labelled with In-111 or I-123 may act as new potential peptidergic radiopharmaceuticals for SPET diagnosis of neurotensin receptor (NTR) positive tumours. Copyright © 1999 John Wiley & Sons, Ltd.