New 18F-labelled neurotensin(8-13) analogs for positron emission tomography (PET): Pharamcological and biochemical charakterisation


New 18F-labelled neurotensin(8-13) analogs for positron emission tomography (PET): Pharamcological and biochemical charakterisation

Bergmann, R.; Scheunemann, M.; Mäding, P.; Rodig, H.; Kretzschmar, M.; Chavatte, K.; Tourwé, D.; Zips, D.; Brust, P.; Johannsen, B.

The potential of radiolabelled neurotensin ana-logues for in vivo imaging of neurotensin (NT) receptor overexpressing tumours by PET was studied.
Methods: Three newly synthesised 18F-radiolabelled NT(8-13) agonists, characterised by HPLC, mass spectrometry, and NMR were used for in vitro binding and internalisation stud-ies with HT-29 or WiDr cells. Ca2+ mobilisation was investigated using FLIPR measurements. Biodistribution studies were performed in nude mice bearing HT-29 or WiDr tumours without and with blocking of the NT receptors. Biokinetic studies were done in Wistar rats using PET. The specificity of the peptide binding to the tu-mour cells was studied in receptor blocking ex-periments.
Results: The KD's of the NT analogues were in the nanomolar range. The Ca2+ mobilisation ef-fect of the compounds were between 99% and 129% compared to NT with EC50 between 17nM and 120nM. The tumour uptake of the peptides was moderate and was highest for the double stabi-lised peptide {4-[18F]fluoro-benzoyl-Arg-Psi-(CH2-NH)-Arg-Pro-Phe11-T-Leu12-Leu-OH (FB-P3)} (3.5% ID/g tissue 10 min p.i.). It was specifically accumulated in vitro and also in vivo in the tumours (70% inhibition by NT(8-13)). In nude mice the tumour was clearly visible with PET if the location was distant from the excre-tory organs.
Conclusion: The 18F-labeled stabilised NT analogues are NT agonists and potential radiotrac-ers for imaging of neurotensin receptor ex-pressing tumours. However, structural optimisa-tion is still needed.
(supported by the EC, Contract No. BMH4-CT98-3198)

  • Lecture (Conference)
    International Conference on Peptide Radiopharmaceuticals in Diagnosis and Therapy, Rome, 25.-28.05.2000
  • Abstract in refereed journal
    Nuclear Medicine Communications 21 No. 6 (2000) 565-566

Permalink: https://www.hzdr.de/publications/Publ-3260
Publ.-Id: 3260