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Metabolism and localization properties of 99m Tc labeled synthetic neurotensin analogs
Author(s) -
Nock B.,
Maina T.,
Nikolopoulou A.,
Tsipra C.,
Poppe M.,
Conrath P.,
Tourwé D.,
Chiotellis E.
Publication year - 2001
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.25804401205
Subject(s) - neurotensin , chemistry , internalization , in vivo , neurotensin receptor , kidney , biochemistry , receptor , peptide , neuropeptide , medicine , microbiology and biotechnology , biology
Abstract Recent reports have demonstrated that neurotensin (NT) receptors are overexpressed at high density in such devastating human neoplasms like exocrine ductal pancreatic carcinomas. Consequently, radiolabeled NT analogs can be used in the early diagnosis or even treatment of such tumors. In the present study we report on the synthesis and preclinical evaluation of four 99m Tc labeled synthetic NT analogs based on the NT(8–13) sequence, known to specifically interact with the NTR1 subtype found in neoplastic cells. The biological half life of these analogs has been increased by strategic reduction of amide bonds, replacement of amino acid residues and coupling of a tetramine bifunctional chelator at the N‐terminal of resulting peptides. The affinity for the NTR1 subtype was found high in competition binding assays in WiDr cell membrane preparations. Labeling with 99m Tc was quantitative under mild conditions leading to single radioactive species in high specific activities. The stability of labeled peptides in plasma, urine and kidney homogenates was found dependent on the above described modifications. The rate of internalization in WiDr cells was very high for all radiolabeled peptides, with >90% of the radioactivity accumulating in the cells within 30 min. In vivo distribution of the two most stable 99m Tc NT analogs in mice xenografts revealed a specific accumulation of radioactivity in NTR1 subtype — rich cancer tissue combined with a very rapid clearance of background activity through the kidneys and the urinary system.