Catabolism of neurotensins. Implications for the design of radiolabeling strategies of peptides.
A major impact in diagnosis and treatment of cancer with peptide based radiopharmaceuticals is expected. Among others neurotensin is considered to be a promising candidate. However, most neurotensin analogues, which bind to the neurotensin receptor have a too short biological half live due to catabolism. Therefore, stabilized fragments have been prepared and labeled with the newly developed [Tc(CO)3](+)-moiety. A single histidine or a (N alpha-His)-Ac group coupled to the N-terminus of the neurotensin fragments were used as a bidentate or a tridentate ligand respectively, which coordinate the metal carbonyl efficiently. Affinity and binding studies of the 99mTc(I) radiolabeled neurotensin fragments revealed a behavior influenced by catabolism and properties of the metal complex.
Schubiger
P A
PA
Center for Radiopharmaceutical Science, Swiss Federal Institute of Technology, Zurich.
Allemann-Tannahill
L
L
Egli
A
A
Schibli
R
R
Alberto
R
R
Carrel-Rémy
N
N
Willmann
M
M
Bläuenstein
P
P
Tourwé
D
D
D000345:Affinity Labels; D001665:Binding Sites; D006207:Half-Life; D006639:Histidine / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy; D009496:Neurotensin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000737:chemistry; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D018028:Receptors, Neurotensin / Q000378:metabolism
D000345:Affinity Labels; D008024:Ligands; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D018028:Receptors, Neurotensin; D009496:Neurotensin; D006639:Histidine