Τίτλος:
Structural assessment and biological evaluation of two N3S bombesin derivatives
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The aim of the present study is the evaluation of the 99mTc complexes of two bombesin-like peptides: Gly1′-Gly2′-Cys3′- Aca-BN[2-14] (BN-1.1) and Gly1′-Gly2′-Cys3′-Aca-BN[7-14] (BN-1.1p). The BN derivatives were synthesized according to the solid phase peptide synthesis method, and characterized by ESI-MS and NMR. 185/187Re-BN-1.1 and 185/187Re-BN-1.1p were also identified by ESI-MS and NMR. The 99mTc complexes were stable over time in human plasma, while they degraded rapidly in kidney-liver homogenates. The peptides and their 99mTc complexes showed high affinity for the human GRP receptors expressed in PC-3 cells. The rate of internalization of these radiolabeled biomolecules was found to be time-dependent. Also, it was found that there was no long-term retention of the radioactive metabolites into the cells. Tissue distribution of the radiopeptides was evaluated in normal mice and in prostate cancer experimental models. Significant uptake of radioactivity was observed in the pancreas of PC-3 tumor-bearing SCID mice. Dynamic studies of both radiopeptides showed satisfactory tumor images. © 2009 American Chemical Society.
Συγγραφείς:
Gourni, E.
Bouziotis, P.
Benaki, D.
Loudos, G.
Xanthopoulos, S.
Paravatou-Petsotas, M.
Mavri-Vavagianni, M.
Pelecanou, M.
Archimandritis, S.C.
Varvarigou, A.D.
Περιοδικό:
Journal of Medicinal Chemistry
Λέξεις-κλειδιά:
bombesin 1.1 re 185; bombesin 1.1 re 187; bombesin 1.1 tc 99m; bombesin 1.1p re 185; bombesin 1.1p re 187; bombesin 1.1p tc 99m; bombesin derivative; drug metabolite; gastrin releasing peptide receptor; technetium 99m; unclassified drug, animal experiment; animal model; article; binding competition; cancer model; carbon nuclear magnetic resonance; drug accumulation; drug clearance; drug degradation; drug metabolism; drug receptor binding; drug screening; drug selectivity; drug synthesis; drug uptake; electrospray mass spectrometry; human; human cell; internalization; isotope labeling; kidney homogenate; liver homogenate; male; molecular stability; mouse; nonhuman; prostate cancer; proton nuclear magnetic resonance; radioactivity; receptor affinity; SCID mouse; single photon emission computer tomography; solid phase synthesis; structure activity relation; time; tissue distribution, Animals; Binding, Competitive; Bombesin; Cell Line, Tumor; Female; Humans; Magnetic Resonance Spectroscopy; Male; Mice; Oligopeptides; Organotechnetium Compounds; Protein Stability; Protein Transport; Spectrometry, Mass, Electrospray Ionization; Staining and Labeling; Tissue Distribution
