Structural assessment and biological evaluation of two N3S bombesin derivatives.
The aim of the present study is the evaluation of the (99m)Tc 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. (185/187)Re-BN-1.1 and (185/187)Re-BN-1.1p were also identified by ESI-MS and NMR. The (99m)Tc complexes were stable over time in human plasma, while they degraded rapidly in kidney-liver homogenates. The peptides and their (99m)Tc 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.
Gourni
Eleni
E
Institutes of Radioisotopes-Radiodiagnostic Products and Biology, NCSR Demokritos, 15310 Athens, Greece.
Bouziotis
Penelope
P
Benaki
Dimitra
D
Loudos
George
G
Xanthopoulos
Stavros
S
Paravatou-Petsotas
Maria
M
Mavri-Vavagianni
Maria
M
Pelecanou
Maria
M
Archimandritis
Spyros C
SC
Varvarigou
Alexandra D
AD
D000818:Animals; D001667:Binding, Competitive; D001839:Bombesin / Q000737:chemistry*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000737:chemistry; D055550:Protein Stability; D021381:Protein Transport; D021241:Spectrometry, Mass, Electrospray Ionization; D013194:Staining and Labeling; D014018:Tissue Distribution
D009842:Oligopeptides; D015609:Organotechnetium Compounds; D001839:Bombesin