Synthesis, chemical, radiochemical and radiobiological evaluation of a new 99mTc-labelled bombesin-like peptide.
A new pentadecapeptide bombesin analogue was prepared by Fmoc synthesis, purified by HPLC and identified by electron ionization mass spectrometry. The biological activity of the new peptide was tested on isolated human colonic muscle cells and compared to native bombesin. Labelling of the new biomolecule with Tc-99m yielded a single radioactive species which remained stable at room temperature for eight hours. In a binding assay, the radiolabelled peptide showed high affinity for oat-cell carcinoma (Kd = 9.8 nM) and colorectal adenocarcinoma (Kd = 27.2 nM). Biodistribution studies, performed in normal rodents, indicated uptake by organs that normally express bombesin receptors, such as liver, intestines and kidneys. Scintigraphic studies, performed in nude mice transplanted with small cell lung carcinoma and colon cancer cells, showed significant tumor uptake two hours p.i. The new synthetic pentadecapeptide appears to have promise for several malignancies, including oat-cell lung carcinoma, colorectal cancer and gastroenteropancreatic (GEP) tumors.
National Center for Scientific Research Demokritos, Athens 153 10, Hellas, Greece. avar@mail.demokritos.gr
A D
AD
Varvarigou
F
F
Scopinaro
L
L
Leondiadis
V
V
Corleto
O
O
Schillaci
G
G
De Vincentis
T G
TG
Sourlingas
K E
KE
Sekeri-Pataryas
G P
GP
Evangelatos
A
A
Leonti
S
S
Xanthopoulos
G
G
Delle Fave
S C
SC
Archimandritis
D000818:Animals; D001839:Bombesin / Q000138:chemical synthesis / Q000493:pharmacokinetics; D018288:Carcinoma, Small Cell / Q000000981:diagnostic imaging* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D006801:Humans; D007553:Isotope Labeling; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010455:Peptides / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D018004:Receptors, Bombesin / Q000378:metabolism; D013670:Sodium Pertechnetate Tc 99m; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D010455:Peptides; D018004:Receptors, Bombesin; D013670:Sodium Pertechnetate Tc 99m; D001839:Bombesin