CANCER BIOTHERAPY & RADIOPHARMACEUTICALS Volume 17, Number 3, 2002 © Mary Ann Liebert, Inc. Synthesis, Chemical, Radiochemical and Radiobiological Evaluation of a New 99m Tc-labelled Bombesin-like Peptide A.D. Varvarigou, 1 F. Scopinaro, 2 L. Leondiadis, 1 V. Corleto, 2 O. Schillaci, 2 G. De Vincentis, 2 T.G. Sourlingas, 1 K.E. Sekeri-Pataryas, 1 G.P. Evangelatos, 1 A. Leonti, 3 S. Xanthopoulos, 1 G. Delle Fave 2 and S.C. Archimandritis 1 1 National Center for Scientific Research “Demokritos”, Athens 153 10, Hellas; 2 Universitá “La Sapienza”, Rome, Italy; 3 “Alexandra” University Hospital, Athens, Hellas A new pentadecapeptide bombesin analogue was prepared by Fmoc synthesis, purified by HPLC and iden- tified 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 (K d 5 9.8 nM) and colorectal adenocarcinoma (K d 5 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 pentadecapep- tide appears to have promise for several malignancies, including oat-cell lung carcinoma, colorectal can- cer and gastroenteropancreatic (GEP) tumors. 317 INTRODUCTION Small neuropeptides, labelled with gamma and/or beta emitting radionuclides, are currently being investigated for their ability to bind to cell-sur- face receptors, which are overexpressed in some malignant tissues. 1 These molecules are poten- tially useful for radionuclide detection and/or therapy of tumors. At the moment neuroen- docrine tumors represent the most intriguing cat- egory of target tissues for radiolabelled peptides. 2 111 In octreotide, a somatostatin analogue, has generated increasing interest for the diagnosis and localization of a number of endocrine tumors including tumors of the hypophysis, thyroid, adrenals, small cell lung carcinomas and neu- roendocrine gastroenteropancreatic (GEP) tu- mors. 3–8 Several non endocrine carcinomas, such as lung adenocarcinoma 9 and breast cancer 10 have also shown enhanced uptake of 111 In-oc- treotide. Attention has also been focused on the amphibian peptide bombesin (BN), originally isolated from frog skin 7 and the molecularly re- lated-gastrin releasing peptide (GRP). Overex- pression of receptors for both BN and GRP has been encountered on the cell surface of several malignant tissues, particularly in the case of lung cancer 11–13 and colon cancer. 14,15 These peptides act as neurotransmitters and endocrine cancer cell growth factors. 16,17 In recent investigations mod- ification of their structure has been attempted in order to obtain derivatives which might easily be labeled with radionuclides, suitable for use in imaging and therapy. Thus, 125 I-Tyr 4 -BN is al- Address reprint requests to Alexandra Varvarigou, Na- tional Center for Scientific Research “Demokritos”, 153 10 Agia Paraskevi Attikis, Greece E-mail: avar @mail.demokritos.gr.