title: Synthesis, characterization, conformational analysis of a cyclic conjugated octreotate peptide and biological evaluation of (99m)Tc-HYNIC-His(3)-Octreotate as novel tracer for the imaging of somatostatin receptor-positive tumors.
abstract: Peptides are attracting increasing interest in nuclear oncology for targeted tumor diagnosis and therapy. We therefore synthesized new cyclic octapeptides conjugated with HYNIC by Fmoc solid-phase peptide synthesis. These were purified and analyzed by RP-HPLC, MALDI mass, (1)H NMR, (13)C NMR, HSQC, HMBC, COSY and IR spectroscopy. Conformational analysis of the peptides was performed by circular dichroism spectroscopy, in pure water and trifluoroethanol-water (1:1), revealed the presence of strong secondary structural features like β-sheet and random coils. Labeling was performed with (99m)Tc using Tricine and EDDA as coligands by SnCl(2) method to get products with excellent radiochemical purity >99.5 %. Metabolic stability analysis did not show any evidence of breaking of the labeled compounds and formation of free (99m)Tc. Internalization studies were done and IC(50) values were determined in somatostatin receptor-expressing C6 glioma cell line and rat brain cortex membrane, and the results compared with HYNIC-TOC as standard. The IC(50) values of (99m)Tc-HYNIC-His(3)-Octreotate (21 ± 0.93 nM) and (99m)Tc-HYNIC-TOC (2.87 ± 0.41 nM) proved to be comparable. Biodistribution and image study on normal rat under gamma camera showed very high uptake in kidney and urine, indicating kidney as primary organ for metabolism and route of excretion. Biodistribution and image study on rats bearing C6 glioma tumor found high uptake in tumor (1.27 ± 0.15) and pancreas (1.71 ± 0.03). Using these findings, new derivatives can be prepared to develop (99m)Tc radiopharmaceuticals for imaging somatostatin receptor-positive tumors.
authors.affiliation: Department of Nuclear Medicine, Infectious Disease and Immunology Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata 700032, India. ashubehu2000@gmail.com
authors.forename: Ashok
authors.initials: A
authors.lastname: Behera
authors.forename: Indranil
authors.initials: I
authors.lastname: Banerjee
authors.forename: Kakali
authors.initials: K
authors.lastname: De
authors.forename: Rudra Narayan
authors.initials: RN
authors.lastname: Munda
authors.forename: Sankha
authors.initials: S
authors.lastname: Chattopadhayay
authors.forename: Amalesh
authors.initials: A
authors.lastname: Samanta
authors.forename: Bharat
authors.initials: B
authors.lastname: Sarkar
authors.forename: Santanu
authors.initials: S
authors.lastname: Ganguly
authors.forename: Mridula
authors.initials: M
authors.lastname: Misra
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D057054:Molecular Imaging; D009369:Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000378:metabolism*; D060327:Solid-Phase Synthesis Techniques; D014018:Tissue Distribution
chemical_list: D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin