title: Comparative assessment of a99mTc labeled H1299.2-HYNIC peptide bearing two different co-ligands for tumor-targeted imaging.
abstract: Peptides are a class of targeting agents that bind to cancer-specific cell surfaces. Since they specifically target cancer cells, they could be used as molecular imaging tools. In this study, the 15-mer peptide Ac-H1299.2 (YAAWPASGAWTGTAP) was conjugated with HYNIC via lysine amino acid on C-terminus and labeled with99mTc using tricine and EDDA/tricine as the co-ligands. These radiotracers were evaluated for potential utilization in diagnostic imaging of ovarian cancer cells (SKOV-3). The cell-specificity of these radiolabeled peptides was determined based on their binding on an ovarian cancer cell line (SKOV-3), and displaying a low affinity for lung adenocarcinoma cell line (A549) and breast cancer cell line (MCF7). Biodistribution studies were conducted in normal mice as well as in nude mice bearing SKOV-3 ovarian cancer xenografts. HYNIC-peptide was labeled with99mTc with more than 99% efficiency and showed high stability in buffer and serum. We observed nanomolar binding affinities for both radiolabeled peptides. The tumor uptakes were 3.27%±0.46% and 1.55%±0.20% for tricine and 2.34±1.1% and 1.09%±0.18% for EDDA/tricine at 1 and 4h after injection, respectively. A higher tumor to background ratio and lower radioactivity in the blood were observed for EDDA/tricine co-ligands, leading to clear tumor visualization in imaging with injection of this peptide. This new99mTc-labeled peptide selectively targeted ovarian cancer and introduction of a (EDDA/tricine) as a co-ligand improved the pharmacokinetics of99mTc-labeled H1299.2 for tumor imaging in animals.
authors.affiliation: Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Seyedeh Atekeh
authors.initials: SA
authors.lastname: Torabizadeh
authors.affiliation: Department of Radiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Cardiovascular Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Abedi
authors.affiliation: Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Noaparast
authors.affiliation: Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address: sjhosseinim@yahoo.com.
authors.forename: Seyed Jalal
authors.initials: SJ
authors.lastname: Hosseinimehr
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis / Q000494:pharmacology; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000494:pharmacology*; D004355:Drug Stability; D004492:Edetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008819:Mice, Nude; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D002614:Chelating Agents; D056831:Coordination Complexes; D008024:Ligands; D015609:Organotechnetium Compounds; D010455:Peptides; D019275:Radiopharmaceuticals; C000625354:technetium 99m H1299.2-HYNIC; C026058:EDDA; D004492:Edetic Acid; D005998:Glycine; C100184:tricine
keywords: (99m)Tc; EDDA; H1299.2 peptide; Ovarian cancer; Tricine; Tumor imaging