title: Design of radiolabeled gelatinase inhibitor peptide ((99m)Tc-CLP) and evaluation in rats.
abstract: In malignant tissues, MMP-9 (gelatinase B, 92 kDa type IV collagenase) and MMP-2 (gelatinase A, 72 kDa type IV collagenase) are the most prevalent matrix metalloproteinases related to the tumor aggressiveness and metastatic potential. Since elevated levels of gelatinases are associated with poor prognosis in cancer patients, these enzymes are potential targets for tumor imaging to possibly predict metastases. In the present study, a cyclic decapeptide, CLP (Cys-Leu-Pro-Gly-His-Trp-Gly-Phe-Pro-Ser-Cys), was selected as a basic peptide because of its selective inhibitory activity toward gelatinases. The peptide was labelled with (99m)Tc with a radiolabelling efficiency of 94.6±4.1%. After determining the appropriate conditions for radiolabelling, a biodistribution study of radiolabelled peptide in Albino Wistar rats was done. According to biodistribution data, (99m)Tc-CLP showed high uptake in the lung, liver, uterus and spleen. The amount of normal tissue MMPs enzymes is known to be lower than a tumor tissue. In this connection, our findings show that matrix metalloproteinases inhibitory peptide which is CLP is labeled with (99m)Tc with high yield and radiolabeled peptide might be might be utilized for the imaging of gelatinase activity due to overexpression of MMP-2 and MMP-9 in tumor tissue.
authors.affiliation: Department of Nuclear Applications, Institute of Nuclear Science, Ege University, Bornova, 35100 Izmir, Turkey.
authors.forename: Burcu
authors.initials: B
authors.lastname: Altıparmak
authors.affiliation: Department of Nuclear Applications, Institute of Nuclear Science, Ege University, Bornova, 35100 Izmir, Turkey. Electronic address: fatma.yurt.lambrecht@ege.edu.tr.
authors.forename: Fatma Yurt
authors.initials: FY
authors.lastname: Lambrecht
authors.affiliation: Department of Nuclear Applications, Institute of Nuclear Science, Ege University, Bornova, 35100 Izmir, Turkey.
authors.forename: Asli
authors.initials: A
authors.lastname: Citak
mesh_terms: D000818:Animals; D005260:Female; D018093:Gelatinases / Q000037:antagonists & inhibitors; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012588:Scintillation Counting; D013667:Technetium / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D009842:Oligopeptides; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D013667:Technetium; D018093:Gelatinases
keywords: Gelatinase; HWGF-containing peptide; Matrix metalloproteinases; Radiolabeled peptide