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    Design and synthesis of Tc-99m-citro-folate for use as a tumor-targeted radiopharmaceutical
    (Elsevier Science Bv, 2010) Altiparmak, Burcu; Lambrecht, Fatma Yurt; Bayrak, Elif; Durkan, Kubra
    Folate conjugates exhibit high affinity for folate receptor (FR) positive cells and tissues, such as those in tumors, making them attractive candidates and of interest in diagnostic tumor imaging. The aim of study was to synthesize a novel radiopharmaceutical based folate conjugate, Tc-99m-citro-folate, and to evaluate its efficiency as a targeted agent for imaging tumors that over express FR. TLC, HPLC H-1 NMR and LC-MS/MS methods were used to check and confirm the synthesized citro-folate. Citro-folate was labeled with Tc-99m with high labeling efficiency (97 +/- 1.0%). Biodistribution of the radiolabeled conjugate Tc-99m-citro-folate was investigated in vivo using two groups of rats: FR saturated and unsaturated. These experiments showed high uptake of Tc-99m-citro-folate in FR rich tissues and demonstrated its sensitivity and specificity in imaging ovary and uterus. Based on the demonstrated good radiolabeling and biodistribution properties, the compound Tc-99m-citro-folate may potentially be used as a radiopharmaceutical agent for imaging the FR-positive tumors. (C) 2010 Elsevier B.V. All rights reserved.
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    Design of radiolabeled gelatinase inhibitor peptide (Tc-99m-CLP) and evaluation in rats
    (Pergamon-Elsevier Science Ltd, 2014) Altiparmak, Burcu; Lambrecht, Fatma Yurt; Citak, Asli
    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 Tc-99m 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, Tc-99m-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 Tc-99m 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. (C) 2014 Elsevier Ltd. All rights reserved.
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    Design of Radiolabeled Gelatinase Inhibitor Peptide with for Imaging of Gelatinase Activity in Tumors
    (Springer, 2012) Altiparmak, B.; Altiparmak, Burcu; Lambrecht, Fatma Yurt
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    Design of Tc-99m-DTPA-CLP and Preliminary Evaluation in Rats
    (Wiley-Blackwell, 2014) Altiparmak, Burcu; Lambrecht, Fatma Y.; Er, Ozge
    Radiopharmaceuticals are localized in (malignant) tumor tissues by different mechanisms. One of these mechanisms, gelatinase enzyme activity, is associated with poor prognosis in cancer patients and potential targets for tumor imaging. There are some gelatinases to be associated with metastatic potential for tumor imaging to possibly predict metastases. In this study, a cyclic decapeptide conjugate, DTPA-CLP (DTPA-Cys-Leu-Pro-Gly-His-Trp-Gly-Phe-Pro-Ser-Cys), was selected as a peptide conjugate because of its selective inhibitory activity toward gelatinases. Peptide-conjugated DTPA-CLP was labeled with Tc-99m with a radiolabeling efficiency of 97.0 +/- 2.8%. After determining optimization conditions for radiolabeling, a biodistribution study of radiolabeled peptide in albino Wistar rats was performed. According to biodistribution data, Tc-99m-DTPA-CLP showed high uptake in the lung, liver, uterus, and spleen. These results show that Tc-99m-DTPA-CLP may be used for the imaging of gelatinase activity in metastatic tumors.