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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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    Evaluation of Tc-99m-Pheophorbide-a use in infection imaging: A rat model
    (Pergamon-Elsevier Science Ltd, 2011) Ocakoglu, Kasim; Bayrak, Elif; Onursal, Mehmet; Yilmaz, Osman; Lambrecht, Fatma Yurt; Holzwarth, Alfred R.
    This study aims to prepare (99m)Technetium Pheophorbide-a (Tc-99m-PH-A) complex and evaluate its efficiency as an infection imaging agent. First, PH-A was obtained from Spirulina maxima algae, and the product compound was confirmed using H-1 NMR and MS (ESI) methods. The PH-A was then labeled with Tc-99m using the tin chloride method and its biological efficacy as a potential radiotracer for Staphylococcus aureus (S. aureus) infection was evaluated in bacterially infected and sterile inflamed rats. The radiochemical stability of the Tc-99m-PH-A in human serum was determined by thin-layer radiochromatography (TLRC). The radiochemical purity was 87 +/- 3.2% and remained constant at more than 80 +/- 0.1% even in serum for 120 min after radiolabeling. These experiments indicated that the ratio of Tc-99m-PH-A uptake in bacterially infected muscle, as compared to normal muscle, [target/non-target (T/NT)=5.6 at 1 h] was over four times higher than that in sterile inflamed muscle (T/NT=1.29 at 1 h). Disappearance of activity from the kidney and liver indicated that the urinary and hepatobiliary systems were the normal routes of excretion of the complex. (99m)Technetium Pheophorbide prepared with high yield is able to localize well in the bacterially infected muscle of the rats and Tc-99m-PH-A may be developed as a radiopharmaceutical agent to distinguish infection from inflammation by nuclear imaging. (C) 2011 Elsevier Ltd. All rights reserved.
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    Radiolabeling of EGCG with I-131 and biodistribution in rats
    (Birkhauser Boston Inc, 2012) Toksoz, Feriha; Demir, Ilknur; Bayrak, Elif; Kocagozoglu, Gamze; Onursal, Mehmet; Karademir, Gulgun; Lambrecht, Fatma Yurt
    Epigallocatechin gallate (EGCG), is the most abundant and widely studied catechin in green tea (Camellia sinensis Theaceae). The inhibitory effects of EGCG and green tea extract on carcinogenesis in various organs in rodents have now been demonstrated over the past decade. The aim of study was to label EGCG with I-131, to determinate its structure and to evaluate its biodistribution in Wistar rats. Radiolabeling was carried out by direct electrophilic iodination method (iodogen) and yield was determined by radio thin layer chromatography (RTLC). Radiolabelling yield is determined as 89 +/- A 1.0%. Besides, determination of structure of iodinated molecule, serum stability, and partition coefficient experiments was performed. The structure analysis of synthesized cold I-127-EGCG complex was assessed with LC-MS-MS and H-1-NMR. H-1-NMR and LC-MS-MS results of iodinated EGCG (I-127-EGCG) show that oxidize iodine reacts electrophilic with aromatic ring. Serum stability results showed that in vitro stability of I-131-EGCG was quite high. It is observed that labeling percentage decreased 83 +/- A 2% at 24th, Partition coefficient results show that the partition coefficient of EGCG was calculated as theoretical partition coefficient = 2.04 +/- A 0.42 and the experimental partition coefficient of I-131-EGCG was found as 1.46 +/- A 0.2. The biodistribution data shown that the maximum uptake of the radioiodinated EGCG was seen in lung and pancreas at 30 min. The blocking assay results indicated that the uptake of I-131-EGCG in lung was not significantly change (0.25, 0.23, and 0.22%ID/g at 30, 60, and 150 min, respectively). Biodistribution data showed no significant uptake in a specific organ of the rat. Hence radiolabeled EGCG is seen in some organs (lung, liver, pancreas, kidney, etc.).