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K Ozker

Publications and source records attributed to K Ozker.

27 records · Page 2Linked to original sources

Selective incorporation of 111In-labeled PHOTOFRIN by glioma tissue in vivo.

The use of PHOTOFRIN for photodynamic therapy of human gliomas has been studied by i.v. administration and laser photosensitization. Defining the uptake of PHOTOFRIN in the patient's tumor in comparison with the surrounding normal brain tissue is highly desirable for patient selection and study of in vivo kinetics. We utilized a non-invasive approach to the detection of PHOTOFRIN uptake in brain tumors with 111In-oxine radiolabeled PHOTOFRIN and external imaging and quantitation using a gamma camera. Biodistribution of 111In-labeled PHOTOFRIN in 13 organs was determined in four dogs and 15 mice with gliomas. 99mTc-DTPA was used as a control for nonspecific uptake. The greatest concentration of 111In-PHOTOFRIN in the brain tumor occurred at 24 hours post i.v. administration. The brain tumor PHOTOFRIN uptake was seven times greater than that of normal brain. The decreased blood background at 72 hours made this the optimum time for imaging. Specific tumor tissue uptake of 111In-PHOTOFRIN occurred, well beyond that resulting from blood-brain-barrier (BBB) breakdown.

Animals↗

Technetium-99m-N,N-ethylenedicysteine--a comparative study of renal scintigraphy with technetium-99m-MAG3 and iodine-131-OIH in patients with obstructive renal disease.

UNLABELLED: Technetium-99m-labeled N,N-ethylenedicysteine (99mTc-EC) is a new renal imaging agent introduced as an alternative for 99mTc-labeled mercaptoacetyltriglycine (99mTc-MAG3), with similar renal excretion characteristics. To evaluate the diagnostic characteristics of this agent, a gamma camera study was performed. METHODS: Sixteen patients with obstructive renal disease and six normal controls were injected with 90 to 110 MBq of 99mTc-EC and 7.4 MBq 131I-labeled orthoiodohippurate (OIH). Serial images were obtained during 20 min for 99mTc-EC and 30 min for OIH. The study was repeated using 90 to 110 MBq 99mTc-MAG3 during the same week. RESULTS: Renograms, functional ratios and urinary excretion patterns of all three agents were similar. The mean time to peak activity values for OIH, 99mTc-EC and 99mTc-MAG3 were 4.25 +/- 0.37 min, 4.39 +/- 0.32 min and 4.00 +/- 0.24 min, respectively. The time from peak to 50% activity values for OIH, 99mTc-EC and 99mTc-MAG3 were 5.48 +/- 0.80 min, 6.93 +/- 0.69 min and 7.33 +/- 0.85 min, respectively. CONCLUSION: It is concluded that 99mTc-EC has excellent imaging characteristics and similar excretion properties to OIH. The advantages of 99mTc-EC over 99mTc-MAG3 are lower hepatobiliary uptake and simplicity of preparation.

Adult↗

Reversible inhibition of urea exchange in rat hepatocytes.

Urea exchange is enhanced in renal collecting duct cells and erythrocytes by transporters which can be inhibited by phloretin and urea analogs such as thiourea. In this study, evidence for a comparable transporter was found in rat livers perfused with solutions which contained no red cells and in suspensions of hepatocytes. Bolus injections containing 125I-albumin (intravascular indicator), 99mTc-DTPA (extracellular indicator), 3HOH (water indicator), and [14C]urea were administered into the portal vein and fluid was collected from the hepatic vein. Under control conditions, [14C]urea and 3HOH emerged from the hepatic vein at nearly the same rate. However when the perfusate contained 2.5 mM phloretin (equivalent to 0.058 mM phloretin not bound to albumin), the amount of [14C]urea which had been recovered in the hepatic venous outflow by the time of peak 125I-albumin concentrations exceeded 3HOH recovery by a factor of 2.31 +/- 0.23 (n = 7). When the perfusate contained 200 mM thiourea, the comparable recovery of [14C]urea from the hepatic veins exceeded that of 3HOH by a factor of 3.48 +/- 0.44 (n = 7). These effects were at least partially reversible and suggested inhibition of urea transporters in hepatocytes. This conclusion was supported by studies of unloading of [14C]urea from hepatocytes which were exposed to unlabeled solutions: in the presence of phloretin, the amount of [14C]urea remaining within hepatocytes at 4 s was approximately twice that remaining in hepatocytes which had not been exposed to phloretin. Rapid transport of urea out of hepatocytes may increase urea synthesis and minimize cellular swelling due to urea accumulation.

Animals↗

Kinetics of urea exchange in air-filled and fluid-filled rat lungs.

Urea has been used as an indicator for estimating 1) the dilution of epithelial lining fluid (ELF) that occurs during bronchoalveolar lavage (BAL) and 2) the permeability-surface area product (PS) of the pulmonary endothelium to this solute. Because relatively little is known about how urea equilibrates with fluid in the lung tissues and airspaces, we have undertaken a study of the kinetics of movement from the vasculature into the tissues of isolated, perfused rat lungs. Although instillation of 5 ml of 154 mM saline into the airspaces of this preparation increased the calculated extravascular volume of 3HOH from 0.64 +/- 0.23 to 2.10 +/- 0.58 ml (SE, n = 6) during a single transit through the pulmonary circulation, it did not have a detectable effect on the distribution of [14C]urea in the lung tissues. However, leakage of [14C]urea into saline within the airspaces was detected during constant infusions: concentrations in the airspace fluid reached 1.1 +/- 0.2% of those in the perfusate by 90 s and 1.90 +/- 0.2% at 120 s, levels that would significantly reduce estimates of the dilution of ELF by BAL. In contrast, concentrations of 99mTc-diethylenetriaminepentaacetic acetic acid (DTPA) in the airspaces remained < 0.2% of those in the perfusate, suggesting that 99mTc-DTPA may be a superior indicator for estimating dilution of ELF by BAL.(ABSTRACT TRUNCATED AT 250 WORDS)

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99mTc-gentamicin: chemical and biological evaluation.

99mTc-Gentamicin complex, a new agent for renal studies, is prepared by the reduction of pertechnetate by stannous chloride. Organ distribution in rats and paper chromatography with Whatman 3MM paper [developed in n-butanol, acetic acid, and water (4:1:1)] were favored as analytical tools for determination of labeling parameters of 99mTc-Gentamicin. A higher concentration of stannous ion is responsible for the formation of insoluble technetium species which concentrate in the liver. The mean kidney: liver ratio of 10.4:1 was obtained 1 h after injection. This confirms that scintigraphic delineation of kidneys is highly satisfactory.

Animals↗

Breast carcinoma cell uptake and biodistribution of technetium-99m-carboxymethyl benzylamide dextran.

Carboxymethyl Benzylamide Dextran (CMDB7) displayed an in vitro growth inhibitory activity on breast tumor cells. CMDB7 is able to disrupt the interaction of angiogenic growth factors (FGF2, TGF beta and PDGF) with their membrane receptors. This compound blocks the angiogenesis of MDA-MB435 carcinoma xenografted in mammary fat pad and their lung metastases in nude mice. In this work, we studied the uptake of CMDB7 labeled with 99mTc in cultured human breast cancer MCF-7 cell line and the highly tumorigenic MCF-7ras cell line (Ha-ras-transfected MCF-7 cells) and the in vivo distribution in MCF-7ras tumor-bearing mice. The 99mTc-CMDB7 are stable and the intracellular concentration is time-dependent and reaches a plateau at 180 minutes. 99mTc CMDB7 uptake is much higher in MCF-7ras cells than MCF-7 cells. Since CMDB7 is internalized and could also inhibit cell proliferation by acting at nuclear sites, we investigated the MCF-7ras nuclear localization after cell fractionation. Cell fractionation revealed a cytoplasmic and nuclear internalization of CMDB7. The tumor uptakes of 99mTc-CMDB7 were 0.34%, 0.72% and 0.62% of the administrated doses per gram of tumor tissue at 1 hour, 3 hour and 5 hours respectively after their injection. The blood clearance of 99mTc CMDB7 was very rapid and the liver, spleen and kidney uptakes were very weak. These results confirm the absence of toxicity of CMDB7 and the usefulness of CMDB7 in cancer therapy by targeting breast tumors.

Animals↗