Hayal Ozkilic

Detecting inflammation with 131I-labeled ornidazole.

The aim of this study was to demonstrate the accumulation of 131I-labeled ornidazole (131I-ORN) in experimental abscesses. 131I-ORN was prepared by electrophilic radioiodination of ORN, using radioiodide in the presence of Iodogen. An in vivo inflammation model was prepared by intramuscular injection of turpentine into the thigh of rabbits. Four days later 131I-ORN was intravenously administered to rabbits. Serial scintigrams were performed at different periods, using a Sophy DX Gamma Camera. 131I-ORN was visualized at 10 min after injection. 131I-ORN was also administered intraperitoneally to rats with turpentine-induced inflammation, for quantitative biodistribution studies. Counts of selected tissues were taken by a NaI(Tl) scintillation detector (gamma counter) after rats were decapitated. The target-to-non-target muscle ratios were 2.5, 2.6, 2.9 and 1.9 at 1, 3, 5 and 24 h, respectively.

Effect of pulsatile flow during cardiopulmonary bypass on thyroid hormone metabolism

Changes in thyroid hormone levels during and after cardiopulmonary bypass (CPB) are well documented. However, little is known about the effects of pulsatile flow during CPB on thyroid hormone metabolism. To examine the effect of flow pattern, a prospective study was carried out using 30 patients undergoing coronary artery bypass grafting. Fifteen patients had pulsatile flow during CPB and 15, nonpulsatile flow. Serum samples were obtained preoperatively, during bypass, and at 2 and 24 hours postoperatively. Thyroid-stimulating hormone, thyroxine (T4), triiodothyronine (T3), free T4, and free T3 levels were measured by radioimmunoassay. All measured hormone levels except free T4 and thyroid-stimulating hormone decreased after the initiation of CPB. There were no differences in preoperative values between the two groups. However, levels of T3 and free T3 during and after CPB showed a significant difference between the two groups, with a smaller decrease in patients in whom pulsatile flow was used during bypass (p < 0.05). Thyroxine, and thyroid-stimulating hormone free T4 values showed no difference between the two groups at any sampling time. These data provide support for the use of pulsatile flow during CPB to establish a more physiologic state and maintain better thyroid hormone metabolism.

Plasma and Bronchoalveolar Lavage Fluid Levels of Endothelin-1 in Patients with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension

Background: Secondary pulmonary hypertension (PH) and cor pulmonale are the major clinical cardiovascular complications affecting prognosis in patients with chronic obstructive pulmonary disease (COPD). It is also known that endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by the pulmonary vascular endothelium, and ET-1 may be implicated in the pathogenesis of PH. Objectives: The purpose of this study was to investigate the presence of ET-1 in patients with COPD and to assess the correlation of ET-1 levels in the plasma and bronchoalveolar lavage (BAL) fluid (BALF) in COPD patients with or without PH. Methods: Twenty-two patients with COPD and 15 healthy controls were enrolled in the study. Peripheral venous blood samples were collected in all patients and controls. BAL was obtained in COPD patients, and ET-1 levels were measured by radioimmunoassay in all plasma and BALF samples. Results: Plasma ET-1 levels were 2.46 ± 0.55 and 1.70 ± 0.42 pmol/dl in patients with COPD and controls, respectively (p < 0.0001). Sixteen of the 22 patients with COPD (73%) had PH established by echocardiography. The ET-1 level in these patients amounted to 2.59 ± 0.50 pmol/dl, and it was 2.10 ± 0.54 pmol/dl in 6 patients with COPD without PH. In COPD patients with and without PH, BALF ET-1 levels were 0.19 ± 0.08 and 0.24 ± 0.01 pmol/dl, respectively (p > 0.05). Conclusions: These results suggest that ET-1 is detectable in both the peripheral blood and BALF of COPD patients, but the levels do not statistically differ between patients with and without PH.

Long-term evaluation of chromosomal breakages after radioisotope synovectomy for treatment of target joints in patients with haemophilia

Summary.  Radioisotope synovectomy (RS) is defined as the intra‐articular injection of radioisotopic agents with the aim of fibrosis on hypertrophic synovium in the target joint. The aim of this study was to investigate genotoxic effects on lymphocytes and malign transformation induced by Yttrium90 (Y90) and Rhenium186 (Re186) in children with haemophilia undergone RS. Forty haemophilia patients were enrolled. The mean age was 16.4 ± 6.2 years (range: 8–40). Y90 was used for knees, Re186 was used for other joints. For safety, cytogenetic analysis was performed to determine potential chromosomal changes after RS procedure at three different time points as prior to procedure, 3rd day and 90th day. For the stimulation of chromosomal breakages, diepoxybutane was used (DEB test). Chromosomal breakages (CBs) were found in 23 patients (67.6%) prior to RS. We have found CBs additionally in nine of 11 patients who had no CBs prior to RS after 3 days of radioisotope exposure. At that time, the patients who had CBs were 29 (85.2%). At day 90, only 21 patients revealed (61.7%) CBs. The mean frequency of CBs slightly but not significantly increased in the 3rd day. However, there was a significant decreasing trend between 3rd and 90th days. Radioisotope synovectomy with Y90 and Re186 does not seem to induce the genotoxic effects significantly on peripheral blood lymphocytes. However, CBs even after one year in the re‐evaluation of four patients, significant decrease in the number of CBs between the 3rd and 90th days and de novo CBs after exposure may be accepted as warning signals for young population. It should also be pointed out that families and patients be informed properly related with historical and potential dangers of radioisotopic agents.

(99m) Tc-Doxycycline hyclate: a new radiolabeled antibiotic for bacterial infection imaging.

Radiolabeled antibiotics are promising radiopharmaceuticals for the precise diagnosis and detection of infectious lesions. Doxycycline Hyclate (DOX) was chosen to investigate new (99m) Tc-labeled antibacterial agent. Ready to use freeze dry kits were formulated with optimum labeling conditions. Human serum stability, sterility, and pyrogenicity of kits were estimated, and gamma scintigraphy, in vivo biodistribution, and histopathological studies with bacterial infected rats were performed. DOX were successfully labeled by (99m) Tc with high radiochemical purity, and the labeled compound was stable in human serum. Kits were sterile, pyrogen-free, and stable up to 6 months. Static images depicted rapid distribution throughout the body and high uptake in bacterial infected thigh muscle. The uptake ratios of radiopharmaceuticals in infected thigh muscle were found above 2 up to 5 h. Five hours after injection, the rats were sacrificed, and biodistribution was determined. Samples of bacterial infected muscle, healthy muscle, blood, liver, spleen, lung, kidney, stomach, intestine, urine and heart were weighed, and the radioactivity was measured by using a gamma counter. The %ID/g of (99m) Tc-DOX was found 0.23 ± 0.06 for infected thigh muscle. According to the imaging, biodistribution, and histopathological studies, the promising characteristics of (99m) Tc-DOX make the new radiopharmaceutical valuable to examine for future studies.

The Absorption of 99mTc-alendronate Given by Rectal Route in Rabbits

Alendronate sodium (ALD) is a bisphosphonate medication used in the treatment and prevention of osteoporosis. Absorption of ALD as oral formulation is very poor (0.5%–1%). Its bioavailability can decrease with food effect. It has some gastrointestinal adverse effects such as gastritis, gastric ulcer, and esophagitis. The aim of this study was to develop a rectal formulation of ALD as an alternative to oral route and to investigate the absorption of it by using gamma scintigraphy. For this reason, ALD was labeled with Technetium-99m (99mTc) by direct method. The radiochemical characterization of the 99mTc-ALD was carried out by paper chromatography, thin layer chromatography, and electrophoresis methods. The labeling efficiency of 99mTc-ALD was found 99% without significant changes until 6 h postlabeling at room temperature. The rectal suppositories containing 99mTc-ALD were prepared by fusion method using polyethylene glycol (PEG) 1500. The 99mTc-labeled ALD suppositories were administrated to rabbits by rectal route. Serial scintigrams over all bodies of the rabbits were obtained at different time intervals using a gamma camera. We found that the rectal absorption of 99mTc-ALD from suppository formulation was possible. According to our results, this formulation of ALD can be suggested for the therapy of osteoporosis as an alternative route.

A correlative study between 99mTc-ESTCPTA and 99mTc-MIBI in rats.

Tissue distribution of the 99mTc labeled derivative of the estrogen compound 3,17-alpha-estradiolyl propyl 1,4,8,11-tetraazacyclotetradecanyl-l-(4-methylbenzoic acid) ester (ESTCPTA), which has an 3,17-alpha-estradiolyl propinol coupled to l-(4-methylbenzoic acid)1,4,8,11-tetraazacyclotetradecane (CPTA), was compared to 99mTc-MIBI (methoxyisobutyl isonitrile) in female Albino Wistar rats. Tissues of interest included lung, liver, heart, kidneys, spleen, stomach, intestines, pancreas, muscle, blood, breast, ovary, fat, and uterus. 99mTc-ESTCPTA uptake by the uterus and ovary, as ER-rich tissues, was highly selective. Maximum uptakes for 99mTc-MIBI and 99mTc-ESTCPTA are 90 min in breast, ovary and uterus. The pancreas also showed significant receptor saturated and unsaturated ratios for 99mTc-ESTCPTA. Results are sufficiently encouraging to generate further evaluation of these and related compounds as possible estrogen receptor based tumor imaging and therapeutic agents in estrogen-rich tissues.

Evaluation of 99mTc-amoxicillin sodium as an infection imaging agent in bacterially infected and sterile inflamed rats

Bacterial infection is one of the major causes of morbidity and mortality especially in developing countries. The aim of this study was to develop a new radiopharmaceutical for imaging infection. The labeling conditions were optimized, and lyophilized kits were developed for instant preparing. The stability of 99mTc-AMOX in human serum was identified, sterility and pyrogenicity of the radiopharmaceutical were estimated, gamma scintigraphy and in vivo biodistribution with infected rats were investigated. The promising properties of 99mTc-AMOX combined with the development of reliable and instant lyophilized kit afford the opportunity of inflammatory process imaging.

Labeling of diazepam with iodine-131

Diazepam, which aims at benzodiazepine receptors and can be used as a specific SPECT agent has been labeled with [131I]2-iododiazepam (2-IDZ) was obtained in 50% HCl medium and [131I]2′-iododiazepam (2′-IDZ) was prepared by the iodogen method. The products were purified by passing through a Dowex-1 anion-exchange column.

Gamma scintigraphy and biodistribution of 99mTc‐cefotaxime sodium in preclinical models of bacterial infection and sterile inflammation

(99m)Tc-cefotaxime sodium ((99m)Tc-CEF) was developed and standardized under varying conditions of reducing and antioxidant agent concentration, pH, radioactivity dose, and reducing agent type. Labeling studies were performed by changing the selected parameters one by one, and optimum labeling conditions were determined. After observing the conditions for maximum labeling efficiency and stability, lyophilized freeze dry kits were prepared accordingly. Simple method for radiolabeling of CEF with (99m)Tc has been developed and standardized. Labeling efficiency of (99m)Tc-CEF was assessed by both radio thin-layer chromatography and radio high-performance liquid chromatography and found higher than 90%. The labeled compound was found to be stable in saline and human serum up to 24 h. Two different freeze dry kits were developed and evaluated. Based on the data obtained from this study, both products were stable for 6 months with high labeling efficiency. The prepared cold kit was found sterile and pyrogen free. The bacterial infection and sterile inflammation imaging capacity of (99m)Tc-CEF was evaluated. Based on the in vivo studies, (99m)Tc-CEF has higher uptake in infected and inflamed thigh muscle than healthy thigh muscle.