Synthesis, radiolabeling and biodistribution of a new opioid glucuronide derivative: ethyl-morphine glucuronide (em-glu)

In current study, ethyl-morphine (em) was synthesized from the morphine and glucuronidated via enzymatic mechanism. The conjugated glucuronide ethyl-morphine (em-glu) was radiolabeled with ¹³¹I using iodogen method. The quality control studies of radiolabeled compound (¹³¹I-em-glu) were done with Thin Layer Radio Chromatography to confirm the radiolabeling efficiency. Biodistribution studies of ¹³¹I labeled em-glu were run on healthy male Albino Wistar rats. The distribution figures demonstrated that ¹³¹I-em-glu was eliminated through the small intestine, large intestine and accumulated in urinary bladder both receptor blocked and unblocked biodistribution studies. A greater uptake of the radiolabeled substance was observed in the m.pons, hypothalamus and mid brain than in the other branches of the rats’ brains.     

Synthesis of a radioiodinated antiestrogen glucuronide compound (TAM-G)

Tamoxifen [TAM; ([Z]-2-[4-(1,2-diphenyl-1-di-butenyl)-phenoxy]-N,N-dimethylethanamine) has been used as an antiestrogen drug for treatment and prevention of human breast cancer. The aim of this study is conjugation of hydrophilic glucuronic acid to the starting substance TAM and labeling with ¹³¹I using iodogen as oxidizing agent. The reactions are completed in three steps, including enzymatic reaction, with the following sub-steps; preparation of microsomal fraction from rat liver and subsequent purification of UDP-glucuronyl transferase (UDPGT), estimation of protein amount in microsomal samples and glucuronidation reaction. Synthesized glucuronide derivative (TAM-G) was purified using high performance liquid chromatography (HPLC). Mass spectroscopy of cold standard showed that the labeling most probably occurs in ortho position to the aromatic ring containing the ether group of TAM-G as expected. Radiochemical yield of the ¹³¹I labeled TAM-G ([¹³¹I]TAM-G) is determined by using Thin Layer Radio Chromatography (TLRC). The radiopharmaceutical potential of [¹³¹I]TAM-G is examined by biodistribution studies that is run on normal female Albino Wistar rats. According to biodistribution results ¹³¹I labeled TAM-G may be proposed as a new antiestrogen glucuronide imaging agent for breast and uterus.     

In vivo biodistribution of <Superscript>131</Superscript>I labeled bleomycin (BLM) and isomers (A2 and B2) on experimental animal models

Bleomycins (BLMs; BLM, A2, and B2) were labeled with ¹³¹I and radiopharmaceutical potentials were investigated using animal models in this study. Quality control procedures were carried out using thin layer radiochromatography (TLRC), high performance liquid chromatography (HPLC), and liquid chromatography (LC/MS/MS). Labeling yields of radiolabeled BLMs were found to be 90, 68, and 71%, respectively. HPLC chromatograms were taken for BLM and cold iodinated BLM (¹²⁷I-BLM). Five peaks were detected for BLM and three peaks for ¹²⁷I-BLM in the HPLC studies. Two peaks belong to isomers of BLM. The isomers of BLM were purified with using HPLC. Biological activity of BLM was determined on male Albino Wistar rats by biodistribution and scintigraphic studies were performed for BLMs by using New Zelland rabbits. The biodistribution results of ¹³¹I-BLM showed high uptake in the stomach, the bladder, the prostate, the testicle, and the spinal cord in rats. Scintigraphic results on rabbits agrees with that of biodistributional studies on rats. The scintigraphy of radiolabeled isomers (¹³¹I-A2 and ¹³¹I-B2) are similiarly found with that of ¹³¹I-BLM.     

Labeling of acetaminophen with I-131 and biodistribution in rats

The aim of the present study was to label acetaminophen (APAP) with I-131 and to determine its radiopharmaceutical potential in rats. Acetaminophen was labeled with I-131 using the iodogen method. The radiochemical purity of (131)I-APAP was determined by RTLC and paper electrophoresis. The labeling yield was 94 +/- 4%. The biodistribution studies of the labeled compound (specific activity; 56.60 GBq/mmol) were performed in male Albino Wistar rats. The uptake of (131)I-APAP in some organs were determined at different time after injection to the rats. The radioactivity in each organ was counted and the percentage of injected activity per gram of tissue weight (%ID/g) for each organ and blood was calculated. (131)I-APAP uptake in the lung, liver, kidneys, pancreas, blood, stomach and some brain region, were observed. Thus, (131)I-APAP may be radiopharmaceutical for the imaging of the brain.     

Diethylstilbestrol glucuronide (DESG): synthesis, labeling with radioiodine and in vivo/in vitro evaluations

Diethylstilbestrol (DES) is a synthetic non-steroidal estrogen, pharmacologic effects of which resemble natural estrons; today it is being used to treat some types of postmenopausal breast cancer and advanced prostate cancer. The aim of current study is conjugation of glucuronic acid (G) to DES and to evaluate radiopharmaceutical potential of this estrogen glucuronide derivative (DESG) which is specific to β glucuronidase enzyme consisting tumor cells. Taking into consideration the compatibility to the chemical structures of the synthesized product, ¹³¹I and ¹²⁵I were chosen as the appropriate radionuclides and DESG was labeled with these radionuclides utilizing iodogen method. The radiochemical yields of ^125/131I-DESG were over 90 % according to thin layer radio chromatography method. The biodistribution of ¹³¹I-DESG in healthy female Wistar Albino rats has been investigated and the range of the breast/blood and breast/muscle ratios were approximately 2 and 13 in 240 min for ER unsaturated studies. Effects of the radioiodinated DES and DESG on the cells were examined using MCF-7, A-549, Caco-2 cell lines. ¹²⁵I-DESG has higher incorporation percentages than ¹²⁵I-DES on MCF-7 cells. The radioiodinated DESG has the desired radiopharmaceutical properties which could be candidate radiopharmaceuticals for diagnosis and especially radionuclide therapy of breast tumors.     

Labeling of apigenin with 131I and bioactivity of 131I-apigenin in male and female rats

Apigenin (4′,5,7-trihydroxyflavone), one of the most common flavonoids, has been shown to possess a variety of biological activities including tumor growth inhibition and chemopreventation. In the present study, apigenin was labeled with ¹³¹I using iodogen method and investigated of its bioactivity. Radiolabeling yield is 98±0.2%, as determined by radio thin layer chromatography (RTLC), electrophoresis and radio high performance liquid chromatography (RHPLC). Besides, structure analysis of synthesized cold iodoapigenin complex were assessed with LCMS/MS and ¹H-NMR. Results of in vitro study indicated a high stability (3 hours) in human serum. Biodistrubition studies are performed in male and female albino Wistar rats. Biodistribution data related to the male rats showed significant uptake in the small intestine. The female rats biodistribution results indicated that the uptake of ¹³¹I-apigenin was high in the intestine and uterus.     

99mTc-glucoheptonate-guanine: Synthesis, biodistribution and imaging in animals

The aim of the current study was to design a nucleotide-based radiopharmaceutical which could be labeled with ^99mTc and to investigate its radiopharmaceutical efficiency and stability. GHA (glucoheptonate) was used as bifunctional chelate. GHA was labeled with ^99mTc by SnCl₂ reduction method first, and then G (guanine) was conjugated with ^99mTc-GHA at 90 °C. In order to determine its radiopharmaceutical stability, thin layer radio chromatography (TLRC) and electrophoresis were employed. In addition, the results were confirmed using high performance liquid radio chromatography (HPLRC). Scintigraphic imaging was performed on rats with mammary tumors, while tissue distribution was determined on Albino Wistar rats. Labeling yield was found to be over 95% and the labeled complex maintained its stability during the study period. The lipophilicity of the ^99mTc-GHG was measured and the partition coefficient (logP) of the labeled compound calculated. The results demonstrated that the uptake of ^99mTc-GHG (^99mTc-glucoheptonate-guanine) reached its maximum at 3 hours p.i. in stomach and intestines. Main way of excretion was renal. Hepatobiliary excretion was also observed. In conclusion, ^99mTc-GHG may be useful as a nucleotide-based radiopharmaceutical for in vivo applications.     

Labeling of famotidine with 99mTc and biodistribution studies on rats

Famotidine, a gastrointestinal drug was labeled with ^99mTc and its radiopharmaceutical potential was observed on male Albino Wistar rats. Labeling yield was over 95%. Average specific activity and n-octanol/water partition coefficient (lipophilicity) were approximately 74 MBq/mg-0.66 GBq/mg and 3.4, respectively. Biodistribution studies were performed on Albino Wistar rats. The activity per gram tissue was calculated and time-activity curves were generated. The majority of the activity was observed in stomach, small intestines and kidneys. Liver and kidneys showed lower uptake compared to other H₂-receptor rich tissues. Results show that ^99mTc-famotidine is H₂receptor specific. This revised version was published online in July 2006 with corrections to the Cover Date.     

Labeling of Sertraline with 131I and investigation of its radiopharmaceutical potential

Sertraline is an antidepressant drug. Sertraline was labeled with ¹³¹I by using iodogen method. Labeling yield was 85–90% and specific activity was approximately 64.75 GBq/mmol. The purification of radioiodinated Sertraline was performed by Sep Pak C-18 plus and the radiochemical purity was determined to be over 99%. Biodistribution studies were carried out by male Albino Wistar rats. The percentage of injected radioactivity per gram of tissue was calculated, and these data versus time curves were generated for organs and brain regions. The results showed that ¹³¹I labeled Sertraline may be a promising radiopharmaceutical for the investigation of serotonin 5-HT receptor functions of brain.     

Synthesis of <Superscript>131</Superscript>I labeled estrone derivatives and biodistribution studies on rats

Summary The aim of this study is to synthesize novel ¹³¹I labeled estrone derivatives that may have therapeutical potentials on Estrogen Receptor rich tumors. Two radiolabeled estrone derivatives, [¹³¹I]2-iodo-3-methoxy-estra-1,3,5-trien-17-one and [¹³¹I]4-iodo-3-methoxy-estra-1,3,5-trien-17-one were synthesized. Ether amino estrone derivatives were obtained from estrone in three steps by means of diazonium compounds. Tissue distribution studies exhibited receptor-mediated uptake in target organs in female Albino Wistar rats. Maximum uptakes for 2-iodo[¹³¹I]-3-methoxy-estrone are in stomach, pancreas, intestines and uterus. A similar biodistribution profile was obtained for 4-iodo[¹³¹I]-3-methoxy-estrone. However 2-iodo-3-methoxy-estra-1,3,5-trien-17-one has higher uptake in stomach, kidneys, pancreas, and intestines than 4-iodo-derivative.     

<Superscript>99m</Superscript>Tc-exorphin C: A new peptide radiopharmaceutical for tumor imaging

Summary The aim of this study was to label exorphin C with ^99mTc and to examine its usefulness as opioid receptor binding radiopharmaceutical in Albino Wistar rats. Exorphin C, which is a peptide with 5 aminoacids, was labeled with ^99mTc using glucoheptonate (GH) as a bifunctional chelating agent. Labeling efficiency was higher than 98%. The compound was stable for at least 5 hours at room temperature. Mammary tumor bearing Albino Wistar rats were imaged using gamma-camera. Biodistribution studies were also performed. Results demonstrated that ^99mTc-glucoheptonate-exorphin C (^99mTc-GE) analogs may be useful as a new class of receptor-binding peptides for the diagnosis and therapy of some cancer diseases related with opioid receptor-expressing tissues.     

Synthesis of a 99mTc labeled estrogen-derivative and the determination of its radiopharmaceutical potential on rats

An estrogen derivative 1-(3, 17-α-estradiolyl propin-1-yl-3-(1,4,8,11-tetraazacyclotetradecyl)-propanate (ESTACPA) was synthesized. The product was purified by HPLC and characterized by NMR and IR spectroscopy. The synthesized compound was labeled with ^99mTc. The biodistribution studies were performed on female Albino Wistar rats. The rats were sacrificed and their organs were removed. The radioactivities of the organs were counted using a gamma-counter. The activity per gram tissue was calculated and time versus activity curves were generated. The ^99mTc-ESTACPA uptake by the uterus and ovary such as ER-rich tissues, were observed. The pancreas and stomach also showed a significant uptake. This revised version was published online in July 2006 with corrections to the Cover Date.     

Synthesis of DTPA-attached estradiol derivative and determination of its radiopharmaceutical potential

Summary An estrogen derivative, β-estradiol or 1,3,5,(10)-estratriene-3,17β-diol) attached to diethylenetriamine pentaacetic acid (DTPA) was synthesized in six experimental steps. At the end of these steps, a DTPA-attached estradiol derivative called deoxy-demethyl homoestradiolyl-diethylenetriamine-pentaacetic acid (ESTDTPA) was obtained. The synthesized compounds were labeled with ^99mTc. Thin layer radio chromatography (TLRC) was used to determine radiochemical yields and stabilities.Structural investigations confirmed the structures. The labeling yield was satisfactory (about 95%), and ^99mTc-ESTDPTA was stable in neutral medium at room temperature for 5 hours. Biodistribution studies were performed on normal and DMBA-induced, tumor bearing female Albino Wistar rats. The activity per gram tissue was calculated, and time-activity curves were plotted. ESTDTPA uptake by uterus reached a level of 20.73% dose/g, showing a maximum within 5 minutes after injection. Ovary and breast showed similar biodistribution profiles. The kidneys, which are the primary organs of metabolism and excretion of estrogen, showed a high ^99mTc-ESTDTPA uptake. The imaging studies were performed on normal and tumor bearing female Albino Wistar rats using a Camstar XR/T gamma-camera. Gamma-scintigraphy studies showed that tumors could be well visualized in a few minutes and clearly differentiated from other organs, such as bladder and liver by 24 hours.     

An oestrogen-derivative labeled with 99mTc and its radiopharmaceutical potential

An oestrogen derivative 3,17-a-oestradiolyl propyl 1,4,8,11-tetraazacyclotetradecanyl-1-(4-methylbenzoic acid)ester (ESTCPTA) that is 3,17-a-oestradiolyl propinol coupled to 1-(4-methylbenzoic acid)1,4,8,11-tetraazacyclotetradecane (CPTA) was synthesized in five steps. The product was purified by recrystallization in ethyl alcohol, and analysed by NMR and IR spectroscopy. ESTCPTA was labeled with ^99mTc and radio thin layer chromatography (RTLC) and radio-paper electrophoresis were used to determine the radiochemical yields. Specific activity was approximately 23.7 GBq/mmol and the labeling yield was over 95%. The biodistribution studies were performed on female Albino Wistar rats. The rats were sacricified by ether narcotization at certain time intervals and the activity of the organs was counted by a gamma counter. The activity per gram tissue was calculated and time activity curves were generated.     

Biological distribution of iodo-allyl gabapentin and iodo-gabapentin

Gabapentin (GBP) is an anticonvulsant and is widely used in the treatment of epilepsy. In this study, GBP and an allyl derivative of GBP were radioiodinated with ¹³¹I using the iodogen method; then their radiopharmaceutical potential in rats and rabbits was investigated. The radiochemical purity of ¹³¹I-GBP and its derivatives was determined by RTLC. The labeling yield was 95±2%. Biological evaluation was performed in normal rats and rabbits. Labeled compounds were intravenously injected into two rabbits via the ear vein after anesthetizing. The dynamic and static scintigrams were obtained using a gamma camera at different time. Then the labeled compounds were administered intravenously into the rats. The distribution was studied by counting the radioactivity in the removed organs. The results of biodistribution in the rats showed the clearance of ¹³¹I-ALGBP was faster than ¹³¹I-GBP. On the other hand, the uptake of ¹³¹I-ALGBP in the brain was higher than ¹³¹I-GBP at 60 minutes.     

The influence of stereoisomerism on the biological behavior of 99mTc labeled penicillamine

The aim of this study is to investigate stereoisomeric behavior of penicillamine and the effect of temperature on labeling. In addition, it was explored how stereoisomerism affected biological behavior of them. In the present work, D- and L-enantiomers of penicillamine(D-PA, L-PA) were labeled with ^99mTc using SnCl₂ as reducing agent and their radiopharmaceutical potentials were investigated. Quality control procedures were carried out using thin layer radiochromatography (TLRC), electrophoresis and high performance liquid radiochromatography (HPLRC). HPRLC chromatograms showed two peaks for ^99mTc-D-PA, while a single peak was observed for ^99mTc-L-PA at room temperature. However, the single peak was observed at 90 °C for both isomers. Labeling yields of each isomer were found to be over 98%. Biological activity of these complexes was determined on male Albino Wistar rats by biodistribution studies. While the biodistribution result of ^99mTc-D-PA showed high uptake in the liver, maximum uptake of ^99mTc-L-PA was observed in the kidneys. Both two complexes were cleared rapidly from the blood, mainly by the renal system. Since the activity concentration of ^99mTc-D-PA at the 30th minute in the kidneys and the liver reached a maximum value and at the 120th minute, it was removed by renal and hepatobiliary excretion. As a result, it can be concluded that stereoisomerism affect not only the chemical behavior, but also differs their biological behavior of these compounds.     

Radiolabeling of codeine with 131I and its biodistribution in rats

Codeine which was extracted from dry capsules of the opium poppy (Papaver somniferum) was purified by HPLC (High Performance Liquid Chromatography) and characterized by NMR (Nuclear Magnetic Resonance) and IR (Infrared) spectroscopy techniques. The purified compound was labeled with ¹³¹I and biodistribution studies were performed in rats. Radioiodinated codeine distributed uniformly in the cerebellum, m.pons, striatum and hypothalamus while the other branch of brain and Stomach, urinary bladder, and small intestine uptakes were significantly higher than other tissues.     

Synthesis, radiolabeling and in vivo biodistribution of diethylstilbestrol phosphate derivative (DES-P)

Diethylstilbestrol (DES) is a well known, nonsteroidal estrogen with high affinity for the estrogen receptor (ER). Today DES is used to treat breast and prostate cancers. A phosphate derivative of DES [Diethylstilbestrol diphosphate (DES-P)] which is specific to tumor cells consisting alkaline phosphatase enzyme was synthesized and labeled with ^99mTc using tin chloride as reducing agent. In vivo biological activity of ^99mTc labeled diethylstilbestrol phosphate compound (^99mTc-DES-P) was examined by biodistribution studies on Wistar Albino rats. Statistical evaluation was performed using SPSS 13 program. The percentage (%) radiolabeling yield of ^99mTc-DES-P and quality control studies were done by Thin Layer Radio Chromatography (TLRC). Results showed that, ^99mTc-DES-P may be proposed as an imaging agent for ER enriched tumors such as uterus and prostate and their metastases in bones.     

Interaction between green tea extract and 99mTc-pertechnetate on in vivo distribution

People drink various types of tea without knowing the side effects of biological and chemical contents and radiopharmaceutical interactions. In current study, it is aimed to evaluate the effects of green tea extract in different extraction solvents on the radiolabeling of the blood constituents with ^99mTc and on the biodistribution of radiopharmaceutical sodium pertechnetate (Na^99mTcO₄) in male Wistar Albino rats. The extraction of green tea was performed in different solvents. Biodistribution studies were performed on male rats which were treated via gavage with green tea extract in different extraction solvents or saline (0.9 % NaCl) as a control group for 7 days. The radiolabeling of blood constituents performed incubating with SnCl₂ and ^99mTc. According to experimental results, radiolabeling blood components with ^99mTc were not modified in the usage of the different extraction solvents for green tea extraction, but a significant alteration (P < 0.05) of biodistribution of Na^99mTcO₄ was observed after treatment with green tea extract in distilled water. Although there is no considerable effect on radiolabeling of blood components, there is an outstanding change on the biodistribution studies especially with green tea extract in distilled water. The identified change monitored in this study may cause to reduce the risk of misdiagnosis and/or avoid the repetition of the examinations in nuclear medicine.     

Distribution of 131I-labeled recombinant human erythropoietin in maternal and fetal organs following intravenous administration in pregnant rats

The aim of the present study was to demonstrate the possible transplacental transmission of ¹³¹I labeled recombinant human erythropoietin (¹³¹I-rh-EPO) in pregnant rats and its distribution through maternal and fetal organs. Six Wistar Albino Rats in their pregnancy of 18 days were used ¹³¹I labeled recombinant human erythropoietin (specific activity = 2.4 μCi/IU) was injected into the tail vein of rats. After 30 minutes labeled erythropoietin infusion maternal stomach, kidney, lung, liver, brain and heart as well as fetus were removed. Then, the same organs were removed from each fetus. Measuring weight of maternal and fetal organs as well as placenta were followed by radioactivity count via Cd(Te) detector. ¹³¹I labeled recombinant human erythropoietin was found to be able to pass rat placenta and its distribution order in fetal organs was similar to those of maternal organs. Besides, as measurements were performed closer to cornu uteri, uptakes were decreasing in every fetus and its corresponding placenta.