Comparison of the radiopharmaceutical potentials of dithizone radiolabeled with 131I and with 99mTc

In this study, dithizone (diphenylthiocarbazone) has been separately radiolabeled with ¹³¹I and with ^99mTc for preliminarily testing their radiopharmaceutical potentials on male albino rabbits. ¹³¹I-dithizone and ^99mTc-dithizone were intravenously injected to rabbits via their ear veins after anesthetizing with a mixture of Alfazyne and Alfamine (Serva) to determine their dynamic and static statuses in the metabolism. Also, ^99mTc as pertechnetate and ¹³¹I as iodate were administered to rabbits as controls. Dynamic and static scintigrams were obtained using a gamma camera (Diacan Instruments). Dynamic scintigrams were obtained over the first half hour with frames of 1 minute following the administrations of the labeled compounds. Static images were obtained from posterior projection at different time intervals up to about 3 hours following the administration of the radiolabeled compounds. ^99mTc-dithizone was significantly uptaken by the pancreas in contrast to free ^99mTc. In the case of ¹³¹I-dithizone, the distribution of ¹³¹I activity in the metabolism was clearly different than the case of free ¹³¹I and the uptake of ¹³¹I-dithizone at the pancreas zone was also significant. These preliminary tests have clearly indicated that especially ^99mTc-dithizone has a significant potential to be used as a pancreatic radiopharmaceutical.     

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.     

Could be radiolabeled flavonoid used to evaluate infection?

The aim of this study was to determine whether [¹³¹I]apigenin is a powerful and discrimination infection from inflammation for scintigraphic imaging. The study was carried out in inflamed rats with Staphylococcus aureus (S. aureus) and sterile inflamed rats with turpentine oil. Biodistribution study of [¹³¹I]apigenin was performed in the rats. Apigenin was labeled with ¹³¹I by iodogen method. Obtained [¹³¹I]apigenin with high yield (98%) was injected i.v. to both group rats. The results were expressed as the percent uptake of injected dose per gram of organ (%ID/g), the bacterial infected and sterile inflamed muscles. Binding of [¹³¹I]apigenin to the infected thigh muscle (target muscle = T) and normal thigh muscle (non-target muscle = NT) ratio (T/NT = 4.51 at 15 min) was higher than binding to bacterial inflamed muscle (T/NT = 2.25 at 15 min) of rats. [¹³¹I]apigenin showed good localization in both inflamed tissues. This uptake in the sterile inflamed tissue is higher than bacterial infected tissue. [¹³¹I]apigenin might be useful for imaging of inflamed tissues. However, it is not discriminate sterile inflamed tissue from bacterial infected tissue.     

Immunoaffinity Column Clean-Up and Liquid Chromatography with Post-Column Derivatization for Analysis of Aflatoxins in Traditional Chinese Medicine

A rapid tandem mass spectrometric (MS-MS) method for the quantification of gabapentin (GBP) in human plasma using 4-phenyl-4-aminobutanoic acid as an internal standard (IS) has been developed and validated. The drug and the internal standard were analyzed, by flow injection analysis without chromatographic separation, using a mobile phase of acetonitrile-water-formic acid (50:50:0.025, v/v/v) at a flow rate of 0.1 mL min^?1. The run-cycle time was <3 min injection-to injection. Quantitation was achieved using multiple reaction monitoring (MRM) scan at MRM transitions m/z 172 > 154 and m/z 180 > 117 for GBP and the IS, respectively. Ion suppression study indicated practically no suppressive effect of plasma constituents on the mass ions detection of GBP and IS, when measured in MRM scanning mode. Calibration curves were linear over the concentration range of 0.1–10 μg mL^?1 (r > 0.999) with a limit of quantification of 0.1 μg mL^?1 (RSD%; 7.6 and % DEVs; ?3.0 to +17.0%). Validation data showed that the RSD% values were in the range of 1.85 to 13.06%, whereas, the % DEVs values ranged from ?1.4 to +10.0% indicating good precision and accuracy. Analytical recoveries of GBP from spiked human plasma were in the range of 98.9 to 101.3%. On the other hand, recoveries of GBP from stored human plasma samples were in the range of 100.0 to 107.5% indicating that GBP was stable in plasma, with no appreciable degradation, when stored at ?20 °C. The developed method was applied for GBP monitoring in plasma samples of patients treated with GBP.     

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.     

Preparation and biodistribution of [<Superscript>131</Superscript>I]linezolid in animal model infection and inflammation

Linezolid is the first of new class of antibiotics, the oxazolidinones, and exhibits activity against many gram-positive organisms, including vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, and penicillin-resistant Streptococcus pneumoniae. Aim of the study: Linezolid was to label with I-131 and potential of the radiolabeled antibiotic was to investigate in inflamed rats with S. aureus (S. aureus) and sterile inflamed rats with turpentine oil. Linezolid was labeled with I-131 by iodogen method. Biodistribution of [¹³¹I]linezolid was carried out in bacterial inflamed and sterile inflamed rats. Radiolabeling yield of [¹³¹I]linezolid was determined as 85 ± 1% at pH 2. After injecting of [¹³¹I]linezolid into bacterial inflamed and sterile inflamed rats, radiolabeled linezolid was rapidly removed from the circulation via the kidneys. Binding of [¹³¹I]linezolid to bacterial inflamed muscle (T/NT = 77.48 at 30 min) was five times higher than binding to sterile inflamed muscle (T/NT = 14.87 at 30 min) of rats. [¹³¹I]linezolid showed good localization in bacterial inflamed tissue. It was demonstrated that [¹³¹I]linezolid can be used to detect S. aureus inflammation in rats.     

Synthesis,radiolabeling and biodistribution of morphine glucuronide (mor-glu)

The aim of this study was to synthesize a glucuronide conjugated morphine derivative which could be labeled with ¹³¹I, as a radiopharmaceutical, and to investigate its radiopharmaceutical potential using biodistribution studies in male Albino Wistar rats. Morphine was extracted from dry capsules of the opium poppy (Papaver somniferum L.). It was conjugated with UDP-glucuronic acid by using UDP-glucuronyl transferase (UDPGT) enzyme rich microsomes, purified by high performance liquid chromatography (HPLC) and characterized by nuclear magnetic resonance (NMR), infrared (IR) spectroscopy and liquid chromatography mass spectroscopy (LC-MS/MS). Normal and receptor blockage biodistribution studies were performed in male Albino Wistar rats. The results of the tissue distribution studies showed that ¹³¹I labeled morphine glucuronide (¹³¹I-mor-glu) uptake in the small intestine, large intestine and urinary bladder was higher than in the other tissues of the rats in the blocked receptor and unblocked receptor. A greater uptake of the radio labeled substance was observed in the hypothalamus and mid brain than in the other branches of the rats’ brains.     

Radioiodination of insulin using N-succinimidyl 5-(tributylstannyl)-3-pyridine-carboxylate (SPC) as a bi-functional linker: Synthesis and biodistribution in mice</p> </p>

Summary Insulin receptors are overexpressed on a number of human tumors, leading to significant affinity of insulin to these tumors. It is appealing to receptor-targeted radiotherapy for malignant tumors if insulin is labeled with suitable radionuclide. In this paper, N-succinimidyl 5-(tributylstannyl)-3-pyridinecarboxylate (SPC), a potential bi-functional linker for radioiodination of proteins or peptides, was synthesizedby using 5-bromonicotinic acid as the starting material. Then, with this bi-functional linker, insulin was conjugated with ¹³¹I, and the tissue distribution of the labeled insulin (¹³¹I-SIPC-insulin) in normal mice was investigated. The results showed that insulin ^</span> could be conjugated with¹³¹I using SPC as the linker ^</span> in a labeling yield of40-58%, and with radiochemical purity of more than 98% after purification bySephadex?G-10. Even kept at room temperature for 72 hours, the radiochemical purity of ¹³¹I-SIPC-insulin was still more than 97%, implying that the conjugated insulin was constantly stable in vitro.Meanwhile, in order to evaluate the in vivo stability of the conjugated compounds, insulin was also labeled with ¹³¹I by a direct method using chloramine-T (Ch-T) as the electrophilic agents.Biodistribution of¹³¹I-SIPC-insulinin micesuggested that ¹³¹I could clear rapidly from the blood,mainly excreted by kidney. However, ¹³¹I uptake of mice with¹³¹I-SIPC-insulin in some key organs, especially in thyroid and stomach, were much less (150 or 30 times) than that with the direct labeled insulin (¹³¹I-insulin). Additionally, it was noted that ¹³¹I-SIPC-insulin hasmuch betterinvivo stability than¹³¹I-insulin.</p> </p>     

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.     

Radioiodination and biodistribution of isolated lawsone compound from Lawsonia inermis (henna) leaves extract

Lawsonia inermis (henna) is one of the most effective medicinal plants and it has been using for treatment of wounds and burns for centuries. The using of Henna leaves is very popular for cosmetic as well as medicine in many countries. Henna leaves contain lots of different compounds and lawsone (LW) is the main one. In current study, extraction with bidistillated water of henna leaves was performed and LW was isolated by using high performance liquid chromatography system. Chemical structure of LW was evaluated by nuclear magnetic resonance method. LW was radiolabeled with iodine-131 (¹³¹I) radionuclide which is well known for nuclear imaging and therapy in nuclear medicine by utilizing iodogen method. The yield of radiolabeling of LW (¹³¹I-LW) was calculated as 92.70 ± 4.312 % (n = 10) by thin layer radio chromatography. Its in vivo biological activity was investigated by biodistribution studies which were performed by using healthy female and male Balb/C mice. According to results of biodistribution, uptake of ¹³¹I labeled LW compound in uterus, breast and ovary for female mice and prostate in male mice was higher than other organs in the body.     

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.     

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.     

A study on the separation and distribution of the chemical forms of131I produced from thermal neutron-irradiated tellurium compounds by thin-layer chromatography

The separation and distribution of the chemical forms of¹³¹I produced from thermal neutron-irradiated tellurium compounds were investigated by thin-layer chromatography using alumina as adsorbent and water as developer as well as the effect of iodine carriers added on the distribution of different chemical forms of¹³¹I was studied. The effects of both atmospheric oxygen and light were investigated on the oxidation of carrier-free iodide on the thin-layer plate.     

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.     

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.     

Labelling of some enzymes by electrolytic iodination a comparative study

The effect of the degree of iodination on the enzymatic activity of two enzymes, phospholipase A₂ (fraction k₁) and cathepsin D, was studied. The compounds were labelled with¹³¹I₃ and¹³¹ICI ₂ ^– prepared by electrolysis at a controlled electrode potential. To avoid excessive denaturation of the enzyme, the electrophilic reagent was produced separately and added to the enzyme solution. Unreacted iodine species were removed by means of gel chromatography on Sephadex G-25. Enzymes were also radioiodinated by a chemical method, using chloramine T as oxidant, the results being compared with those obtained by the electrochemical method.Dedicated to the memory of Professor Lado Kosta (1921–1986).     

An alternative intraarterial therapeutic agent for hepatic tumors:131I lipiodol/histoacryl mixture

Lipiodol has excellent retainable ability in hepatoma cells. This agent can be labeled with radioisotope (¹³¹I) and mixed with tissue adhesive (Histoacryl), and then alttached on the lesion of liver by intrahepatic arterial administration. In this study, we attempt to obtain the optimal ratio of Lipiodol to Histoacryl and evaluate the consolidation of blood in vitro and toxicity and biodistribution in vivo. The ratio of¹³¹I Lipiodol/Histoacryl mixture (L/H), concentration of heparin and flow rate of blood are varied by simulating the installation of bloodstream to test the time of consolidation. In addition, the optimal ratios of the L/H mixtures are assessed in vitro in heparinized human blood. According to those results, Lipiodol and Histoacryl mixed with 1∶1 or 2∶1 ratio have an ideal time of 13 to 15 seconds in vitro; in addition, 1.2∶1 ratio is an optimal ratio in the biodistribution study. Interestingly, heparin and acetic acid does not alter the consolidation time, in addition, no variation occurs when varying the flow rate of blood. The consolidation of L/H mixture with blood is incubated in the 37°C, normal saline bath for 24 hours. No dissociation of free¹³¹I is found. The optimal mixture is also injected into the hepatic artery of the Sprague-Dawley rats carrying for 24 hours. No dissociation of free¹³¹I is found. The optimal mixture is also injected into the hepatic artery of the Sprague-Dawley rats carrying hepatocellular carcinoma (NIS1 cell line). Radioactive consolidate is well confined in the tumor without evidence of leakage of the mixture to the lung or distribution of free¹³¹I in the thyroid. In conclusion, this mixture has the merits of both irradiation and embolization of the tumor. The¹³¹I Lipiodol/Histoacryl mixture (1.2∶1) is a promising alternative for intrahepatic arterial administration to treat hepatic tumors. Histoacryl can confine the¹³¹I and, also, embolize the tumor vessels.     

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.     

Importance of double neutron-capture as a second-order reaction interference in NAA

In order to estimate gut absorption by determining tracer concentration in plasma, a technique based on the administration of two stable isotopes of the same element was combined with proton activation analysis. The optimization for the determination of Zr isotopes in biological samples is presented together with the results of a preliminary study on Zr biokinetics in animals. (p,n) reactions on⁹⁰Zr and⁹⁶Zr resulted the most convenient. The obtained minimum detectable quantities are 3 and 2 ng/ml plasma, respectively, for⁹⁰Zr and⁹⁶Zr. Zr plasma clearance and Zr response to a simple oral test were studied separately in different subjects by using the natural Zr solution. The data analysis was performed measuring the concentration of⁹⁰Zr to obtain indication on the time behavior and fractional level of Zr appearance in plasma depending on the administration routes. Two rabbits were intravenously injected 50 g⁹⁰Zr and a third rabbit was orally given 2.5 mg of⁹⁰Zr. Concentration in plasma samples of intravenously and orally given Zr isotopes are reported, as a function of time after administration. The injected tracer concentration relative to the first two rabbits were fitted simultaneously to obtain clearance parameters. Zr intestinal absorption is evaluated to be less than 0.2%. The work confirms that proton activation is a powerful tool for biokinetic studies with stable isotopes.     

Preparation of <Superscript>131</Superscript>I–betulinic acid and its biodistribution in murine model of hepatocellular tumor

The aim of this study was to examine the radioiodinating condition of betulinic acid and understand the possibility of ¹³¹I–betulinic acid (¹³¹I–BA) as a potential tumor radiotherapy agent through in vitro uptake and in vivo biodistribution studies ¹³¹I–BA was prepared by the reaction of betulinic acid with Na¹³¹I in the presence of hydrogen peroxide, and then purified by HPLC. The labeling yield was about 80%, and the radiochemical purity was greater than 95%. ¹³¹I–BA was found to be stable at 4 °C in saline containing 1% ethanol. In vitro studies showed that ¹³¹I–betulinic acid accumulated in the cancer cell lines (BEL-7402 and NCI-H446) in comparison with free ¹³¹I⁻. In vivo biodistribution study in KM mice bearing HepA tumor showed that ¹³¹I–BA stayed longer time in tumors than free ¹³¹I⁻. A significant differences were seen in tumor/muscle ratio at 4 h postinjection between ¹³¹I–BA and free ¹³¹I⁻. In vivo and in vitro studies showed the higher fraction of ¹³¹I–BA can be utilized for therapy and a higher dose will be delivered per targeting event. ¹³¹I–BA is a promising radiopharmaceutical in nuclear medicine, especially for hepatocellular tumor targeted radionuclide brachytherapy.