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.     

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.     

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>     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Rapid and subnanomolar assay of recombinant human erythropoietin by capillary electrophoresis using NanoOrange precolumn labeling and laser‐induced fluorescence detection

Because of less functionally critical carbohydrate sectors that contributed to the stability, efforts have been made to quantify intact recombinant human erythropoietin. A simple, rapid capillary electrophoresis with laser‐induced fluorescence method for the assay of recombinant human erythropoietin was developed, with a limit of detection of intact recombinant human erythropoietin at subnanomolar concentration (up to 10 ng/mL or 3 × 10^?10 M), which is among the lowest reported. High sensitivity was accomplished by precolumn derivatization with the noncovalent dye NanoOrange. Capillary electrophoresis separation and reaction conditions were carefully manipulated for avoiding microheterogeneity of glycoforms and inhomogeneity of multiple labeling products. The fluorescence signal was linear over the range of 10 ng/mL–10 μg/mL, corresponding to the detection requirement of recombinant human erythropoietin in biofluids and pharmaceutical samples, as demonstrated by a real sample analysis. Although the salt in reaction mixtures showed a detrimental effect on the fluorescence of the derivatives, this method could tolerate a certain amount of salt, extending its application in biofluid analysis. In addition, zero‐order fluorescence emission kinetics was obtained, indicating that the rapid decay of recombinant human erythropoietin was derived from a self‐quenching effect.     

Preparation of Iodine-131 Labeled Hippuran by Exchange Method

I^131?labeled Hippuran was prepared by isotopic exchange reaction between ortho-iodohippuric acid and I¹³¹-iodide. Special emphasis was placed on the separation of I^131?labeled Hippuran and its analysis with respect to the radiochemical purity. It was found that the prepared I¹³¹-labeled Hippuran meets the requirement as the radiopharmaceutical to be used for medical purpose.     

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.     

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.     

Radiolabeling of EGCG with 125I and its biodistribution in mice

The aim of the present study was to label EGCG with ¹²⁵I and to determine its radiopharmaceutical potential in mice. EGCG was labeled with ¹²⁵I using the iodogen method. The labeling yield and the radiochemical purity of ¹²⁵I–EGCG were determined by radio thin-layer chromatography (RTLC). The Labeling yield was approximately 89.4 %. The radiochemical purity was approximately 96.4 %. The biodistribution studies of the labeled compound (specific activity; 0.47 TBq/μg) were performed in male Kunming mice. The uptakes of ¹²⁵I–EGCG in some organs were determined at different time after injection to the mice. 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. Incorporation of radioactivity in the various tissue/organ was confirmed by microautoradiography. ¹²⁵I–EGCG uptake in the stomach and salivary gland was higher than other organ/tissue. The black silver grains was concentrated in the nucleus, cytoplasm, intercellular substance and capillaries of that various organs, and its unevenly distributed. Thus, ¹²⁵I–EGCG may be radiopharmaceutical for the imaging of the stomach and salivary gland.     

Preparation, quality control and stability of 131I-Lanreotide

Summary Lanreotide, a synthetic octapeptide analog of a native hormone somatostatin, was labeled with ¹³¹I, the most widely used therapeutic and easily available radionuclide. Radioiodination of Lanreotide was carried out by Chloramine-T and Iodogen methods. Chloramine-T and Iodogen were used as oxidizing agents to form an electrophilic iodine species, which then labeled the tyrosine of Lanreotide. The maximum radiolabeling yield was ~80%. Chloramine-T was found more suitable than the Iodogen method, because nearly 25% of the initial iodine activity was lost/adsorbed on the Iodogen coating. Thin layer and high performance liquid chromatographies were used for monitoring the reaction of ¹³¹I with Lanreotide, the stability and purity of ¹³¹I-Lanreotide.     

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.