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1.
A first attempt to label insulin, a small protein with significant affinity to tumors with the α-emitter 211At was performed by an indirect method using N-succinimidyl 5-(tributylstannyl)-3-pyridinecarboxylate (SPC) as a bi-functional linker, and the stability of the conjugated insulin (211At-insulin) was evaluated in vitro and in vivo. SPC was synthesized by using 5-bromonicotinic acid as the starting material. With this bi-functional linker, insulin was conjugated with 211At in a labeling yield of 30–40%, with radiochemical purity of more than 98%. After 24 hours at room temperature, the radiochemical purity was still more than 95%, implying that 211At-insulin is fairly stable in vitro. Biodistribution of 211At-insulin was investigated in NIH strain mice. 211At accumulated rapidly in the liver post injection, with the maximum uptake of 4.29%I.D/g at 30 minutes, and was mainly excreted by kidney. More importantly, 211At-insulin uptake in some key organs or tissues, especially in thyriod, stomach, lung and spleen, was much less than that of free astatide (211At?). This result indicated that 211At-insulin has considerable stability in vivo as well as in vitro.  相似文献   

2.
With 2,3,5,6-tetrafluorophenyl 3-(nodo-carboranyl) propionate (TCP) as a new potential bi-functional linker, bovine serum albumin (BSA) was conjugated with 211At, and the conjugated model protein (211At-TCP-BSA) was preliminarily evaluated in vitro and in vivo by comparison with 211At-SAB-BSA and 211At-SAPC-BSA, which conjugated with 211At via aryl derivatives ATE (N-succinimidyl-3-(tri-n-butylstannyl) benzoate) or SPC (N-succinimidyl 5-(tributylstannyl)-3-pyridinecarboxylate). The radiolabeled intermediate 211At-TCP was coupled to BSA in yields ranging from 35 to 45% with radiochemical purity of more than 98%. The conjugated 211At-TCP-BSA exhibited considerable stability in vitro in 0.1 mol/L PBS (pH 7.6) at room temperature (RT), similar to 211At-SAPC-BSA and 211At-SAB-BSA. Biodistribution of the 211At conjugated protein was investigated in NIH strain mice by I.V injection. The results showed that 211At-TCP-BSA was constantly stable in vivo as well as in vitro, but more stable than 211At-SAPC-BSA and 211At-SAB-BSA. These results implied that radioastatinated carboranes based on B–At bonds are higher stability than radioastatinated aryl derivatives based on C–At to in vivo deastatination. In other word, TCP should be a promising bi-functional linker for 211At conjugation of proteins or antibodies.  相似文献   

3.
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>  相似文献   

4.
Metronidazole (MTNZ) is an antiprotozoa drug, could be labeled with the 99mTc. MTZL could be used as an ideal vehicle to deliver radioactive decay energy of 99mTc to the sites of tumor, thus facilitate tumor imaging. The process of labeling was done using tin chloride as reducing agent. The optimum conditions required to label 25 μg MTZL were 100 μg stannous chloride, 30 min reaction time, room temperature at pH 7–9 using 0.5 M phosphate buffer. The radiochemical purity of the labeled compound, at the above conditions, was determined using paper chromatography. The yield was about 93%. About 2.5 × l06 of Ehrlich Ascites Carcinoma (EAC) was injected intrapritoneally (i.p) to produce ascites and intramuscularly (i.m) in the right thigh to produce solid tumor in female mice. Biodistribution studies were carried out by injecting solution of 99mTc-MTZL in normal and tumor bearing mice. The uptake in ascites was over 5% of the injected dose per gram tissue body weight, at 4 h post injection and above 4% in solid tumor. These data revealed localization of the tracer in the tumor tissues with high percentage sufficient to use 99 mTc MTZL as promising tool for diagnosis of tumor.  相似文献   

5.
A novel electrochemical process to avail clinical grade 99mTc from (n,γ)99Mo has been demonstrated. The electrochemical parameters were optimized to maximize the 99mTc yield with minimal 99Mo contamination. 99Mo/99mTc generators containing up to 29.6 GBq (800 mCi) 99Mo were developed and their performance were extensively evaluated for 10 days without changing the operating conditions. Very high radioactive concentration of 99mTcO4 of acceptable quality, commensurate with hospital radiopharmacy requirements could be availed from the system with >90% yield. The compatibility of the product for the formulation of 99mTc labeled radiopharmaceuticals such as 99mTc-DMSA and 99mTc-EC was found to be satisfactory in terms of high labeling yields. The proposed route represents an important step for enhancing the scope of accessing clinical grade 99mTc from low specific activity (n, γ)99Mo.  相似文献   

6.
Improved radionuclide generator include a substantially insoluble salt of a radioactive parent which may be directly packed in column for subsequent elution of the daughter radionuclide. An improved 188Re generator was prepared by reacting a radioactive tungsten (188W) as parent radionuclide incorporated with aluminum chloride to obtain an insoluble radioactive aluminum tungstate matrix. The investigated matrix was characterized on the basis of the chemical composition, IR, thermal analysis and mechanical stabilities. The factors affecting the elution performance were studied such as influence of pH, molar ratio and drying temperature. From the obtained data, the molar ratio W:Al was 1.5:1 at pH = 4, the matrix dried at 105 °C for 2 h. Chromatographic and multichannel analysis has been currently used to investigate the radiochemical and radionuclidic purity respectively on eluted 188Re. An elution yield more than 80%, with radiochemical purity <98% and radionuclidic purity <99% with a 188W break through >10−4% of the column. The Al+3 and W contents value were about 2 and 3 μg/mL eluate. The obtained data approved the stability of the prepared generator and its suitability for medical application.  相似文献   

7.
In vivo imaging of tumours using radiolabelled somatostatin (SST) analogues has become an accepted clinical tool in oncology. HYNIC-Tyr3 octreotide and Tyr3 octreotide were synthesized by FMOC solid-phase peptide synthesis using a semi-automated synthesizer. These were analyzed and purified by RP-HPLC, mass spectroscopy, IR spectroscopy, 1H NMR and 13C NMR. The prochelator 6-BOC-HYNIC was also synthesised and characterised indigenously. HYNIC-Tyr3 octreotide was labelled with 99mTc using Tricine and EDDA as coligand by SnCl2 method. Labelling with 99mTc was performed at 100 °C for 15 min and radiochemical analysis by ITLC and HPLC methods. The radiochemical purity of the complex was over 98% and log p value was found to be −1.27 ± 0.12. The stability of radiolabelled peptide complex was checked at 37 °C up to 24 h. Blood clearance and protein-binding study was also performed. In vivo biodistribution studies in rat showed uptake of 99mTc-HYNIC-TOC in kidney than any other organs. The blood clearance was faster with rapid excretion through kidneys and relatively low uptake in liver.  相似文献   

8.
Radiocomplexation of fleroxacin (FXN) with technetium-99m and its characterization in terms of in vitro stability in saline and serum solutions, in vitro binding with live and heat-killed Escherichia coli, and biodistribution in male Wistar rats (MWR) artificially infected with live and heat-killed E. coli was studied. The 99mTc-FXN complex showed a radiochemical purity (RCP) yield of 98.10 ± 0.24% at 30 min using 125 μg of stannous fluoride, 74 MBq of sodium pertechnetate, and 2 mg of FXN. The complex was found to be more than 90% stable up to 4 h after constitution in normal saline. In serum, the emergence of 16.50% undesirable species was observed within 16 h of incubation at 37 °C. The 99mTc-FXN complex showed saturated in vitro binding with E. coli with a maximum value of 65.00% at 90 min. A fivefold increase in uptake of the complex was noted in the infected when compared with the inflamed and normal muscle of the MWR infected with live E. coli. The stable radiochemical profile in saline and serum, saturated in vitro binding with E. coli and increased uptake in the infected muscle, confirmed the potential of the 99mTc-FXN complex as an E. coli infection imaging agent.  相似文献   

9.
The majority of long-lived radionuclides produced in the nuclear fuel cycle can be regarded as “difficult-to-measure” nuclides, hence chemical separation is needed before the nuclear measurement of them. A combined radiochemical procedure that enables the simultaneous determination of some “difficult-to-measure” nuclides in medium and low level radioactive wastes has been developed in our laboratory. Recently, this method has been extended for determination of 237Np and 93Zr. 237Np and 93Zr are pre-concentrated by co-precipitation on iron(II) hydroxide and zirconium oxide, separated by extraction chromatography using UTEVA, and measured by inductively coupled plasma mass spectrometry (ICP-MS). As even traces of polyatomic ions and isotopes at m/z 237 or 93 cause considerable interferences during ICP-MS detection, a purification step by extraction chromatography was needed. Analyzing real samples (evaporation concentrates of a nuclear power plant) 66–99% and 31–99% chemical yields were achieved for Np and Zr, respectively.  相似文献   

10.
In homoaromatic systems, isotopic exchange (18F/19F) was previously (J Label Compd Radiopharm 18(12):1721–1730 [2], J Chem Soc Perkin Trans 1(3):295–298 [3]) proven to be advantageous, yet in general specific activity is thought to be low. For heteroaromatic systems, in particular, very few examples are published regarding the 18F-labelling of 2-substituted pyridines (J Label Compd Radiopharm 42:975–985 [9]). Therefore, in 2-fluoropyridines, we decided to study the 18F labelling by isotopic exchange (18F/19F). The radiochemical yield for 2-fluoropyridine was 90 ± 2%. Even if 2-fluoropyridine was substituted by an electron-donating group such as a methyl or a methoxy group, radiochemical yields were 80 ± 1 and 78 ± 1%, respectively. Although in benzenes, these substituents are known to decrease nucleophilic substitutions by 18F-Fluoride significantly. Moreover, by choosing appropriate concentrations of 2-fluoropyridines, reasonably high specific activities up to 10 GBq/μmol were obtained.  相似文献   

11.
Sitafloxacin dithocarbamate (SFDE) was synthesized, radiolabeled with technetium-99m (99mTc) using [99mTc-N]2+ core and evaluated its biological efficacy as a potential radiotracer for Staphylococcus aureus (S. aureus) infection in artificially infected rats (AIRT) and rabbits (AIRB). The radiochemical stability of the 99mTc labeled SFDE (99mTcN-SFDE) in saline and serum was determined by radio-HPLC and TLC methods, respectively. After, 1 min of reconstitution the value of radiochemical purity (RCP) was 99.00 ± 0.20% and was remained more than 90% unwavering even after 240 min of the radiolabeling. The 99mTcN-SFDE complex showed similar radiochemical permanence behavior in serum at 37 °C. The complex showed almost six fold higher specific in vitro binding with living than heat killed S. aureus. Biodistribution behavior was evaluated in S. aureus AIRT and whole body imaging (WBI) in AIRB, respectively. Seven fold up take was observed in infected muscle of the AIRT as compared to inflamed and normal muscles. The disappearance of activity from blood and appearance in urinary system indicated normal route of excretion of the complex. Scintigraphically, it was confirmed that the labeled SFDE was higher accumulated in the infected muscle higher than in inflamed and normal muscle. The high radiochemical stability in saline and serum, specific in vitro binding with S. aureus, precise in vivo distribution in S. aureus AIRT and targeted WBI in AIRB confirmed the possibility of the 99mTcN-SFDE complex as a potential and promising S. aureus infection radiotracer.  相似文献   

12.
The long-lived rare earth isotopes 151Sm (90 years, β max = 76.3 keV) and 147Pm (2.62 years, β max = 224.6 keV) are low-yield fission products that generally require lengthy separation procedures to isolate and count by their beta emissions. We will describe novel liquid scintillation counting techniques using radioactive tracers to determine radiochemical yields from an environmental matrix. The recovery of 151Sm is determined from the alpha decay (2.25 MeV) of 147Sm in the natural Sm carrier and is in excellent agreement with the gravimetric recovery. The 147Pm recovery is determined by the use of 145Pm (17.7 years, EC) tracer, custom-produced at LANL using an isotopically enriched target of 144Sm. We have determined the 145Pm recovery both from the 37.4 keV kα1 X-ray, and the electron-capture emissions by LSC. A comparison of these recovery methods is presented.  相似文献   

13.
A preparation of 125I-celecoxib is carried out via an electrophilic substitution reaction. The reaction parameters studied were celecoxib concentration, reaction temperature, pH of the reaction mixture and kinds of oxidizing agents in order to obtain a high radiochemical yield of the 125I-celecoxib. Using 3.7 MBq of Na125I, 150 μg (3.9 mM (mmol/L)) of celecoxib, and 1.6 mM (mmol/L) of chloramine-T (CAT) as oxidant at pH 4 and 60 °C for 15 min a maximum radiochemical yield of 125I-celecoxib (65%) was obtained. The labeled compound was separated and purified by means of high pressure liquid chromatography (HPLC). The biological distribution in infected mice indicates the suitability of radioiodinated celecoxib as imaging of tumor.  相似文献   

14.
2,2′-[(8-hydroxyquinolin-7-yl)methylazanediyl]diacetic acid (HQMADA) was synthesized via reaction of 8-hydroxyquinoline with iminodiacetic acid in presence of paraformaldehyde with a yield of 27%. The obtained compound was well characterized via different analytical techniques. Labeling of the synthesized compound with technetium-99m in pertechnetate form (99mTcO4 ) in the presence of stannous chloride dihydrate was carried out via chelation reaction. The reaction parameters that affect the labeling yield such as HQMADA concentration, stannous chloride dihydrate concentration, pH of the reaction mixture, and reaction time were studied to optimize the labeling conditions. Maximum radiochemical yield of 99mTc-HQMADA complex (91.9%) was obtained by using 1.5 mg HQMADA, 50 μg SnCl2·2H2O, pH 8 and 30 min reaction time. Biodistribution studies in mice were carried out in experimentally induced infection in the left thigh using E. coli. 99mTc-HQMADA complex showed higher uptake (T/NT = 5.5 ± 0.3) in the infectious lesion than the commercially available 99mTc-ciprofloxacin (T/NT = 3.8 ± 0.8). Biodistribution studies for 99mTc-HQMADA complex in Albino mice bearing septic and aseptic inflammation models showed that 99mTc-HQMADA complex able to differentiate between septic and aseptic inflammation.  相似文献   

15.
A practical and reliable HPLC method was used for the determination of 2-[4-N-(2-hydroxyethyl)-1-piperazinyl]-N′-ethanesulfonic acid (HEPES) content in the 68Ga-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-octreotide (DOTANOC). Linearity of this method was observed in a concentration range of 0.01–10 mg mL−1 and the quantitative limit (signal to noise = 11) was determined as 10 μg mL−1. The HEPES concentration in the final products of 68Ga-DOTANOC was typically lower than the detection limit. Pure water and HEPES buffer as reaction medium were investigated using various activities of gallium-68. It was demonstrated that the presence of HEPES buffer consistently furnished very high radiochemical purity of 68Ga-DOTANOC, which remained stable for several hours post-labeling. Evidence is provided that in addition to its role as a buffer, HEPES also functions as a radioprotectant agent.  相似文献   

16.
In the recent years interests on dihydropyrimidinone and their analogues have increased potentially due to their wide range of pharmacological/biological activities. Synthesis, radiolabeling with technetium-99 m (99mTc) and biological evaluation of 5-etoxycarbonyl-4-phenyl-6-methyl-3,4-dihydro-(1H)-pyrimidine-2-one (DHPM) were studied in this present work. After synthesis complexation of DHPM with 99mTc was carried out using stannous chloride as the reducing agent. The complex (99mTc-DHPM) was characterized by thin layer chromatography, radio-HPLC technique and determination of partition co-efficient. Radiochemical stability and particle size distribution of the complex were also measured. Biodistribution/scintigraphy studies were performed in rats and rabbits to evaluate the pharmacological characteristics of this complex. The radiochemical purity of the complex was over 95% as studied by thin layer chromatography and radio-HPLC. It was stable over 24 h at room temperature. Its partition coefficient indicated that it was a lipophilic complex. According to the European Pharmacopeia, >80% of 99mTc labeled radiopharmaceutical (99mTc-MAA) in the size range 10–50 μm, must be accumulated in the lungs 15 min after intravenous administration. In this study >85% of the 99mTc-DHPM complex in the average size of 40 μm. Biodistribution studies of 99mTc-DHPM in rat revealed that the complex accumulated in the lung with high uptake and good retention after intravenous administration. Scintigraphic studies in rabbit also revealed that most of the administered radiolabeled complex was accumulated in the lungs and after 1 h slowly excreted through the renal system. The lung uptake (ID%/g) was 10.12, 9.67, 8.60 and 5.01 and the lung/liver ratio was 7.49, 2.88, 2.62 and 1.87 at 2, 15, 30 and 60 min post-injection, respectively. These results suggested that 99mTc-DHPM could be suitable as a potential lung perfusion imaging agent. Further studies with 99mTc-DHPM and its derivatives are warranted to develop new 99mTc-labeled imaging agents for clinical applications.  相似文献   

17.
Rituximab was successively labeled with 177Lu-lutetium chloride. 177Lu chloride was obtained by thermal neutron flux (4 × 1013 n cm−2 s−1) of natural Lu2O3 sample with a specific activity of 2.6–3 GBq/mg. The macrocyclic bifunctional chelating agent, N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 °C using DOTA, N-hydroxy succinimide (NHS) in CH2Cl2. DOTA-rituximab was obtained by the addition of 1 mL of a rituximab pharmaceutical solution (5 mg/mL, in phosphate buffer, pH 7.8) to a glass tube pre-coated with DOTA-NHS (0.01–0.1 mg) at 25 °C with continuous mild stirring for 15 h. Radiolabeling was performed at 37 °C in 24 h. Radio-thin layer chromatography showed an overall radiochemical purity of >98% at optimized conditions (specific activity = 444 MBq/mg, labeling efficacy; 82%). The final isotonic 177Lu-DOTA-rituximab complex was checked by gel electrophoresis for structure integrity control. Radio-TLC was performed to ensure that only one species was present after filtration through a 0.22 μm filter. Preliminary biodistribution studies in normal rats were carried out to determine complex distribution of the radioimmunoconjugate up to 168 h. The biodistribution data were in accordance with other antiCD20 radioimmunoconjugates already reported.  相似文献   

18.
Pyrroloquinoline quinone (PQQ), an essential nutrient, antioxidant, redox modulator and nerve growth factor found in a class of enzymes called quinoproteins, was labeled with 99mTc by using stannous fluoride (SnF2) method. Radiolabeling qualification, quality control and characterization of 99mTc-PQQ and its biodistribution studies in mice were performed and discussed. Effects of pH values, temperature, time and reducing agents concentration on the radiolabeling yield were investigated. The quality control procedure of 99mTc-PQQ was determined by thin layer chromatography (TLC), radio high-performance liquid chromatography (RHPLC) and paper electrophoresis methods. The average radiolabeling yield was 94 ± 1% under optimum conditions of 0.99 mg of PQQ, 30 μg of SnF2, 0.5 mg of ethylenediaminetetraacetic acid disodium salt (EDTA-2Na) and 18.5 MBq of Na99mTcO4 at pH 6 and 25 °C with a response volume of 1 ± 0.1 mL. 99mTc-PQQ was stable and anionic. Lipid–water partition coefficient of 99mTc-PQQ was −1.49 ± 0.16. The pharmacokinetics parameters of 99mTc-PQQ were t 1/2α = 18.16 min, t 1/2β = 100.45 min, K 12 = 0.013 min−1, K 21 = 0.017 min−1, K e = 0.016 min−1, AUC (area under the curve) = 1040.78 ID% g−1 min and CL (plasma clearance) = 0.096 mL min−1. The dual-exponential equation was Y = 10.88e−0.038t  + 5.21e−0.0069t . The biodistribution of 99mTc-PQQ was studied in ICR (Institute for Cancer Research 7701 Burhelme Are., Fox Chase, Philadelphia, PA 1911 USA) mice. In vitro autoradiographic studies clearly showed that the 99mTc-PQQ radioactivity accumulated predominantly in the hippocampus and cortex, which had a high density of N-methyl-d-aspartate Receptor (NMDAR). The enrichment can be blocked by NMDAR redox modulatory site antagonists-ebselen (EB) and 99mTc-PQQ is therefore a promising candidate for the molecular imaging of NMDAR. To date, however, there have been no studies characterizing 99mTc-PQQ.  相似文献   

19.
In the present study, ytterbium-169 was produced via the 169Tm(p, n)169Yb nuclear process at the AMIRS (Cyclone-30, IBA, Belgium) cyclotron, irradiating Tm2O3 with proton particles of 15 MeV primary energy and 20 μA current for 20 min. Deposition of Tm2O3 on Cu substrate was carried out via by the sedimentation method. The 543 mg of thulium(III)oxide with 108 mg of ethyl cellulose and 8 mL of acetone were used to prepare a Tm2O3 layer of 11.69 cm2. Yields of about 0.643 MBq 169Yb per μAh were experimentally obtained. 169Yb was separated in 80 ± 5% radiochemical yield using liquid–liquid extraction. Solvent extraction of no-carrier-added 169Yb from irradiated thulium(III)oxide target hydrochloric solution was investigated using di-(2-ethylhexyl)phosphoric acid (HDEHP).  相似文献   

20.
To investigate the radio impurity in the radiolysis of 18F-FDG at high radiodose and radioconcentrated solutions and develop methods of repurification. The radiolysis of 18F-FDG was analyzed by TLC. The radio-impurity was confirmed by biodistribution and small animal PET/CT studies. 18F-FDG was unstable at high radioconcentrition over 37 GBq/mL or under basic condition. TLC, biodistribution and PET/CT all indicated that the main autoradiolysis byproduct was free fluoride ion. The radiolyzed 18F-FDG was repurified by solid-phase extraction (SPE) column. The repurified 18F-FDG had a radiochemical purity (RCP) of over 99% and significantly lower bone uptake than that was before repurification (P = 0.0003). There was a positive correlation between the recovery yield and the purity of 18F-FDG (R 2 = 0.66).  相似文献   

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