NATANAEL GOMES DA SILVA

NATANAEL GOMES DA SILVA

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Proposal of an identification test for MIBI-TEC® lyophilized reagent using infrared spectroscopy
2019 - SANTOS, JOEL M. dos; FUKUMORI, NEUZA T.O.; OLIVEIRA, IDELI M. de; MARTINS, PATRICIA de A.; SILVA, NATANAEL G. da; MATSUDA, MARGARETH M.N.
Quality Control is part of the Good Manufacturing Practices (GMP) responsible for the evaluation and release of pharmaceutical components, including active ingredients and excipients, to assure compliance with the specifications in pharmacopoeias. GMP for radiopharmaceuticals is regulated by RDC N. 17/2010 and RDC N. 63/2009 (ANVISA) establishing the minimum quality standards in industrial manufacture. Pharmacopoeias have the specifications for lyophilized reagents (LR) labeled with 99mTc regarding radiochemical purity, biodistribution and, in case of parenteral use, bacterial endotoxins and sterility tests must be performed. In radiopharmaceutical monographs, the necessity of non radioactivity assays for releasing lyophilized reagents are not well described, but ANVISA requires assays to assure the quality of the lyophilized powder, as active ingredient quantification and identification assays, stannous ion quantification and moisture determination. Infrared (IR) spectroscopy is widely used for identification of substances, mainly raw materials. The aim of this work is to propose an identification assay for MIBI-TEC® LR powder using IR spectroscopy. MIBI-TEC® batches were produced at IPEN/CNEN-SP and about 2 mg of the LR powder were mixed with 200 mg KBr, pressed at 80 kgf during 5 minutes into the holder to obtain a transparent pellet. The pellet was placed in ABB IR spectrometer, FTLA 2000 model, and a spectrum in the medium infrared region of 450 to 4000 cm-1 was acquired using Grams software. Tetramibi cuprous tetrafluoroborate, stannous chloride dihydrate, cysteine hydrochloride monohydrate, sodium citrate and mannitol had their respective IR spectrum recorded and the main characteristic absorptions were established for each formulation component. In the MIBI-TEC® spectrum, it was possible to observe a well characterized absorption in 2193 cm-1 which represents the presence of C≡N binding of tetramibi cuprous tetrafluoroborate active ingredient, free of interference, indicating that IR spectrum can be used as identification assay of the LR.
Dose calibrator and gamma counter
2019 - SILVA, VITOR M.A. da; SOUSA, JURANDIR A. de; MARTINS, PATRICIA de A.; FUKUMORI, NEUZA T.O.; SILVA, NATANAEL G. da; MATSUDA, MARGARETH M.N.
To ensure that pharmaceutical products have and maintain the structure, identity, purity, concentration, potency and safety characteristics required for their use, there is a set of standard procedures called Good Manufacturing Practices (GMP). In Brazil, the National Sanitary Surveillance Agency (ANVISA) regulates the GMP production of medicines through RDC17/2010 and for radiopharmaceuticals through RDC 63/2009 and 38/2008, to ensure their safe and correct use in commercial production and nuclear medicine services, respectively. Most 99mTc radiopharmaceutical monographs have biological distribution specifications. Using invasive method, 99mTcradiopharmaceuticalsare assessed by the injection into animals of defined strains and the radioactivity (as percentage of retainedor injected dose -%RDor%ID)ismeasured in specified organs. Technetium-99m Sestamibi radiopharmaceutical (99mTc-2-methoxy-isobutyl-isonitrile; 99mTc-sestamibi; MIBI-TEC®) monograph is related in USP 41, but the biological distribution assay is not included. At IPEN, the biodistribution test is performed as established in the Radiopharmaceutical Quality Control Manual of ARCAL XV (1999) - International Atomic Energy Agency (IAEA), for each batch. The objective of this work is to compare MIBI-TEC®biodistribution results using dose calibrator and gamma counter with sodium iodide detector by measuring the radioactivity in the organs. Three batches of MIBI-TEC®were used and 1 vial of lyophilized reagent (LR) was labeled with 5-10 mCiin 1-3 mL of 99mTc eluate. 200-300 μCi in 0.2 mLwereinjected in 3 Balb-Cmice. After 30 minutes of biodistribution, heart, lung, muscle, liver, paw, column and tail were withdrawn, weighed and radioactivity was measured in dose calibrator and gamma counter (μCi andcpm, respectively). %ID/g ratio in the organs of interest was calculated using the data obtained by both equipment and the results were compared. No significant differences were observed and it was possible to conclude that either a dose calibrator or a gamma counter can be used in the routine of quality control.
Radiochemical purity determination of technetium (99m)Tc-sestamibi by high performance liquid chromatography (HPLC)
2019 - MARTINS, PATRICIA de A.; FUKUMORI, NEUZA T.O.; SILVA, NATANAEL G. da; MATSUDA, MARGARETH M.N.
The assessment of the extent of reversible or irreversible mitochondrial damage after myocardial ischemia is performed by obtaining myocardial perfusion SPECT-CT images of Technetium-99m Sestamibi radiopharmaceutical (99mTc-2-methoxy-isobutyl-isonitrile; 99mTc-sestamibi; 99mTc-MIBI). For quality control purposes, the monograph of the United States Pharmacopoeia (USP) was followed. The determination of the radiochemical purity of 99mTc-sestamibi involves the use of two chromatographic methods: thin layer chromatography in reverse phase and high performance liquid chromatography. This work aims to determine the radiochemical purity of 99mTc-sestamibi by the HPLC method described in USP. The analyses were performed on a Shimadzu liquid chromatography, LC-20AT model, consisting of two pumps, degasser, automatic sample injector, UV-visible detector and Bioscan radioactivity detector. The column used was μBondapack C18 (3.9 x 300 mm, 10 μm, Waters) and the mobile phase was a mixture of acetonitrile, 0.05 mol L-1 ammonium sulfate and methanol (20:35:45). 5 μL of sample (approximately 250 μCi) was injected with a 2 mL min-1 mobile phase flow. According to the USP monograph, the retention time for 99mTc-sestamibi is 5-10 minutes and for the 99mTc-pentamibidimethylvinylisonitrile impurity is 6-13 minutes. Not less than 90% of the total radioactivity must be present as 99mTc-sestamibi and not more than 5% as 99mTc-pentamibidimethylvinylisonitrile. For 12 analyzed batches of MIBI-TEC® produced at IPEN/CNEN-SP, the product presented a retention time of 7 minutes and the 99mTc-pentamibidimethylvinylisonitrile impurity formation was not observed.
Study of 99mTc-DMSA biodistribution in experimental animals
2017 - CASTRO, THAIS O.M. de; SILVA, NATANAEL G. da; COLTURATO, MARIA T.; FELGUEIRAS, CARLOS F.; MENGATTI, JAIR; FUKUMORI, NEUZA T.O.; MATSUDA, MARGARETH M.N.; ARAUJO, ELAINE B. de
99mTc-DMSA, succimer (99m Tc), is a radiopharmaceutical commonly used in nuclear medicine for renal function evaluation by imaging. In order to achieve adequate labeling of the product with good radiochemical yield and standardized biological distribution, the interval of 185 - 3700 MBq should be kept in a maximum volume of 3 mL for product labeling. Moreover, one should avoid exposing the reconstituted solution to oxygen and using the product after four hours post labeling. The aim of the study was to quantify and evaluate the influence of different DMSA complexes on biological distribution of the radiopharmaceutical in experimental animals, taking in account variations in the labeling parameters. Radiochemical purity was determined by paper and thin layer chromatography using both acetone/Whatman 3MM, 0.9% NaCl/TLC-SG and npropanol/ H2O/acetic acid (4:3:1 V/V/V)/TLC-SG systems respectively for quantification of 99mTcO4 - and 99mTcO2 plus some 99mTc-DMSA complexes. The labeling activity did not significantly affect the extent of the main complex generation. The presence of oxygen and the concentration of 99Tc did not markedly change the percentage of the radiochemical impurities in the preparation. Radiochemical purity tests of the DMSA-99mTc based on IPEN-CNEN DMSA-TEC reagent and on another producer’s reagent showed similar results. Although the routine method used by IPEN-CNEN to determine the radiochemical yield of 99mTc-DMSA was not able to discriminate among 99mTc-DMSA complexes, the renal uptake and the kidney to liver plus spleen uptake ratio in rats met the official compendia criteria for the radiopharmaceutical.
Metodo cintilografico nao invasivo para estudo de biodistribuicao de radiofarmacos
2010 - ALMEIDA, ERIKA V.; SILVA, NATANAEL G.; FREIRE, ANTONIO C.; MONTEIRO, ELISIANE de G.; BENEDETTI, STELLA; MURAMOTO, EMIKO; FUKUMORI, NEUZA T.O.; MATSUDA, MARGARETH M.N.; VASCONCELLOS, MARINA B.A.
Acute and subacute toxicity of sup(18)F-FDG
2013 - DANTAS, DANIELLE M.; SILVA, NATANAEL G. da; MANETTA, ANA P.; OSSO JUNIOR, JOAO A.
Controle de qualidade e EC-sup(99m)Tc: determinacao de pureza radioquimica e investigacao da influencia de impurezas na biodistribuicao
2009 - ALMEIDA, ERIKA V.; MONTEIRO, ELISIANE G.; ALVES, EDSON V.; SILVA, NATANAEL G. da; FUKUMORI, NEUZA T.O.; BARBOZA, MARYCEL F. de; MENGATTI, JAIR; MATSUDA, MARGARETH M.N.; VASCONCELLOS, MARINA B.A.
Biological profile of sup(99m)TcHYNIC-betaAlA-NT (8-13) in MDA MB-231 breast cancer cell line
2009 - TEODORO, RODRIGO; FAINTUCH, BLUMA L.; WIECEK, DANIELLE P.; SILVA, NATANAEL G.; VALLEJO, NATALIA M.
Urethane influence in the urine formation in swiss rats and syrian hamster
2011 - LIMA, MARINA F.; SILVA, NATANAEL G.; MESQUITA, CARLOS H. de
Identification, control and quantification of residual sol vents in radiopharmaceutical preparations
2009 - MARTINS, PATRICIA de A.; SILVA, JOSE L.; RAMOS, MARCELO P.S.; OLIVEIRA, IDELI M.; SILVA, NATANAEL G.; FUKUMORI, NEUZA T.O.; MATSUDA, MARGARETH M.N.