Influence of radiation on endotoxin test using the PTS TM for 18-FDG radiopharmaceutical

O FDG-18 é o radiofármaco mais utilizado nos exames de PET e PET CT. O FDA recentemente aprovou o uso do PTS TM (Portable Test System) como método alternativo ao teste padrão de endotoxina, proposto pela Farmacopéia Americana, considerando que no primeiro há um tempo de espera de 1 hora frente a somente 15 minutos do segundo. Estudo recentes demonstram que a radiação poderia interferir no teste do PTS TM. De modo a avaliar os efeitos da radiação no teste PTS TM foram analisados 27 lotes de F-18 FDG produzidos no Instituto de Engenharia Nuclear. Os resultados demonstraram que em todos os casos nenhuma correlação direta com a radiação foi observada.F-18 FDG (2-[18-F] fluoro-2-deoxy-D-glucose) is the most frequently used radiopharmaceutical for PET and PET CT imaging exams. The FDA recently approved the use of the PTS TM (Portable Test System) as an alternative to the standard test proposed by the United States Pharmacopeia using the LAL (Limulus Amebocyte Lysates), that takes longer to perform (about 1h) than the PTS TM (15 min). Recent studies have demonstrated that radiation could interfere with the PTS TM test. In order to study the effects of radiation on the PTS TM test and/or equipment, 27 batches of F-18 FDG produced in the Nuclear Engineering Institute were analyzed. The results showed that no direct correlation with radiation was found in any of the cases

Guidance for nuclear medicine staff on radiopharmaceuticals drug interaction

Numerous drug interactions related to radiopharmaceuticals take place every day in hospitals many of which are not reported or detected. Information concerning this kind of reaction is not abundant, and nuclear medicine staff are usually overwhelmed by this information. To better understand this type of reaction, and to help nuclear medicine staff deal with it, a review of the literature was conducted. The results show that almost all of radiopharmaceuticals marketed around the world present drug interactions with a large variety of compounds. This suggests that a logical framework to make decisions based on reviews incorporating adverse reactions must be created. The review also showed that researchers undertaking a review of literature, or even a systematic review that incorporates drug interactions, must understand the rationale for the suggested methods and be able to implement them in their review. Additionally, a global effort should be made to report as many cases of drug interaction with radiopharmaceuticals as possible. With this, a complete picture of drug interactions with radiopharmaceuticals can be drawn.Diversos casos de interações medicamentosas com radiofármacos ocorrem diariamente na rotina hospitalar, contudo muitos deles não são notificados ou mesmo percebidos. Informações a respeito desse tipo de reação não é abundante e os profissionais da medicina nuclear muitas vezes estão assoberbados por essas informações. De modo a entender esse tipo de reação e auxiliar a medicina nuclear a lidar com essa situação uma revisão da literatura foi realizada. Os resultados mostraram que a totalidade dos radiofármacos comercializados no mundo apresentam interação medicamentosa com uma enorme variedade de outros medicamentos. Dessa forma sugere-se que revisões sobre radiofármacos inclua um capítulo sobre efeitos adversos. Além disso, um esforço mundial para notificar efeitos adversos deve ser realizado, pois somente dessa forma se terá um quadro real da situação referente interações medicamentosas com radiofármacos

Are radiopharmaceuticals safe? the case of FDG-18

5 p.Too many false-positive and adverse reactions related to radiopharmaceuticals take place every day in hospitals routine, but many are not reported or even sensed. Information concerning these kind of reactions is not abundant and nuclear medicine staff is usually overwhelmed by this information. As every healthcare intervention carries some risk of harm, clinical decision making needs to be supported by a systematic assessment of the balance of benefit to harm. A systematic review that considers only the favorable outcomes of an intervention, without also assessing the adverse effects and false positives reactions, can mislead by introducing a bias favoring the intervention that in the case o radiopharmaceuticals may to render a important factor related not even to the quality of the drug but even to the quality of the diagnosis. The results suggest a logical framework to make decisions in reviews that incorporate false positive and adverse reactions. Also, was explored situations where a comprehensive investigation of false positive reactions and adverse effects was warranted and suggest strategies to identify practicable and clinically useful outcomes. We concluded that there is the necessity to include and to recognize how strategic choices made in the review process determine what harms are found, and how the findings may affect clinical decisions. Researchers undertaking a systematic review that incorporates false positive reaction and adverse reactions must understand the rationale for the suggested methods and be able to implement them in their review. Beyond a world effort should be made to report as many cases of false positive and adverse reactions with radiopharmaceuticals as possible. Only if this is done a complete picture of false positive reactions with radiopharmaceuticals can be drawn

Development and validation of UV/VIS spectroscopy method for determination of atezolizumab in pharmaceutical products

Aim: The aim of this study was to develop and validate a simple, fast, and reliable UV visible methodology for the determination of atezolizumab in pharmaceutical products. Methods: The maximum wavelength of atezolizumab was determined using a UV/Vis spectrum and the calibration curve has been established. Validation studies were carried out to determine the reliability of the spectrophotometer method used in quantification of pharmaceutical products. Results: According to the experimental data, the developed method was linear in a range varying from 0.10 to 1.50 mg.mL-1 determined by 6 individuals calibrations points. The r2 value was 0.9995 indicating a 99.95% correlation in linearity and precision. The robustness showed good and similar values and the limit of detection and limit of quantification were 0.005 mg.mL-1 and 0.018 mg.mL-1, respectively. Conclusion: The data corroborates the reliability as applicability of the developed UV/Vis spectroscopy method for quantitatively determining the amount of atezolizumab in pharmaceutical products

Linearity evaluation of analytical methods of radiopharmaceutical fluorodeoxyglucose-18

Radiofármacos são medicamentos utilizados na Medicina Nuclear para avaliar funções biológicas e patofisiológicas, realizar estudos do funcionamento do cérebro e diversas outras enfermidades, assim comodesenvolver uma terapia eficaz. Tomografia por emissão de pósitron e tomografia computadorizada por emissão de fóton único são alguns dos métodos que utilizam radiofármacos. Desenvolvimento de novos radiofármacos é a solução para a análise in vivo de imagens endógenas. Contudo não só o desenvolvimento é importante. A qualidade e o comportamento do radiofármaco desenvolvido devem ser comprovadas , diariamente. Nesse trabalho os autores avaliam a metodologia de determinação de etanol e do teor de F-18 e FDG-18 como forma de avaliação da qualidade do produto final, e dos método utilizados, assim como dos equipamentos. Os resultados revelam que a metodologia de determinação de etanol em solução de FDG-18 deve ser revista. Contudo a análise de teor de F-18 e FDG-18, mostrou-se bastante eficaz.Radiopharmaceuticals are drugs used in Nuclear Medicine to measure physiological and biological functions, to evaluate higher brain function, to study the pathophysiology of various disorders and to develop effective therapy. Positron emission tomography (PET) and single-photon emission computed tomography are representative molecular imaging methods. Development of radiopharmaceuticals is a key for successful in vivo imaging. However, not only the development of new radiopharmaceuticals are important. The quality and behavior of this radiopharmaceuticals must be improved daily. In this manuscript, the authors introduces experiences and concepts for development of quality control test to be used in the routine of radiopharmaceuticals industry, in order to verify the quality of the method and the quality of the final product (radiopharmaceuticals) produced. The results showed that an alternative methods for quantification of ethanol is required. Despite of the results of the linearity, the quantification of content of radiopharmaceuticals (F-18 and FDG-18) shown to be satisfactory.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Obligations, precautions and pending issues in regulatory development for radiopharmaceuticals in Brazil

Radiopharmaceuticals are compounds that have a radionuclide and may be gamma-radiation emitter (γ) or positrons emitter (β+), linked to a molecule with specific diagnostic and therapeutic purposes. The progress in the use of radiopharmaceuticals has culminated to a sector in common with other types of drugs: regulation and surveillance. From 2006 on, production, marketing and use of these drugs were open to the Brazilian market granting much more freedom due to the Constitutional Amendment 49, resulting from the previous Constitutional Amendment 199/03 which removes the Union monopoly for this kind of manipulation and granted this production to other nuclear medicine. From this date on, the amount of this type of sold product have been greatly increased, and the nucleus of surveillance and regulation in Brazil have also advanced in the legislative processes, creating documents that are now more focused on radiopharmaceuticals in the national territory (Resolutions No. 63 and No. 64). In international overview, there is too much to be done in regulatory terms in Brazil, such as adding mainly issues of drugs surveillance to pharmacovigilance practice in radiopharmaceuticals drugs.Radiofármacos são compostos que possuem um radionucleotídeo, podendo ser emissor de radiação gama (γ) ou emissor de pósitrons (β+), ligado a uma molécula específica com finalidade diagnóstica e terapêutica. O avanço no uso dos radiofármacos tem culminado a um setor em comum com outros tipos de medicamentos: a regulamentação e fiscalização. Após 2006, a produção, a comercialização e a utilização destes medicamentos foram abertas ao mercado interno brasileiro com maior liberdade, pois a Emenda Constitucional 49, vinda da Emenda Constitucional 199/03, que retira da União o monopólio deste tipo de manipulação, ofereceu a outros centros de medicina nuclear a oportunidade desta produção. A partir desta data, a quantidade comercializada deste tipo de medicamento aumentou absurdamente e os núcleos de vigilância e regulamentação do Brasil avançaram também nos processos legislativos, criando os documentos mais voltados a Radiofármacos existentes no território nacional, as Resoluções n° 63 e n° 64. Em visão internacional, há muito ainda a ser feito em termos regulatórios no Brasil somando principalmente os assuntos vigilantes dos medicamentos como a prática de Farmacovigilância em Radiofármacos

Indirect calculation of monoclonal antibodies in nanoparticles using the radiolabeling process with technetium 99 metastable as primary factor: Alternative methodology for the entrapment efficiency

[EN] The use of monoclonal antibodies (Mab) in the current medicine is increasing. Antibody-drug conjugates (ADCs) represents an increasingly and important modality for treating several types of cancer. In this area, the use of Mab associated with nanoparticles is a valuable strategy. However, the methodology used to calculate the Mab entrapment, efficiency and content is extremely expensive. In this study we developed and tested a novel very simple one-step methodology to calculate monoclonal antibody entrapment in mesoporous silica (with magnetic core) nanoparticles using the radiolabeling process as primary methodology. The magnetic core mesoporous silica were successfully developed and characterised. The PXRD analysis at high angles confirmed the presence of magnetic cores in the structures and transmission electron microscopy allowed to determine structures size (58.9 +/- 8.1 nm). From the isotherm curve, a specific surface area of 872 m(2)/g was estimated along with a pore volume of 0.85 crn(3)/g and an average pore diameter of 3.15 nm. The radiolabeling process to proceed the indirect determination were well-done. Trastuzumab were successfully labeled (>97%) with Tc-99m generating a clear suspension. Besides, almost all the Tc-99m used (labeling the trastuzumab) remained trapped in the surface of the mesoporous silica for a period as long as 8 h. The indirect methodology demonstrated a high entrapment in magnetic core mesoporous silica surface of Tc-99m-traztuzumab. The results confirmed the potential use from the indirect entrapment efficiency methodology using the radiolabeling process, as a one-step, easy and cheap methodology. (C) 2018 Elsevier B.V. All rights reserved.The authors would like to thank the National Scientific and Technological Research Council (CNPQ) and the Rio de Janeiro State Research Foundation (FAPERJ) for funding. Authors also gratefully acknowledge the financial support from the Ministerio de Economia y Competitividad (Project MAT2012-38429-004-01) and the Generalitat Valenciana (project PROMETEO/2009/016) for support.Helal-Neto, E.; Sánchez-Cabezas, S.; Sancenón Galarza, F.; Martínez-Máñez, R.; Santos-Oliveira, R. (2018). Indirect calculation of monoclonal antibodies in nanoparticles using the radiolabeling process with technetium 99 metastable as primary factor: Alternative methodology for the entrapment efficiency. Journal of Pharmaceutical and Biomedical Analysis. 153:90-94. https://doi.org/10.1016/j.jpba.2018.02.017S909415

Radiopharmacy history and implications of amendment 49

O objetivo deste artigo é descrever a história dos radiofármacos e as implicações da Emenda Constitucional N. 49 sobre a produção de radiofármacos no Brasil.The purpose of this paper is to describe the history of radiopharmaceutical and the implications of amendment 49 upon the radiopharmaceuticals production in Brazil

Quality control of radiopharmaceutical 99mTc-MAG3

The use of mercaptoacetyltriglycine (MAG3) as a radiopharmaceutical is well known. The MAG3 is formerly called Technetium-99m (99mTc) mercaptoacetyltriglycine and it is the standard radiopharmaceuticals for renal scintilography . In this study we propose three methodologies based on the use of a new stationary phase (paper Hahnemuhle) and a mobile phase. The results showed that all the three conditions were very close, and for this reason can be interchangeable.Colegio de Farmacéuticos de la Provincia de Buenos Aire