Os radiofármacos são preparações farmacêuticas com finalidade diagnóstica ou terapêutica que, quando prontas para o uso, contêm um ou mais radionuclídeos. São utilizados em Medicina Nuclear para diagnóstico e terapia de várias doenças. O tecnécio-99m-mercaptoacetiltriglicina (MAG3-99mTc) foi primeiramente preparado em 1986 na Universidade de Utah pelo Dr. Alan R. Fritzberg e tem sido utilizado para avaliação da filtração glomerular e dos túbulos renais. O objetivo deste trabalho foi definir as condições de preparação de uma formulação para obtenção de MAG3 na forma de um reagente liofilizado comercial, para ser marcado com 99mTc. Inicialmente foram preparados lotes teste baseados nas formulações europeia e americana, com pH final 6 e os resultados foram insatisfatórios. A mudança de pH para 12 resultou em aumento na pureza radioquímica, porém sem estabilidade de marcação com 99mTc em até 4 horas. O teste com a formulação cubana em pH 9,5 resultou em pureza radioquímica (% PRq) maior que 90% até 4 horas de marcação. O limite especificado para % PRq é de 90%. Com base nos resultados anteriores, foram definidos os componentes da formulação IPEN e três lotes do produto liofilizado com 100 frascos cada, foram avaliados quanto à estabilidade radioquímica e biológica até cerca de 9 meses. Quatro lotes piloto produzidos com 230 frascos liofilizados cada, estão em estudo de estabilidade até o presente momento. As atividades de marcação com 99mTc foram 0,74 - 3700 MBq (5 - 100 mCi), em 3 mL de NaCl 0,9%. A % PRq foi determinada em até 240 minutos de marcação utilizando cromatografia em camada delgada, com 2 sistemas diferentes: Metiletilcetona:acetato de etila 60:40 (v/v) em fita de iTLC-SG para determinação de 99mTcO4- em Rf = 1 e Acetonitrila:água 50:50 (v/v) em fita Whatman 3MM para determinação de 99mTcO2 em Rf = 0. Os resultados foram expressos como média % PRq ± desvio padrão considerando-se análises em duplicata de dois frascos para cada um dos tempos de marcação. 0,74 MBq (200 μCi) de atividade mínima ou 129,5 MBq (3500 μCi) de atividade máxima de marcação em 0,1 mL NaCl 0.9% foram administrados em camundongos Swiss e a radioatividade nos rins, fígado e vesícula, estômago, intestino e carcaça foi medida após 45 minutos. Os valores foram expressos como média % DI (Dose Injetada) ± DP. O estudo de toxicidade aguda foi realizado em um grupo de 10 camundongos machos da linhagem Balb/c, pesando entre 20-30 g, com cerca de dois meses de vida, por um período de 14 dias. Todos os resultados de controle de qualidade atenderam aos critérios especificados. Observou-se que o preparo e a adição dos reagentes, a quantidade de cloreto estanoso e o valor de pH nas etapas intermediárias foram fatores importantes na obtenção de um radiofármaco para marcação com 99mTc, como no caso do MAG3. / Radiopharmaceuticals are pharmaceutical preparations for diagnostic or therapeutic purposes that, when ready for use, contain one or more radionuclides. They are used in Nuclear Medicine for diagnosis and therapy of various diseases. Technetium-99m-mercaptoacetyltriglycine (99mTc-MAG3) was first prepared in 1986 at the University of Utah by Dr. Alan R. Fritzberg and has been used to assess glomerular filtration and renal tubules. The objective of this work was to define the preparation conditions of the formulation to obtain MAG3 in the form of a commercial lyophilized reagent to be labeled with 99mTc. Test lots were initially prepared based on the European and American formulations with final pH 6 and the results were unsatisfactory. The change in pH to 12 resulted in an increased radiochemical purity, however without 99mTc labeling stability in up to 4 hours. Testing with the Cuban formulation at pH 9.5 resulted in radiochemical purity (% PRq) greater than 90% up to 4 hours of labeling. The limit specified for % PRq is 90%. Based on the above results, the components of the IPEN formulation were defined and three batches of the lyophilized product with 100 vials each were evaluated for radiochemical and biological stability up to about 9 months. Four pilot batches produced with 230 freeze-dried vials each are currently in stability studies. The 99mTc labeling activities were 0.74 3,700 MBq (5 - 100 mCi) in 3 mL 0.9% NaCl. The % PRq was determined in up to 240 minutes of labeling using thin layer chromatography with 2 different systems: methyl ethyl ketone:ethyl acetate 60:40 (v/v) on iTLC-SG strip for determination of 99mTcO4- in Rf = 1 and acetonitrile:water 50:50 (v/v) on Whatman 3MM strip for determination of 99mTcO2 in Rf = 0. The results were expressed as mean % PRq ± Standard Deviation (SD) considering duplicate analyzes of two vials for each of the labeling times. 0.74 MBq (200 μCi) of minimal labeling activity or 129.5 MBq (3,500 μCi) of maximum labeling activity in 0.1 mL 0.9% NaCl were administered in Swiss mice and radioactivity in the kidneys, liver and gallbladder, stomach, intestine and carcass was measured after 45 minutes. Values were expressed as mean % ID (Injected Dose) ± SD. The acute toxicity study was performed on a group of 10 male Balb/c mice, weighing between 20-30 g with about two month old, for a period of 14 days. All quality control results met the specified criteria. It was found that the preparation and addition of the reactants, the amount of stannous chloride and the pH value in the intermediate steps were important factors in obtaining a radiopharmaceutical for labeling with 99mTc as in the case of MAG3.

Renogram in Nuclear Medicine is the main examination for the diagnosis of several diseases in children such as kidney failure or obstructive uropathy. The dosimetry of this examination is based on the group-specific values presented by the ICRP publications. The need for person-specific dosimetry in the Nuclear Medicine urged in the creation of a new image-based dosimetric method, based on the outcome of the examination of the renogram of each patient. With the help of an experimental procedure, the percentage of self-absorption inside the “source” organs and the absorption from the surrounding tissues of the transmitted radiation of the radiopharmaceutical (99m-Tc-MAG3) is calculated, leading with the use of the MIRD method, to the measurement of the activity of Technetium inside the patient’s organs during the renogram’s duration. Afterwards with the help of theoretical models, conclusions and assumptions the total cumulated activity of the patient’s organs is calculated. The results show similar values with other projects published, which were more invasive and less cost-effective for the department. / Στην πυρηνική ιατρική, τα νεφρογράμματα είναι η κύρια εξέταση για την διάγνωση ασθενειών στα παιδιά, όπως η νεφρική ανεπάρκεια και η ουροφρακτική ανεπάρκεια. Η δοσιμετρία αυτών των εξετάσεων στηρίζεται πάνω στα group-specific όρια του ICRP. Η ανάγκη για person-specific δοσιμετρία και στην Πυρηνική Ιατρική ώθησε στη δημιουργία μιας δοσιμετρικής μελέτης που στηρίζεται στην εικόνα (image-based) από το αποτέλεσμα της εξέτασης του νεφρογράμματος του κάθε ασθενή. Με τη βοήθεια μιας πειραματικής διάταξης υπολογίζεται το ποσοστό αυτο-απορρόφησης στα όργανα «στόχους» και το ποσοστό απορρόφησης της εκπεμπόμενης ακτινοβολίας από τους περιβάλλοντες ιστούς, οδηγώντας μαζί με την μέθοδο του MIRD, στον υπολογισμό της ενεργότητας του ραδιοφαρμάκου (99m-Tc-MAG3) μέσα στα όργανα του ασθενή καθ’ όλη την διάρκεια της εξέτασης. Με την βοήθεια θεωρητικών μοντέλων, συμπερασμάτων και υποθέσεων υπολογίζεται η συνολική ακτινική επιβάρυνση του ασθενούς και τα αποτελέσματα δίνουν παραπλήσιες τιμές με άλλες δημοσιευμένες εργασίες, που ακολούθησαν πιο επεμβατικές ή πιο κοστοβόρες για το τμήμα, μεθόδους.