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A grande aplicação dos radiofármacos está em medicina nuclear diagnóstica representando 95% dos procedimentos realizados, porém, nos últimos anos, tem crescido consideravelmente a sua aplicação em procedimentos terapêuticos. Os radionuclídeos que emitem particulas ionizantes (α, β e elétrons Auger) são indicados para tratamento de tumores. Tumores malignos são responsáveis por aproximadamente 12% dos óbitos e representam a terceira causa de mortalidade no Brasil. O 188Re é um dos mais atrativos radioisótopos para uma variedade de aplicações terapêuticas em medicina nuclear, oncologia e intervenções cardiológicas, é totalmente favorável e conveniente pelo fato de que ele é livre de carregador e pode ser obtido de forma econômica na forma de um gerador de 188W/188Re, além de possuir uma meia-vida fisica de 16,9 horas e 100% de emissão de radiação β-. A partir da década de 2000 vêm sendo realizadas diversas investigações envolvendo marcações de moléculas com 188Re. Os tumores metastáticos são a forma mais comum de malignidade esquelética. Em casos metastáticos os principais objetivos do tratamento são a prevenção de fraturas patológicas e promover a sobrevida com o máximo de preservação de função permitindo que o paciente mantenha o máximo possível de mobilidade e controle da dor. O objetivo deste trabalho foi realizar a comparação das marcações de diversos fosfonatos (Metileno disfofonato de Sódio MDP, Ácido Etilenodiaminotetrametilenofosfônico EDTMP, e do diclorometilenobifosfonato de sódio - Clodronato) com 188Re para terapia de metastáses ósseas. Fosfonatos são inibidores da reabsorção óssea osteoclástica e são efetivos neste tratamento. As marcações do MDP, EDTMP e Clodronato com 188Re foram otimizadas utilizando como agente redutor o cloreto estanoso (SnCl2 2H2O) e como agente estabilizante o ácido ascórbico. As variáveis estudadas foram massa do ligante, massa do SnCl2.2H2O, massa do ácido ascórbico, tempo, pH e temperatura da reação. Os resultados mostraram que se obteve um excelente rendimento de marcação de 98% para o 188Re-MDP, de 83% para o 188Re-EDTMP e 85% para o 188Re-Clodronato. / The wide application of radiopharmaceuticals in nuclear medicine, representing 95% of procedures performed is in diagnosis, but in recent years, its application in therapeutic procedures has grown considerably. The radionuclides that emit ionizing particles (α, β, and Auger electrons) are indicated for the treatment of tumors. Malignant tumors account for approximately 12% of deaths and represent the third cause of mortality in Brazil. 188Re is one of the most attractive radioisotopes for a variety of therapeutic applications in nuclear medicine, oncology and cardiology interventions, is fully favorable and convenient because it is carrier free and can be obtained inexpensively in the form of a generator of 188W/188Re, and has a physical half-life of 16.9 hours and 100% of β-radiation emission. From the 2000s several investigations have been conducted involving molecules labeled with 188Re. Metastatic tumors are the most common form of malignancy in the skeleton. In metastatic cases the main goals of treatment are the prevention of pathological fractures and the promotion of survival with maximum preservation of function allowing the patient to maintain the greatest possible mobility and pain control. The objective of this study was to compare the labeling of various phosphonates (Sodium methylene diphosphonate - MDP, Ethylenediaminetetramethylene phosphonic acid - EDTMP, and sodium dichloromethylenediphosphonate - clodronate) with 188Re for bone metastases therapy. Phosphonates are inhibitors of osteoclastic bone resorption and are effective in treatment. The labeling of MDP, EDTMP and Clodronate with 188Re was optimized using stannous chloride (SnCl2·2H2O) as reducing agent, and ascorbic acid as stabilizing agent. The variables studied were the ligand mass, SnCl2.2H2O mass, mass of ascorbic acid, time, pH and temperature of the reaction. The results showed an excellent labeling yield of 98% for 188Re-MDP, 83% for 188Re-EDTMP and 85% for 188Re-Clodronate.

A grande aplicação dos radiofármacos está em medicina nuclear diagnóstica representando 95% dos procedimentos realizados, porém, nos últimos anos, tem crescido consideravelmente a sua aplicação em procedimentos terapêuticos. Os radionuclídeos que emitem particulas ionizantes (α, β e elétrons Auger) são indicados para tratamento de tumores. Tumores malignos são responsáveis por aproximadamente 12% dos óbitos e representam a terceira causa de mortalidade no Brasil. O 188Re é um dos mais atrativos radioisótopos para uma variedade de aplicações terapêuticas em medicina nuclear, oncologia e intervenções cardiológicas, é totalmente favorável e conveniente pelo fato de que ele é livre de carregador e pode ser obtido de forma econômica na forma de um gerador de 188W/188Re, além de possuir uma meia-vida fisica de 16,9 horas e 100% de emissão de radiação β-. A partir da década de 2000 vêm sendo realizadas diversas investigações envolvendo marcações de moléculas com 188Re. Os tumores metastáticos são a forma mais comum de malignidade esquelética. Em casos metastáticos os principais objetivos do tratamento são a prevenção de fraturas patológicas e promover a sobrevida com o máximo de preservação de função permitindo que o paciente mantenha o máximo possível de mobilidade e controle da dor. O objetivo deste trabalho foi realizar a comparação das marcações de diversos fosfonatos (Metileno disfofonato de Sódio MDP, Ácido Etilenodiaminotetrametilenofosfônico EDTMP, e do diclorometilenobifosfonato de sódio - Clodronato) com 188Re para terapia de metastáses ósseas. Fosfonatos são inibidores da reabsorção óssea osteoclástica e são efetivos neste tratamento. As marcações do MDP, EDTMP e Clodronato com 188Re foram otimizadas utilizando como agente redutor o cloreto estanoso (SnCl2 2H2O) e como agente estabilizante o ácido ascórbico. As variáveis estudadas foram massa do ligante, massa do SnCl2.2H2O, massa do ácido ascórbico, tempo, pH e temperatura da reação. Os resultados mostraram que se obteve um excelente rendimento de marcação de 98% para o 188Re-MDP, de 83% para o 188Re-EDTMP e 85% para o 188Re-Clodronato. / The wide application of radiopharmaceuticals in nuclear medicine, representing 95% of procedures performed is in diagnosis, but in recent years, its application in therapeutic procedures has grown considerably. The radionuclides that emit ionizing particles (α, β, and Auger electrons) are indicated for the treatment of tumors. Malignant tumors account for approximately 12% of deaths and represent the third cause of mortality in Brazil. 188Re is one of the most attractive radioisotopes for a variety of therapeutic applications in nuclear medicine, oncology and cardiology interventions, is fully favorable and convenient because it is carrier free and can be obtained inexpensively in the form of a generator of 188W/188Re, and has a physical half-life of 16.9 hours and 100% of β-radiation emission. From the 2000s several investigations have been conducted involving molecules labeled with 188Re. Metastatic tumors are the most common form of malignancy in the skeleton. In metastatic cases the main goals of treatment are the prevention of pathological fractures and the promotion of survival with maximum preservation of function allowing the patient to maintain the greatest possible mobility and pain control. The objective of this study was to compare the labeling of various phosphonates (Sodium methylene diphosphonate - MDP, Ethylenediaminetetramethylene phosphonic acid - EDTMP, and sodium dichloromethylenediphosphonate - clodronate) with 188Re for bone metastases therapy. Phosphonates are inhibitors of osteoclastic bone resorption and are effective in treatment. The labeling of MDP, EDTMP and Clodronate with 188Re was optimized using stannous chloride (SnCl2·2H2O) as reducing agent, and ascorbic acid as stabilizing agent. The variables studied were the ligand mass, SnCl2.2H2O mass, mass of ascorbic acid, time, pH and temperature of the reaction. The results showed an excellent labeling yield of 98% for 188Re-MDP, 83% for 188Re-EDTMP and 85% for 188Re-Clodronate.

Thesis written in co-mentorship with director: Nelly Huynh; co-directors: Frank Rauch and Jean-Marc Retrouvey; collaborators: Clarice Nishio, Duy-Dat Vu and Nathalie Alos / Introduction - L'ostéogenèse imparfaite (OI) est une maladie osseuse héréditaire qui affecte la production du collagène de type I et le remodelage osseux. Les biphosphonates sont administrés aux enfants atteints d'OI dans le but d’augmenter la masse osseuse et de réduire les fractures osseuses. Les patients atteints d’OI ont des malocclusions sévères qui affectent leur qualité de vie. Plusieurs processus biologiques de remodelage osseux qui sont nécessaires pour un mouvement dentaire orthodontique sont affectés chez les gens atteints d’OI. L'objectif de cette étude est d'évaluer le mouvement dentaire orthodontique dans un modèle de souris avec OI et traitées aux biphosphonates. Matériels et méthodes - Vingt-quatre souris femelles âgées de 10 semaines ont été divisés en 4 groupes : 1 - OI traitées par zolédronate (n=6); 2 - OI non traitées (n=6); 3 - Type sauvage traitées par zolédronate (n=6); 4 – Type sauvage non traitées (n=6) Un ressort de nickel-titane activé à 10 g de force a été cimenté entre les incisives et la 1ère molaire maxillaire droite. Le côté contralatéral a été utilisé comme témoin. Une dose de 0,05 mg de zolédronate a été administrée par voie sous-cutanée un jour avant la chirurgie. Sept jours après l'intervention, les souris ont été euthanasiées et la distance entre la 1ère et la 2e molaire a été mesurée par analyse microtomographique. Résultats - Le mouvement dentaire orthodontique était significativement plus important chez les souris OI que celles de types sauvages dans les groupes non traités (p < 0,05). Le traitement par zolédronate n'a eu aucun effet significatif sur le mouvement dentaire orthodontique au sein des groupes OI et type sauvages. Conclusions - Ces résultats suggèrent une augmentation du mouvement dentaire orthodontique chez les souris avec l’ostéogenèse imparfaite. / INTRODUCTION - Osteogenesis imperfecta (OI) is a heritable bone disorder that affects collagen type I production and bone remodeling. Orthodontic tooth movement (OTM) involves the underlying process of alveolar bone remodeling. The objective of this study is to evaluate OTM in a mouse model of OI. METHODS - Twenty four, 10 week-old female mice were divided into 4 groups: 1- OI treated with zoledronate, 2- OI untreated, 3- Wild-type (WT) treated with zoledronate and 4- WT untreated. A nickel-titanium closed coil spring (10 g) was attached between the incisors and the right maxillary 1st molar. The contralateral side was used as control. Zoledronate (0.05mg/kg) was administered sub-cutaneously 1 day prior to surgery. Seven days after the procedure, the distance between 1st – 2nd molars was measured by micro-CT. RESULTS - OI mice presented significantly more OTM than WT mice when comparing within untreated groups (p<0.05). Zoledronate treatment had no significant effect on OTM within OI and WT groups. CONCLUSIONS - These results suggest increased OTM in mice with OI. The dose of zoledronate administrated 1 day prior to surgery had no significant effect on OTM.

Dans le cadre d'une étude transversale menée sur 202 patientes ménopausées et non ménopausées,les objectifs sont de démontrer l'existence d'un lien entre ménopause et altération de l'état de santé buccodentaire. D'évaluer l'action du THM sur la morbidité dentaire et «in fine» sur la mortalité dentaire.De préciser les liens entre santé bucco-dentaire et diverses pathologies générales et d'apprécier les liens entre psychisme et soma chez les femmes ménopausées. D'apprécier l'influence des biphosphonates sur l'état de santé parodontal.De placer l'étude des liens état bucco-dentaire- ménopause dans une optique sociétale et anthropologique.La ménopause a pour conséquence une altération du parodonte (p=0,003).Le THM a une action bénéfique sur le parodonte.L'effet biologique du diabète est drastique quant à la perte des organes dentaires (p=0,050).L'étude souligne l'influence «per se» d'un mauvais état bucco-dentaire pour la pathologie coronarienne (OR=1,214). De plus,évènements stressants,sècheresse buccale,pathologies ostéo articulaires,carence hormonale sont des facteurs diversement liés de la mortalité dentaire durant cette période. Par ailleurs, il est apparu que les femmes ayant été récemment traitées pour un cancer du sein développaient plus de caries dentaires (p=0,031 OR=2,161). L'étude met en évidence les effets des biphosphonates sur l'altération du parodonte (p=0,011) malgré la prise d'un THM (p=0,020).Un milieu socioculturel aisé contribueraient à la médicalisation du phénomène physiologique.Le fait de vivre seule influerait sur la perte des organes dentaires (p=0,035). Enfin,la pratique régulière d'un sport améliorerait l'état de santé orale (p=0,036). / In a cross-sectional study of 202 postmenopausal and premenopausal women,the objectives of this study are to demonstrate a link between menopause and altered state of oral health.To evaluate the action of HRT on dental disease and finally on the tooth mortality. To assess and clarify the relationship between oral health and various general diseases and links between psyche and soma in postmenopausal women.Also discussed was the influence of bisphosphonates on the state of periodontal health.Finally,it was decided to place the study links oral menopausal status in a social and anthropological perspective.It appears then that menopause results in an altered state of oral health,(p = 0.003).HRT has a beneficial effect on the periodontal disease.The biological effects of diabetes are related to dental mortality (p = 0.050). This study emphasize the influence "per se" a bad oral health status for coronary artery disease (OR = 1.214).In postmenopausal women, stressful events, dry mouth, joint and bone diseases, hormonal deficiency are factors variously related dental mortality during this period. Moreover, it was found that women who have recently been treated for breast cancer developed more dental caries (p = 0.031 OR = 2.161).The study related the effects of bisphosphonates on the alteration of periodontal (p = 0.011), despite taking HRT (p = 0.020).In addition,background socio-economic favored contribute to the medicalization of physiological phenomenon. The fact of living alone would affect the loss of dental organs (p = 0.035). Finally, the regular practice of a sport improve the state of oral health (p = 0.036).