ABSTRACT
Pancreatic adenocarcinoma is important in oncology because of its high mortality rate. Deaths may be avoided if an early diagnosis could be achieved. Several types of tumors overexpress gastrin-releasing peptide receptors (GRPr), including pancreatic cancer cells. Thus, a radiolabeled peptide derivative of gastrin-releasing peptide (GRP) may be useful as a specific imaging probe. The purpose of the present study was to evaluate the feasibility of using99mTc-HYNIC-βAla-Bombesin(7-14)as an imaging probe for Capan-1 pancreatic adenocarcinoma. Xenographic pancreatic tumor was developed in nude mice and characterized by histopathological analysis. Biodistribution studies and scintigraphic images were carried out in tumor-bearing nude mice. The two methods showed higher uptake by pancreatic tumor when compared to muscle (used as control), and the tumor-to-muscle ratio indicated that99mTc-HYNIC-βAla-Bombesin(7-14)uptake was four-fold higher in tumor cells than in other tissues. Scintigraphic images also showed a clear signal at the tumor site. The present data indicate that99mTc-HYNIC-βAla-Bombesin(7-14)may be useful for the detection of pancreatic adenocarcinoma.
Subject(s)
Animals , Humans , Male , Adenocarcinoma , Bombesin/analogs & derivatives , Organotechnetium Compounds/pharmacokinetics , Pancreatic Neoplasms , Adenocarcinoma/pathology , Bombesin/pharmacokinetics , Cell Line, Tumor , Gastrin-Releasing Peptide/analogs & derivatives , Heterografts/pathology , Heterografts , Mice, Nude , Muscles , Pancreatic Neoplasms/pathology , Peptide Fragments/pharmacokineticsABSTRACT
The objective of this work was to monitor the consolidation of the femur after osteosynthesis with a bridge plate associated with the intramedullary pin using scintigraphy. We used seven New Zealand breed male rabbits, at 4 months of age, with a mean weight of 3.5 kg. We performed a three-phase bone scintigraphy with technetium-labeled methylene diphosphonate (99mTc-MDP) before and after surgery, and 20, 50 and 90 days postoperatively. The activity index (AI) was calculated by dividing the average number of uptake counts in the region of the osteotomy by the average number of counts in the corresponding region in the contralateral limb. Radiography was performed before surgery, after surgery, and 15, 30, 45, 60 and 90 days postoperatively. We found a direct relationship between the activity index and progress of bone scintigraphy in the evaluation sequence over the period of observation. Scintigraphy allows monitoring of bone metabolism and measurement of vascularization and/or bone or tissue perfusion. The images obtained in the blood pool and static phases are the most appropriate for assessing bone metabolism in the context of this study. The bridge plate associated with the intramedullary pin promotes osteosynthesis with sufficient stability to allow bone consolidation.
A cintilografia foi empregada no acompanhamento da consolidação de osteotomia experimental do fêmur após osteossíntese com placa em ponte associada ao pino intramedular. Foram usados sete coelhos machos, raça Nova Zelândia, com massa corporal de 3,5kg e idade média de quatro meses. A cintilografia óssea trifásica com metilenodifosfonato marcado com tecnécio-99m (MDP-99mTc) foi obtida antes e após a cirurgia, e nos dias 20, 50 e 90 do pós-operatório.O índice de atividade (IA) foi calculado por meio do quociente da média do número de contagens na região da osteotomia pela média do número de contagens na região correspondente, no membro contralateral normal. Paralelamente ao estudo cintilográfico, foram realizadas radiografias antes dos procedimentos cirúrgicos e aos 15, 30, 45, 60 e 90 dias após, para acompanhamento do processo de cura óssea. Encontrou-se relação direta entre o índice de atividade e a evolução do processo de consolidação óssea na avaliação cintilográfica sequencial ao longo do período de observação. A cintilografia óssea trifásica permite acompanhar o metabolismo ósseo, avaliar e mensurar a vascularização e perfusão tecidual. As imagens obtidas na fase de pool sanguíneo e na fase óssea são as mais adequadas para avaliação do metabolismo ósseo. A placa em ponte associada com o pino intramedular promove osteossíntese com estabilidade suficiente para permitir a consolidação ossea.
Subject(s)
Animals , Fracture Fixation, Internal , Femur/anatomy & histology , Radionuclide Imaging , RabbitsABSTRACT
Purified epsilon prototoxin of Clostridium perfringens type D was produced, purified, and detoxified by the stoiechiometric method of non-radioactive iodine incorporation. Different degrees of iodination were perfomed and the toxicity of the derivatives were analysed by in vivo studies. Toxicity decreased inversely to the iodine incorporation. Eletrophoretic analysis showed different levels of stability of samples kept under different temperatures 4ºC, - 20ºC, and -80 ºC. The iodinated prototoxins were stocked for a period of four months.
A prototoxina epsílon de Clostridium perfringens tipo D foi produzida, purificada e destoxificada por estoiquiometria. Diferentes quantidades de iodo foram incorporadas à estrutura protéica da prototoxina e a toxicidade dos derivados foi analisada em estudos in vivo. Verificou-se que a toxicidade diminuiu à medida que os átomos de iodo foram incorporados à prototoxina. A análise eletroforética demonstrou a estabilidade das amostras quando armazenadas a 4ºC, -20ºC e -80ºC. A prototoxina iodada foi estocada por um período de quatro meses.
Subject(s)
Animals , Clostridium perfringens/isolation & purification , Halogenation , Toxicity/adverse effectsABSTRACT
The pharmacokinetics of scorpion venom and its toxins has been investigated in experimental models using adult animals, although, severe scorpion accidents are associated more frequently with children. We compared the effect of age on the pharmacokinetics of tityustoxin, one of the most active principles of Tityus serrulatus venom, in young male/female rats (21-22 days old, N = 5-8) and in adult male rats (150-160 days old, N = 5-8). Tityustoxin (6 µg) labeled with 99mTechnetium was administered subcutaneously to young and adult rats. The plasma concentration vs time data were subjected to non-compartmental pharmacokinetic analysis to obtain estimates of various pharmacokinetic parameters such as total body clearance (CL/F), distribution volume (Vd/F), area under the curve (AUC), and mean residence time. The data were analyzed with and without considering body weight. The data without correction for body weight showed a higher Cmax (62.30 ± 7.07 vs 12.71 ± 2.11 ng/ml, P < 0.05) and AUC (296.49 ± 21.09 vs 55.96 ± 5.41 ng h-1 ml-1, P < 0.05) and lower Tmax (0.64 ± 0.19 vs 2.44 ± 0.49 h, P < 0.05) in young rats. Furthermore, Vd/F (0.15 vs 0.42 l/kg) and CL/F (0.02 ± 0.001 vs 0.11 ± 0.01 l h-1 kg-1, P < 0.05) were lower in young rats. However, when the data were reanalyzed taking body weight into consideration, the Cmax (40.43 ± 3.25 vs 78.21 ± 11.23 ng kg-1 ml-1, P < 0.05) and AUC (182.27 ± 11.74 vs 344.62 ± 32.11 ng h-1 ml-1, P < 0.05) were lower in young rats. The clearance (0.03 ± 0.002 vs 0.02 ± 0.002 l h-1 kg-1, P < 0.05) and Vd/F (0.210 vs 0.067 l/kg) were higher in young rats. The raw data (not adjusted for body weight) strongly suggest that age plays a pivotal role in the disposition of tityustoxin. Furthermore, our results also indicate that the differences in the severity of symptoms observed in children and adults after scorpion envenomation can be explained in part by differences in the pharmacokinetics of the toxin.
Subject(s)
Animals , Male , Rats , Scorpion Venoms , Scorpions , Age Factors , Area Under Curve , Body Weight , Injections, Subcutaneous , Rats, Sprague-DawleyABSTRACT
O objetivo deste trabalho foi preparar, em condiçöes adequadas, o fármaco (DTPA) marcado com isótopo radioativo para estudos de cinrilografia renal. Além de avaliar a funçäo renal, este fármaco permite diagnosticar, precocemente, alteraçöes que indicam rejeiçäo de tecido, em casos de transplante de rins. Inicialmente, foram realizados experimentos com camundongos para investigar a distribuiçäo biológica do radiofármaco. Os resultados mostraram que, alguns minutos após a administraçäo, os rins apresentavam uma captaçäo de radioatividade. Estes dados e os resultados dos testes de esterilidade, apirogenicidade e pureza radioquímica confirmaram a qualidade do radiofármaco, permitindo o seu emprego em cintilografias de pacientes com comprometimento renal