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1.
Rev. med. nucl. Alasbimn j ; 13(53)jul. 2011. ilus, tab, graf
Artigo em Espanhol | LILACS | ID: lil-609888

RESUMO

Los radiofármacos con afinidad por el tejido óseo como el ácido etilen-diamino-tetrametilen-fosfónico (EDTMP) marcado con radioisótopos emisores beta- han demostrado su eficacia en el tratamiento paliativo de las metástasis óseas. Se realizó un estudio biocinético y dosimétrico del 177Lu-EDTMP en ratones NIH. Los resultados obtenidos fueron extrapolados a humanos. Se estimó la dosis absorbida en órganos para dos modelos: un hombre adulto y una mujer adulta. El 177Lu-EDTMP posee una selectiva captación en hueso, una rápida eliminación en sangre e insignificante captación en tejidos no óseos. La dosis en hueso estimada para el hombre se encuentra entre 14,7-15,3 cGy/mCi y entre 19,6-20,4 cGy/mCi para la mujer. La toxicidad en médula ósea representa el factor limitante de este tipo de terapia, y para evitar superar la dosis máxima que ésta puede tolerar (200 cGy), se encontró que la actividad máxima segura de 177Lu-EDTMP que puede ser inyectada al hombre (73,9Kg), corresponde a un valor de 1,01 mCi/kg y a un valor de 1,25 mCi/Kg para la mujer (56,9Kg).


Bone-seeking radiopharmaceuticals like the ethylenediaminetetramethylene phosphonic acid (EDTMP) labeled with beta--emitting radioisotopes have demonstrated their efficacy in the palliative treatment of skeletal metastasis. A biokinetic and dosimetric study of 177Lu-EDTMP in NIH mice was performed. The results obtained were extrapolated to human. We estimate the absorbed doses in organs for two models: an adult male and an adult female. 177Lu-EDTMP has a selective uptake in bone, a rapid elimination from blood and negligible uptake in non-skeletal tissues. The estimated dose in bone is between 14.7-15.3 cGy/mCi for men and between 19.6-20.4 cGy/mCi for women. Bone marrow toxicity represents the limiting factor in this kind of therapy, and to avoid exceed the maximum dose it can tolerate (200 cGy), it was found that the maximum safe activity of 177Lu-EDTMP to be injected to male (73.9 kg), corresponds to a value of 1.01 mCi/kg and a value of 1.25 mCi/kg for female (56.9 kg).


Assuntos
Humanos , Animais , Masculino , Feminino , Camundongos , Compostos Organofosforados/farmacocinética , Compostos Organometálicos/farmacocinética , Lutécio/farmacocinética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Radioisótopos/farmacocinética , Cuidados Paliativos , Compostos Organofosforados/uso terapêutico , Compostos Organometálicos/uso terapêutico , Distribuição Tecidual , Dor/radioterapia , Lutécio/uso terapêutico , Modelos Biológicos , Radioisótopos/uso terapêutico
2.
Rev. med. nucl. Alasbimn j ; 12(49)July 2010.
Artigo em Espanhol | LILACS | ID: lil-580223

RESUMO

Introducción: El péptido Sustancia P (SP) es el ligando principal de los receptores de neurokininas tipo 1, los cuales se encuentran sobreexpresados en los gliomas malignos. Método: Se obtuvo 177Lu-DOTA-SP con elevada pureza radioquímica. Se realizaron biodistribuciones en ratones normales a diferentes tiempos. Se calcularon las dosis absorbidas para los diferentes órganos del ratón (cGy/uCi). Utilizando los métodos de escalación por tiempo (A) y extrapolación directa (B), se obtuvieron las dosis en los diferentes órganos humanos. Se calcularon las máximas dosis tolerables en función de los órganos críticos (mCi/kg). Resultados: La máxima actividad tolerable que puede ser inyectada sin producir toxicidad en riñones es 11,2 mCi/kg (hombre adulto) y 11,4 mCi/kg (mujer adulta) según el método A y de 47,2 mCi/kg y 56,2 mCi/kg, respectivamente según el método B. Conclusiones: Hasta el momento se pudo obtener 177Lu-DOTA-SP con Ae= 0,05mCi/ ug de péptido. La misma puede aumentarse utilizando el 177LuCl3 de mayor actividad específica.


Introduction: Substance P (SP) is the main ligand of neurokin type 1 receptors, which are consistently overexpressed in malignant gliomas. Method: 177Lu-DOTA-SP was obtained with high radiochemical purity. Biodistribution in normal mice at different times, were done. Absorbed doses were calculated for different mice organs (cGy/uCi). Absorbed doses in human organs were calculated using two different methods, time scaling (A) and data extrapolation (B). Maximum tolerated doses were calculated according to critical organs (mCi/kg). Results: Maximum tolerated dose that can be injected without kidney toxicity is 11,2 mCi/kg (adult man) and 11,4 mCi/kg (adult woman) according to method A and 47,2 mCi/kg, 56,2 mCi/kg, respectively according to method B. Conclusion: So far, 177Lu-DOTA-SP was achieved with a specific activity (S.a) of 0,05 mCi/ ug of peptide. This S.a can be increased using 177LuCl3 of higher specific activity.


Assuntos
Humanos , Masculino , Animais , Feminino , Camundongos , Lutécio/farmacocinética , Radioisótopos/farmacocinética , Substância P/farmacocinética , Distribuição Tecidual , Doses de Radiação , Estabilidade de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Fatores de Tempo , Radiometria , Receptores de Peptídeos/administração & dosagem
3.
Rev. med. nucl. Alasbimn j ; 7(28)apr. 2005. tab, graf
Artigo em Inglês | LILACS | ID: lil-444064

RESUMO

The labeling with 177Lu and quality control procedures to produced DOTA (1,4,7,10-N,N´,N´´,N´´´, tetraazaciclododecane tetraacetic acid) coupled octreotate labeled peptide was evaluated. The labeling was performed using 30µg of DOTA-Tyr3-octreotate and 500 and 1110 MBq of 177Lu, buffered with sodium acetate/acetic acid 0.4M pH 4.5 for 20 minutes at 100ºC. The radiochemical purity was determined by ITLC na HPLC. Biological distribution studies were performed on Nude mices with tumours (AR42J rat pancreatic tumour cells) by invasive method. The stability of the 177Lu-DOTA-Tyr3-octreotate was followed by 7 days, and in both labeling procedures, the radiochemical purity were superior than 98 percent. Biodistribution studies showed fast blood clearance and the kidneys were the critical organs. The uptake in tumour were significant after 24 hours and the labeled peptide showed high in vivo stability.


Assuntos
Camundongos , Animais , Compostos Organometálicos/farmacocinética , Distribuição Tecidual , Estabilidade de Medicamentos , Compostos Radiofarmacêuticos/farmacocinética , Controle de Qualidade , Cromatografia Líquida de Alta Pressão , Células Tumorais Cultivadas , Lutécio/farmacocinética , Octreotida/farmacocinética , Radioisótopos/farmacocinética , Camundongos Nus , Somatostatina/análogos & derivados , Taxa de Depuração Metabólica
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