Estudio biocinético y dosimétrico de un kit de producción local de 177Lu-EDTMP para su uso como agente paliativo del dolor / Biokinetic and dosimetric study of 177Lu-EDTMP in the palliative treatment of skeletal metastasis

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).

Samarium-153 ethylenediamine tetramethylene phosphonate therapy for bone pain palliation in skeletal metastases.

BACKGROUND: Systemic therapy with radionuclides may be used for the treatment of patients with painful skeletal metastases owing to its efficacy, low cost and low toxicity. Imported radionuclides for pain palliation, like Strontium-89 are expensive; particularly for developing countries. In the Indian scenario, Samarium-153 (Sm-153) is produced in our own reactors and as a result, it is readily available and economical. AIM: We undertook this study to determine the efficacy and toxicity of single-dose Sm-153 ethylenediamine tetramethylene phosphonate as a palliative treatment for painful skeletal metastases. MATERIALS AND METHODS: Eightysix patients with painful skeletal metastases from various primaries, were treated with Sm-153 EDTMP at a dose of 37 MBq/kg. The effects were evaluated according to change in visual analogue pain score, analgesic consumption, Karnofsky performance score, mobility score and blood count tests, conducted regularly for 16 weeks. STATISTICS: Repeated measures analysis. RESULTS: The overall response rates were 73%, while complete response was seen in 12.4%. Reduction in analgesic consumption with improvement in Karnofsky performance score and mobility score, was seen in all responders. Response rates were 80.3 and 80.5% in breast and prostate cancer, respectively. One case, each of Wilms tumor, ovarian cancer, germ cell tumor testis, multiple myeloma, primitive neuroectodermal tumor and oesophageal cancer, did not respond to therapy. No serious side-effects were noted, except for fall in white blood cell, platelet and haemoglobin counts, which gradually returned to normal levels by six-eight weeks. CONCLUSION: Sm-153 EDTMP provided effective palliation in 73% patients with painful bone metastases: the major toxicity was temporary myelosuppression.

Treatment of bone pain secondary to metastases using samarium-153-EDTMP

CONTEXTO: Mais de 50% dos pacientes com câncer de próstata, mama ou pulmão desenvolverão dor óssea secundária a metástases. O tratamento da dor óssea metastática visa minimizar a dor, reduzir o uso de opióides e manter os movimentos. OBJETIVO: Avaliar o uso de EDTMP-153Sm para tratamento da dor óssea secundária a metástases refratária a tratamento com opióides. TIPO DE ESTUDO: Retrospectivo. LOCAL: Divisão de Medicina Nuclear, Universidade Estadual de Campinas (Unicamp). MÉTODOS: 58 pacientes foram estudados (34 homens), com média de idade de 62 anos. 31 pacientes com neoplasia de próstata, 20 com neoplasia de mama, três pacientes com câncer de pulmão, um com hemangioendotelioma de pulmão, um com adenocarcinoma de paratireóide, um com osteosarcoma e um paciente que apresentava um tumor primário desconhecido. Todos apresentavam múltiplas metástases ósseas à cintilografia óssea com MDP-99mTc e foram tratados com EDTMP-153Sm. A resposta ao tratamento foi graduada em boa (redução da dor em 50 - 100%), intermediária (25-49%) e má (0-24%). RESULTADOS: Todos os pacientes apresentavam boa captação de EDTMP-153Sm nas metástases ósseas. Dentre os doentes com câncer de próstata, resposta intermediária ou boa ocorreu em 80.6% (25 pacientes) e má resposta em 19.4% (6). Dentre os pacientes com câncer de mama, 85% (17) apresentaram resposta intermediária ou boa à terapia enquanto 15% (3) apresentaram má resposta. Todos os três pacientes com câncer de pulmão apresentaram resposta pobre ao tratamento. Os doentes com hemangioendotelioma de pulmão e com o tumor primário desconhecido apresentaram resposta intermediária ao tratamento; os pacientes com osteossarcoma e com o adenocarcinoma de paratireóide apresentaram boa resposta. Mielotoxicidade significativa não ocorreu. DISCUSSAO: O controle da dor é importante para melhorar a qualidade de vida do doente com câncer avançado. O mecanismo de alívio da dor com radionuclídeos ainda não foi elucidado, mas o tratamento é de simples administração e baixo risco de mielotoxidade. CONCLUSAO: Tratamento com EDTMP-153Sm pode controlar a dor secundária a metástases ósseas de forma efetiva na maioria dos pacientes com câncer de próstata e câncer de mama sem efeitos colaterais significativos.

Polineuropatía retardada inducida por organofosforados: reporte de un caso / Organophosphate induced delayed polyneuropathy by: Case Report

Se presenta un caso de Polineuropatía Retardada inducida por Organofosforados (PRIO) en una paciente adulta, de sexo femenino, con antecedentes de manipular desde hace ocho años insecticidas para agricultura sin protección. El diagnóstico fue confirmado por el hallazgo del insecticida organosfosforado positivo en sangre y orina, mediante el método de cromatografía en capa fina. La Neurotoxicidad retardada es una complicación que se ha observado tras el contacto con determinados tóxicos; consiste en una polineuropatía sensitivo motora de predominio axonal mas que nerviosa, que se manifiesta en forma de parestesias y debilidad distal de las extremidades. Los plaguicidas ocupan el primer lugar dentro de las causas de intoxicaciones, siendo los organofosforados y los carbamatos los de mayor incidencia de nuestro medio. Las intoxicaciones se producen por su uso frecuente en la agricultura, en zonas rurales y sin observar la protección recomendada para este tipo de actividades. Como aporte a la casuística de esta patología poco conocida en nuestro medio, presentamos este caso de la sala Santa Ana del Hospital Dos de Mayo. Palabras Claves: Polineuropatía, organofosforados y intoxicación.

A case of delayed polyneuropatlzy induced by organoplzosplzorates in an adult female patient lOith background of using insecticides in the agruculture lOithout protection since eight years is presented. Tlze diagnosis lOas confirmed by the finding of positive organophohphorated insecticides in blood and urine by means of the tlzin layers cromatography. Delayed neurotoxicity is a complication observed by the contact with some toxics. It consist of a motorsensitive polyneurophaty with axonal predominance, which usually affects to distal zone of nervous fibers and is manifested in paresthesia and distal weakness of the limbs. The first cause of intoxication is the plague combating agents, being organo-phosplzorates and carbamates which has tlze higher incidence in our environment. Intoxications are more produced in rural zones because of and inadequate protection. As a support of the causistics of this little known pathology in our environment, we reported a case in Santa Ana Service from Hospital Nacional Dos de Mayo. Key words: Polyneurophaty, organophosphorates, intoxication.

In vitro cytotoxic effect of new diphenylphosphinoethane-copper(I) complexes on human ovarian carcinoma cells.

Five new copper (I) complexes have been tested for their, in vitro cytotoxicity on chinese hamster ovary (CHO) and human ovarian carcinoma PA-1 cell lines using MTT assay. The compounds exhibited encouraging cytotoxicity at of 1, 2, 4 & 8 micrograms/ml doses. They were further tested for cytotoxicity on human ovarian carcinoma cells obtained from five different patients previously untreated with antineoplastic drugs and radiation. Standard antitumor drugs like cis-platin, adriamycin and etoposide were also included as positive control. Cytotoxicity of compounds C3, C4 and C5 (IC50 0.7, 1.25 and 1.4 micrograms/ml respectively) was found to be superior to adriamycin (IC50 2.8 micrograms/ml) but less effective than cisplatin (IC50 < 0.1 microgram/ml) on human ovarian carcinoma cells.