RESUMO
Standard ocular tumor treatment includes brachytherapy, as well as proton therapy, particularly for large melanoma tumors. However, the effects of different radiation types on the metastatic spread is not clear. We aimed at comparing ruthenium ((106)Ru, emitting ß electrons) and iodine ((125)I, γ-radiation) brachytherapy and proton beam therapy of melanoma implanted into the hamster eye on development of spontaneous lung metastases. Tumors of Bomirski Hamster Melanoma (BHM) implanted into the anterior chamber of the hamster eye grew aggressively and completely filled the anterior chamber within 8-10 days. Metastases, mainly in the lung, were found in 100% of untreated animals 30 days after enucleation. Tumors were irradiated at a dose of 3-10 Gy with a (106)Ru plaque and at a dose of 6-14 Gy using a (125)I plaque. The protons were accelerated using the AIC-144 isochronous cyclotron operating at 60 MeV. BHM tumors located in the anterior chamber of the eye were irradiated with 10 Gy, for the depth of 3.88 mm. All radiation types caused inhibition of tumor growth by about 10 days. An increase in the number of metastases was observed for 3 Gy of ß-irradiation, whereas at 10 Gy an inhibition of metastasis was found. γ-radiation reduced the metastatic mass at all applied doses, and proton beam therapy at 10 Gy also inhibited the metastastic spread. These results are discussed in the context of recent clinical and molecular data on radiation effects on metastasis.
Assuntos
Braquiterapia/métodos , Neoplasias Oculares/radioterapia , Neoplasias Pulmonares/prevenção & controle , Melanoma/prevenção & controle , Neoplasias Experimentais/radioterapia , Animais , Câmara Anterior/patologia , Câmara Anterior/efeitos da radiação , Partículas beta , Cricetinae , Relação Dose-Resposta à Radiação , Neoplasias Oculares/patologia , Feminino , Raios gama , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/secundário , Melanoma/radioterapia , Melanoma/secundário , Neoplasias Experimentais/patologia , PrótonsRESUMO
Chlorins have intense red absorptions and high tumor affinities that make them interesting candidates for photodynamic therapy (PDT) of cancer. This paper reports cytotoxicity, phototoxicity, in vitro cellular uptake, and in vivo biodistribution and PDT efficacy of a synthetic chlorin derivative (TCPCSO3H) towards Cloudman melanoma cells (S91). No cytotoxic effects were observed in vitro at concentrations up to 20â µm, and no toxicity was observed in vivo in DBA mice with doses up to 2â mg kg⻹. Pharmacokinetics and biodistribution of TCPCSO3H were evaluated in vivo in DBA mice bearing S91 tumors. TCPCSO3H demonstrated preferential accumulation in S91 mouse melanoma, with tumor-to-normal tissue ratios of 5 and 11 for muscle and skin, respectively, 24â h after intravenous injection of 2â mg kg⻹. Photodynamic therapy performed under these conditions with 70â mW cm⻲ diode laser irradiation at 655â nm for 25â min (total light dose=105â J cm⻲) resulted in scab formation, followed by temporary or permanent (>60 days) tumor remission. According to the Kaplan-Meier analysis, the median survival time of the control group was 9â days, whereas that of the treated group was 38â days.