Increasing the efficiency of the retinoblastoma brachytherapy protocol with ultrasonic hyperthermia and gold nanoparticles: A rabbit model.

PURPOSE: This study purposed to evaluate the efficacy of brachytherapy with the modality of ultrasonic hyperthermia in the presence of gold nanoparticles (GNPs) on an ocular retinoblastoma tumor in an animal model of the rabbit.

MATERIALS AND METHODS: Gold nanoparticles (GNPs) were synthesized and confirmed by UV-vis spectroscopy, scanning electron microscopy and dynamic light scattering. Rabbit eyes were exposed to an ultrasonic continuous mode to reach 42 °C, and then turned into a pulse mode (40%) to maintain in the hyperthermia range (42-45 °C) for 30 min. For in vivo experiments, a retinoblastoma tumor was induced by the injection of the human cell line of Y79 in rabbit eyes (n = 41). After two weeks, tumor size reached a diameter of about 5-7 mm. Seven groups were involved: control, GNPs injection (1.69 μg/ml), hyperthermia (42-45 °C, 30 min), hyperthermia with GNPs injection, brachytherapy with I-125 (20 Gy), a combination of hyperthermia and brachytherapy, and a combination of brachytherapy and hyperthermia with GNPs injection. The tumor area was measured using B-mode ultrasound images on the zero-day and at the end of the third week following the treatment. The groups were subsequently evaluated for a histopathological study of tumor necrosis three weeks after applying the treatment protocol.

RESULTS: Y79 retinoblastoma cells with varying concentrations showed that there was no significant difference in the treatment group with a concentration of 1.69 μg/ml compared to the control group after 48 hours (P > 0.05). Consequently, in vivo experiments were conducted at a concentration of 1.69 μg/ml. The relative area changes of tumor after three weeks were 1.58, 0.69, 0.45, 0.43, 0.49, 0.34, and 0.23 in the control, GNP injection, hyperthermia, hyperthermia with GNP injection, 20 Gy brachytherapy, brachytherapy and hyperthermia, brachytherapy and hyperthermia with GNPs injection, respectively. There was a significant difference between the relative area changes of tumor in the combination group (hyperthermia and brachytherapy with GNPs) with the other study groups (P < 0.05). The results of histopathologic studies indicated that both hyperthermia and brachytherapy lead to treatment and necrosis of some living retinoblastoma cells, but result in complications such as bleeding, inflammation, and scarring in the retina. If GNPs are injected into the vitreous, even retinoblastoma necrotic cells disappear.

CONCLUSION: A combination therapy of brachytherapy and hyperthermia in the presence of GNPs reduces the relative size of the tumor. This method increases the necrosis percentage of retinoblastoma and significantly reduces the retinoblastoma mass in the rabbit eyes.