Radionuclides have shown to be effective in tumour therapy. However, the side effects determine the maximum deliverable dose. Recently, it has been demonstrated that cells can be permeabilised through sonoporation using ultrasound and contrast microbubbles. The use of sonoporation in treatment of tumours may increase the anti-tumour efficacy of radionuclide treatment. The mechanisms as well as the effects sonoporation in tumour treatment strategies are still not understood. The purpose of this study is to determine the effects of ultrasound and contrast microbubbles on the internalisation of the radionuclide 111In-DOTA-Tyr3-octreotate in tumour cells. To optimize ultrasound settings for ultrasound adjunctive tumour therapy we incubated rat pancreatic CA20948 tumour cells with two dyes (MW 40 and 70 kDa). The uptake levels were compared with cells treated with ultrasound and contrast microbubbles for different ultrasound settings. The highest molecular uptake was found with addition of contrast microbubbles (ratio of 10 bubbles to 1 cell) and with the ultrasound setting: duty cycle 0.013%, mechanical index (MI) 0.42, and treatment times of 30 and 60 min. These settings were used to enhance the internalisation of 111In-DOTA-Tyr3-octreotate. We found a 160% higher internalisation of 111In-DOTA-Tyr3-octreotate by tumour cells adjunctively treated with ultrasound and contrast microbubbles compared to untreated cells. These results show that adjunctive tumour treatment with the radionuclide 111In-DOTA-Tyr 3-octreotate and ultrasound contrast microbubbles may be feasible. When using adjunctive ultrasound contrast microbubble treatment, a lower radionuclide doses are required to reach the same anti-tumour effect.

Contrast microbubbles, Radionuclide, Tumour therapy, Ultrasound
dx.doi.org/10.1016/j.ultras.2003.11.013, hdl.handle.net/1765/64136
Ultrasonics
Department of Cardio-Thoracic Surgery

van Wamel, A, Bouakaz, A, Bernard, B.F, ten Cate, F.J, & de Jong, N. (2004). Radionuclide tumour therapy with ultrasound contrast microbubbles. In Ultrasonics (Vol. 42, pp. 903–906). doi:10.1016/j.ultras.2003.11.013