ULTRASOUND MOLECULAR IMAGING FOR THE GUIDANCE OF ULTRASOUND-TRIGGERED RELEASE OF LIPOSOMAL DOXORUBICIN AND ITS TREATMENT MONITORING IN AN ORTHOTOPIC PROSTATIC TUMOR MODEL IN RAT

Liposome encapsulation of drugs is an interesting approach in cancer therapy to specifically release the encapsulated drug at the desired treatment site. In addition to thermo-, pH-, light-, enzyme-or redox-respon-sive liposomes, which have had promising results in (pre-) clinical studies, ultrasound-triggered sonosensitive lip-osomes represent an exciting alternative to locally trigger the release from these cargos. Localized drug release requires precise tumor visualization to produce a targeted and ultrasound stimulus. We used ultrasound molecu-lar imaging (USMI) with BR55, a vascular endothelial growth factor receptor 2 (VEGFR2)-targeted ultrasound contrast agent, to guide ultrasound-triggered release of sonosensitive liposomes encapsulating doxorubicin (L-DXR) in an orthotopic prostatic rodent tumor model. Forty-eight hours after L-DXR injection, local release of doxorubicin was triggered with a confocal ultrasound device with two focused transducers, 1.1-MHz center fre-quency, and peak positive and negative pressures of 20.5 and 13 MPa at focus. Tumor size decreased by 20% in 2 wk with L-DXR alone (n = 9) and by 70% after treatment with L-DXR and confocal ultrasound (n = 7) (p < 0.01). The effect of doxorubicin on perfusion/vascularity and VEGFR2 expression was evaluated by USMI and immunohistochemistry of CD31 and VEGFR2 and did not reveal differences in perfusion or VEGFR2 expression in the absence or after the triggered release of liposomes. USMI can provide precise guidance for ultrasound-trig-gered release of liposomal doxorubicin mediated by a confocal ultrasound device; moreover, the combination of B-mode imaging and USMI can help to follow the response of the tumor to the therapy. (C) 2021 World Federation for Ultrasound in Medicine & Biology. All rights reserved.

Automated summary

Encapsulation of drugs in liposomes is a promising approach in cancer therapy, with ultrasound-triggered sonosensitive liposomes showing potential for localized drug release. Experimental studies in animal models have demonstrated significant reduction in tumor size after ultrasound-triggered release of liposomes, guided by USMI for precise targeting.