Glioma is one of the most aggressive cancers, for which efficacy of conventional chemotherapy is often limited due to the blood-tumor barrier (BTB). Thus, the development of a method for enhancing the BTB permeability is strongly desired. In this study, we applied a photomechanical wave (PMW), which was generated by the irradiation of a light-absorbing material with a nanosecond laser pulse, to transiently open the BTB in a rat intracranial glioma model using C6 cells. A tumor was grown in the both hemispheres, and a solution of Evans blue (EB), as a test drug, was injected into the tail vein. Thereafter, we applied a PMW generated at a laser fluence of 0.2 J/cm2 (averaged peak pressure, ~27 MPa), 0.4 J/cm2 (~54 MPa) or 0.6 J/cm2 (~78MPa), to one hemisphere through the cranial window, while the other hemisphere served as a control. Four hours later, the rat was perfused, and we compared intensity distributions of EB fluorescence between the both hemispheres. Intensities of EB fluorescence both in the peritumoral and tumor core regions were increased with increasing the laser fluence, but hemorrhage was observed at the highest fluence. Thus, 0.4 J/cm2 would be optimum for efficient and safe BTB opening. On the basis of fluorescence microscopy with the use of enhanced green fluorescent protein-expressing C6 cells, we confirmed that a drug was delivered into targeted glioma cells in the peritumoral region. These results show the validity of the present transvascular drug delivery method to glioma.
Yusuke Akutsu, Shunichi Sato, Arata Tomiyama, Yasuyuki Tsunoi, Satoko Kawauchi, Kentaro Mori, and Mitsuhiro Terakawa, "Effective transvascular drug delivery to glioma in rats by using a pulsed laser-induced photomechanical wave
(Conference Presentation)," Proc. SPIE 9690, Clinical and Translational Neurophotonics; Neural Imaging and Sensing; and Optogenetics and Optical Manipulation, 96900H (Presented at SPIE BiOS: February 14, 2016; Published: 26 April 2016); https://doi.org/10.1117/12.2212565.4848636546001.
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