Figure 6.

LITT enhances therapeutic drug delivery to the brain. (A) Mice were subjected to sham or laser treatment and were injected intravenously with doxorubicin (doxo) (16 mg/kg) on post-laser day 3. Three hours later, brains were harvested and imaged via white light or fluorescence for doxo signal. (B) Brains from mice treated as in A were harvested, and brain homogenates were quantified for doxo penetration via fluorimeter. Data represent mean ± SEM. Laser treatment significantly increased parenchymal doxo compared to sham (n = 3 for each condition, t-test, *P < .01). (C) Timeline of in vivo preclinical study to test LITT plus adjuvant doxo. (D) After orthotopic implantation of luciferase-expressing GL261 cells, BLI was performed on mice before a laser or sham treatment (day 7) and after indicated treatments in the same mice (day 14). Representative BLI images are shown from 3 animals in each group (n = 5 for each condition). Control = sham treatment plus intravenous vehicle; doxo alone = sham treatment plus intravenous doxo; laser alone = laser treatment plus intravenous vehicle. (E) Quantification of BLI images from animals treated as in D is shown. Laser plus doxo caused a significant decrease in tumor burden compared to control or doxo alone (n = 5 in each condition, ANOVA, *P < .05). (F) Mice treated as in D were monitored for neurological deficit-free survival (n = 8–12 for each condition). Whereas laser treatment alone showed a modest survival benefit compared to control or doxo (log-rank test with Bonferroni, *P < .0001), laser plus doxorubicin (2 doses, 12 mg/kg on day 4 and 8 mg/kg on day 14 post-laser) substantially increased survival compared to control, doxo, or laser alone (log-rank test with Bonferroni, **P < .0001, P < .0001, P < .004, respectively).