Abstract
Introduction: Angiogenesis plays a critical role in tumor growth. Integrin αVβ3 is a kind of cell adhesion molecule (CAM) that overexpresses on active angiogenic endothelium and glioblastoma cells. The arginine-glycin-aspartic acid (RGD) peptide is recognized to possess specific affinity with integrin αVβ3. The blood-brain barrier (BBB) is an obstacle for drugs for treating and diagnosing CNS diseases. This study utilized focused ultrasound (FUS) of low-energy burst wave in the presence of microbubbles to transiently disrupt the BBB to increase the radiotracer 131I-E[c(RGDyK)]2 delivery to brain tumor.Methods: U87MG-fLuc glioma-bearing nude mice were prepared. The radiotracer, 131I-E[c(RGDyK)]2 was prepared by iodogen method. Bioluminescence imaging (BLI) and magnetic resonance imaging (MRI) were utilized to measure tumor areas and volumes of the mice. Nano-SPECT/CT imaging was performed after administering the radiotracer into the glioma-bearing mice after sonication with focused ultrasound. Finally, quantitative autoradiography was applied to double confirm the results from fused SPECT and MRI.Results: 131I-E[c(RGDyK)]2 was obtained in high radiolabeled yield (RCP > 95%). There was a good correlation (R2 = 0.97) between BLI and MRI for monitoring the tumor volumes. The tumor sizes of experimental group and control group were controlled in ranges of 6.534±3.7 and 6.09±4.54 mm3, respectively. By SPECT/CT and MRI analyses, there was 2.03±0.32 fold increase of the tumor uptake comparing FUS (4.97±0.49 %ID/ml) with W/O FUS (2.41±0.48 %ID/ml) at 0.5 h postinjection. The tumor uptake of the FUS treated mice (2.02±0.25 %ID/ml) was found to reach 4.57±2.04 fold increase compared to that of W/O FUS mice (0.44±0.02 %ID/ml) at 24 h postinjection. Autoradiography showed that the accumulation of the radiotracer in the brain tumor of the FUS group (4.890±0.510 %ID/ml) was 2.682±0.279 fold greater than that of the W/O FUS group (1.820±0.031 %ID/ml) at 0.5 h postinjection, which was similar to SPECT/CT and MRI analysis.Conclusion: This study demonstrated that the focused ultrasound technique to disrupt BBB could enhance and probably prolong the tumor uptake of 131I-E[c(RGDyK)]2.