Intracranial glioma xenograft model rapidly reestablishes blood–brain barrier integrity for longitudinal imaging of tumor progression using fluorescence molecular tomography and contrast agents

摘要: Significance: The blood–brain barrier (BBB) is a major obstacle to detecting and treating brain tumors. Overcoming this challenge will facilitate the early accurate detection of lesions guide surgical resection tumors. Aim: We generated an orthotopic tumor model that simulates pathophysiology gliomas at stages; determine BBB integrity breakdown over time course progression using generic cancer-targeted near-infrared (NIR) fluorescent molecular probes. Approach: developed intracranial xenograft rapidly reestablished monitored by bioluminescence imaging. Sham control mice were injected with phosphate-buffered saline only. Fluorescence tomography (FMT) was used quantify uptake tumor-targeted passive NIR imaging agents in glioma (U87-GL-GFP PDE7B H217Q cells) model. Cancer-induced transient (with focused ultrasound, FUS) disruption dyes. Results: Stereotactic injection 50,000 cells into mouse allowed rapid reestablishment within week, as determined inability both extravasate brain. Tumor-induced observed 7 weeks after implantation. FUS achieved similar effect any point reestablishing integrity. While retention dye, indocyanine green, negligible, actively tumor-targeting exhibited selective accumulation region. probe clears from nontumor tissue exhibits higher contrast than analogous vascular-targeting agent helps delineate tumors sham control. Conclusions: highlight utility FMT for longitudinal assessment interplay between stages tumors, potential application other neurological diseases.