Quantification of Tumor Vascular Permeability and Blood Volume by Positron Emission Tomography

Authors

• G Niu
• H Chen
• X Tong
• L Lang
• O Jacobson
• X Yang
• R Bai
• DO Kiesewetter
• Y Ma
• G Niu
• X Chen

Abstract

Disorganized vasculature with increased vascular permeability is one of the key features of malignant tumors. In this study, with an albumin binding, NOTA conjugated truncated Evan’s Blue (NEB) dye derived PET tracer, we aimed to establish a novel strategy for evaluating vascular permeability via non-invasive PET. Due to the high sensitivity of PET, only tracer amount of radiolabeled NEB is needed, which avoids the toxicity and facilitate complexation of NEB to serum albumin. The quantitative nature of PET guarantees the accuracy of evaluation since the PET signal was directly associated with serum albumin amount. Sixty-minute dynamic NEB PET was performed in several xenograft tumor models including INS-1 human insulinoma, SCC-UM-22B human head and neck carcinoma and U87MG human glioblastoma. The signal from NEB albumin complex within the tumor blood supply can be easily delineated by kinetic modeling or simplified linear slope differentiation of TACs from both blood and tumor. The quantitative parameter Kp based on NEB PET was substantiated by EB extraction and colorimetric assay to evaluate the level of tumor vascular permeability. The changes of tumor vasculature were successfully assessed with NEB PET in tumor models after treatment with Bevacizumab, an antigenic biologics or doxorubicin, a chemotherapeutics. The antiangiogenic effect of bevacizumab could be detected by NEB PET in U87MG tumors as early as 8 hours after therapy. This method will be helpful in evaluating vascular permeability, promoting drug delivery and monitoring tumor response to therapeutics that involve angiogenesis.

Scientific Focus Area: Cancer Biology

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