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Low-level whole-brain radiation enhances theranostic potential of single-domain antibody fragments for human epidermal growth factor receptor type 2 (HER2)-positive brain metastases. | LitMetric

AI Article Synopsis

  • Single-domain antibody fragments, known as VH, have potential for treating brain tumors, but getting them through the tumor-brain barrier is tough.
  • This study looked at using low-dose whole-brain irradiation to help deliver an anti-HER2 VH to breast cancer tumors in mice, showing that radiation increased the uptake of this therapeutic antibody in the tumors.
  • Results indicated that after 10-Gy cranial irradiation, there was enhanced tumor perfusion and permeability, leading to greater delivery of the anti-HER2 VH, suggesting this method could improve detection and treatment of brain metastases.

Article Abstract

Background: Single-domain antibody fragments (aka VH, ~ 13 kDa) are promising delivery systems for brain tumor theranostics; however, achieving efficient delivery of VH to intracranial lesions remains challenging due to the tumor-brain barrier. Here, we evaluate low-dose whole-brain irradiation as a strategy to increase the delivery of an anti- human epidermal growth factor receptor type 2 (HER2) VH to breast cancer-derived intracranial tumors in mice.

Methods: Mice with intracranial HER2-positive BT474BrM3 tumors received 10-Gy fractionated cranial irradiation and were evaluated by noninvasive imaging. Anti-HER2 VH 5F7 was labeled with F, administered intravenously to irradiated mice and controls, and PET/CT imaging was conducted periodically after irradiation. Tumor uptake of F-labeled 5F7 in irradiated and control mice was compared by PET/CT image analysis and correlated with tumor volumes. In addition, longitudinal dynamic contrast-enhanced MRI (DCE-MRI) was conducted to visualize and quantify the potential effects of radiation on tumor perfusion and permeability.

Results: Increased F-labeled 5F7 intracranial tumor uptake was observed with PET in mice receiving cranial irradiation, with maximum tumor accumulation seen approximately 12 days post initial radiation treatment. No radiation-induced changes in HER2 expression were detected by Western blot, flow cytometry, or on tissue sections. DCE-MRI imaging demonstrated transiently increased tumor perfusion and permeability after irradiation, consistent with the higher tumor uptake of F-labeled anti-HER2 5F7 in irradiated mice.

Conclusion: Low-level brain irradiation induces dynamic changes in tumor vasculature that increase the intracranial tumor delivery of an anti-HER2 VH, which could facilitate the use of radiolabeled VH to detect, monitor, and treat HER2-expressing brain metastases.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476215PMC
http://dx.doi.org/10.1093/noajnl/vdac135DOI Listing

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