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Exposed Phosphatidylserine as a Biomarker for Clear Identification of Breast Cancer Brain Metastases in Mouse Models
Lulu Wang1, Alan H Zhao2, Chad A Arledge1
1Department of Biomedical Engineering, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Abstract:
Brain metastasis is the most common intracranial malignancy in adults. The prognosis is extremely poor, partly because most patients have more than one brain lesion, and the currently available therapies are nonspecific or inaccessible to those occult metastases due to an impermeable blood-tumor barrier (BTB). Phosphatidylserine (PS) is externalized on the surface of viable endothelial cells (ECs) in tumor blood vessels. In this study, we have applied a PS-targeting antibody to assess brain metastases in mouse models. Fluorescence microscopic imaging revealed that extensive PS exposure was found exclusively on vascular ECs of brain metastases. The highly sensitive and specific binding of the PS antibody enables individual metastases, even micrometastases containing an intact BTB, to be clearly delineated. Furthermore, the conjugation of the PS antibody with a fluorescence dye, IRDye 800CW, or a radioisotope, 125I, allowed the clear visualization of individual brain metastases by optical imaging and autoradiography, respectively. In conclusion, we demonstrated a novel strategy for targeting brain metastases based on our finding that abundant PS exposure occurs on blood vessels of brain metastases but not on normal brain, which may be useful for the development of imaging and targeted therapeutics for brain metastases.
Insights
Researchers developed a novel method to detect brain metastases by targeting externalized phosphatidylserine (PS) on tumor blood vessels. This PS-targeting antibody strategy enables clear visualization of even small brain lesions, improving diagnostic capabilities.
Area of Science:
- Oncology
- Vascular Biology
- Medical Imaging
Background:
- Brain metastasis is a frequent and severe complication of cancer in adults.
- Current therapies for brain metastases are limited by nonspecific action and the blood-tumor barrier (BTB).
- Phosphatidylserine (PS) is exposed on endothelial cells (ECs) of tumor vasculature.
Purpose of the Study:
- To investigate the potential of PS-targeting antibodies for diagnosing brain metastases.
- To evaluate the specificity and sensitivity of PS exposure as a biomarker for brain metastases.
Main Methods:
- Application of a PS-targeting antibody in mouse models of brain metastasis.
- Fluorescence microscopic imaging to detect PS exposure on brain vasculature.
- Conjugation of the PS antibody with imaging agents (IRDye 800CW, 125I) for optical imaging and autoradiography.
Main Results:
- Extensive PS exposure was exclusively observed on vascular ECs of brain metastases, not normal brain vasculature.
- The PS-targeting antibody clearly delineated individual metastases, including micrometastases with intact BTBs.
- Optical imaging and autoradiography demonstrated successful visualization of brain metastases using conjugated antibodies.
Conclusions:
- PS exposure on brain metastasis vasculature offers a novel and specific target.
- PS-targeting antibodies provide a sensitive method for delineating brain metastases.
- This strategy holds promise for developing advanced imaging and targeted therapies for brain metastases.
