# Glial tumor image-guided surgery and treatment

> **NIH NIH R01** · TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION · 2021 · $414,812

## Abstract

ABSTRACT
In spite of huge clinical efforts, and a wealth of data on tumor biology, survival from glioma has not significantly
changed in the last 25 years. Extent of resection remains the most important determinant of survival for
gliomas of all grades. However, the ability to achieve total resection is limited due to the infiltrative nature of
gliomas, making it difficult for surgeons to distinguish between tumor and normal brain tissue. Thus, it is
important to develop new imaging and drug delivery technologies to specifically image cancer cells during
surgical resection, while providing means to focally treat residual tumor deposits interspaced in normal brain.
Several strategies have been developed to improve the extent of tumor resection while limiting damage to
surrounding brain, including intraoperative MRI and fluorescence imaging. However, these methods suffer from
one or several shortcomings, such as lack of light for deep tissue penetration, not actively crossing blood-brain
barrier (BBB) and membranes of tumor cells, lack of precise overlap of white light and fluorescence images,
and/or time delayed imaging of tumor delineations. A promising recent method is based on Chlorotoxin-
Indocyanine Green (ICG) conjugate (BLZ-100, “tumor paint”, presently in phase 1 clinical trial) for improved
Targeted NIR Fluorescence Guided Resection (TFGR). However, resection alone will not be sufficient for
complete removal of infiltrating glioma cells without sacrificing healthy brain tissue. We hypothesize that our
novel glioma targetable imaging and treatment nanoconjugates are able to cross the BBB for guided surgery.
We also hypothesize that similar nanoconjugates can effectively eradicate postsurgical remnant glioma cells
inhibiting in a dual-pronged fashion the major glioblastoma markers, protein kinase CK2 and epidermal growth
factor receptor (EGFR and EGFRvIII mutant).
Specific Aim 1. Synthesis and characterization of novel glioma targetable near infrared (NIR) fluorescent
imaging agents. Nanoimaging agents PMLA/CTX/ICG and PMLA/CTX/anti-TfRmAb/ICG will be synthesized
and studied for producing intensive NIR fluorescence, suitable physico-chemical properties, synthetic
reproducibility and stability. Tumor visualization with an optimized device for clinical intra-operative NIR
fluorescence imaging will be performed to determine lead nanoconjugate for brain tumor imaging.
Specific Aim 2. Synthesis and characterization of nanoconjugates for glioblastoma multiforme treatment.
Precise glioma treatment depends on tumor-specific molecular subtype/heterogeneity verified by different
molecular markers (CK2 introduced as a novel biomarker, and EGFR/EGFRvIII highly expressed in glioma).
Specific Aim 3. Toxicity study of nanoconjugates for brain tumor imaging and treatment. To ensure translation
of the results to the clinical trial, the selected lead nanodrugs from in vitro and in vivo efficacy studies must be
examined in preparation for IND approval by FDA.

## Key facts

- **NIH application ID:** 10313261
- **Project number:** 7R01CA209921-06
- **Recipient organization:** TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION
- **Principal Investigator:** Eggehard Holler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $414,812
- **Award type:** 7
- **Project period:** 2021-05-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10313261

## Citation

> US National Institutes of Health, RePORTER application 10313261, Glial tumor image-guided surgery and treatment (7R01CA209921-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10313261. Licensed CC0.

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