A Novel Imaging Strategy to Optimize Brain Tumor Immunotherapy
NINDS - National Institute of Neurological Disorders and Stroke
About This Grant
ABSTRACT. Immunotherapy has emerged as a successful therapeutic strategy for a variety of cancers. The recent success of immunotherapies in other solid tumors has sparked increased attention to treatments targeting the immune system in glioblastoma (GBM) and other brain cancers. One of the key challenges in the successful treatment of brain tumors with immunotherapy is our lack of appropriate methods to visualize and quantify the killing of cancer cells by the immune system within the brain. Currently, contrast-enhanced magnetic resonance imaging (MRI) is used to evaluate treatment response and progression in these patients. However, the accurate determination of tumor progression from treatment-associated inflammation, remains an unmet clinical challenge. The lack of a useful response assessment has complicated patient care and the clinical development of these therapies. This proposal aims to address this by developing a novel imaging strategy to visualize and quantify the specific protein, known as perforin, which immune cells utilize to gain access to kill cancer cells. Herein, we will develop a first-in-class, small molecule positron emission tomography (PET) probe which is capable of passively crossing the blood brain barrier and binding to perforin, permitting differentiation between response to immunotherapy and non-response. This strategy would permit non-invasive visualization of perforin levels with minimal off-target activity as perforin is expressed exclusively by cytotoxic cells of the immune system. We will develop a library of novel fluorine-containing small molecules targeting perforin and advance the top 10 binding molecules for radiolabeling with fluorine-18 (SA1). We will then characterize their brain penetration, biodistribution, and stability and use quantitative benchmarks to advance the top 3 performing radiotracers for treatment monitoring studies (SA2). Lastly, we will assess the utility of perforin-PET to detect therapeutic response and predict outcomes in established syngeneic orthotopic mouse models of glioblastoma following treatment with immune checkpoint blockade (SA3). Success of this approach would allow for rapid translation and incorporation into clinical studies. This would permit clinicians and researchers to visualize and have real-time information of the killing of brain cancer cells by the immune system and make informed decisions regarding the effectiveness of immunotherapy for any particular patient. The significance of the proposed research is that it demonstrates a generalizable mechanism to monitor multiple types of immunotherapy in glioblastoma and other brain tumors (including pediatric brain tumors and brain metastases). Such work has the potential to improve response determination in brain tumor immunotherapy, spare unnecessary treatment side effects, and through this eventually improve the management of this disease.
Grant Summary
A Novel Imaging Strategy to Optimize Brain Tumor Immunotherapy is a NINDS - National Institute of Neurological Disorders and Stroke grant providing up to $500K for university, nonprofit, healthcare org. Applications are due 2031-01-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $500K
2031-01-31
- 1Confirm your organization is eligible for A Novel Imaging Strategy to Optimize Brain Tumor Immunotherapy from NINDS - National Institute of Neurological Disorders and Stroke, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NINDS - National Institute of Neurological Disorders and Stroke before the deadline.
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A Novel Imaging Strategy to Optimize Brain Tumor Immunotherapy: Frequently Asked Questions
Who is eligible for the A Novel Imaging Strategy to Optimize Brain Tumor Immunotherapy?
A Novel Imaging Strategy to Optimize Brain Tumor Immunotherapy is offered by NINDS - National Institute of Neurological Disorders and Stroke and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the A Novel Imaging Strategy to Optimize Brain Tumor Immunotherapy provide?
A Novel Imaging Strategy to Optimize Brain Tumor Immunotherapy provides up to $500K per award from NINDS - National Institute of Neurological Disorders and Stroke. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the A Novel Imaging Strategy to Optimize Brain Tumor Immunotherapy deadline?
Applications for A Novel Imaging Strategy to Optimize Brain Tumor Immunotherapy are due 2031-01-31 (open). Because deadlines can change, verify the date with the funder, NINDS - National Institute of Neurological Disorders and Stroke, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the A Novel Imaging Strategy to Optimize Brain Tumor Immunotherapy?
To apply for A Novel Imaging Strategy to Optimize Brain Tumor Immunotherapy, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NINDS - National Institute of Neurological Disorders and Stroke.