Development of an F-18 Imaging Agent to Measure Glioma IDH1mut Expression
About This Grant
PROJECT SUMMARY The ability to non-invasively measure the mutated form of cytosolic NADP+- dependent isocitrate dehydrogenase (IDH1) activity using positron emission tomography (PET) will transform the clinical management of low-grade glioma and secondary glioblastoma multiforme (GBM). IDH1 mutations occur in more than 70% low-grade glioma and up to 85% secondary GBM. While IDH1 mutations, most commonly IDH1-R132H, are associated with significantly improved overall and progression-free survival compared to wild-type IDH1 gliomas, these mutations also profoundly alter cellular metabolism, influencing the tumor immunometabolic environment and contributing to malignant progression. Therefore, non-invasive imaging of IDH1 mutational status is paramount for the clinical diagnosis, characterization, and treatment of low- grade glioma and secondary GBM. Furthermore, the current development and translation of the IDH mutation targeted treatment with IDH1-R132H inhibitors highly depend on availability of highly sensitive and specific imaging methods to measure drug-target engagement and drug occupancy, and monitoring therapeutic efficacy without repeated biopsy. Given that there is no IDH mutation targeted imaging tracer available, the proposed exploratory R21 project aims to develop an IDH1-R132H-specific PET tracer by making 18F-AG-881 and 18F- heteroaromatic derivatives of AG-881 or vorasidenib, an IDH1-R132H inhibitor currently in clinical trial for treatment of low-grade gliomas harboring IDH1 or IDH2 mutations. In this project, we will synthesize six rationally designed 19F-heteroaromatic AG-881 analogs and evaluating their IC50 properties in IDH1-R132H transfected and IDH-WT glioma cells in vitro. Based on these results, we will develop and optimize an 18F-radiolabeling approach for the most promising probe candidates. The uptake and target engagement of the resulting ¹⁸F- labeled IDH1-R132H PET tracer candidates will then be assessed in IDH1-R132H expressing cells. To evaluate blood-brain barrier permeability, we will measure the uptake and efflux activity of each candidate. The lead 18F- IDH1-R132H probe will be selected based on: 1) the lowest IC50=<10 nM at IDH1-R132H; 2) sensitivity ratio of > 10:1 IDH1-R132H:IDRH-WT; 3) standardized uptake value (SUV) >3 in the brain; 4) lowest P-gp activity; and 5) brain clearance halftime of ≥ 30 min. We will then test and evaluate the developed probe in vivo through microPET imaging to quantify IDH1-R132H expression levels in mice bearing orthotopic tumors carrying IDH1- R132H. Tracer uptake and PET-derived measurement of the IDH1-R132H expression level will be validated through immunohistochemical analysis of excised tumor sections and correlated with ex vivo magnetic resonance measurements of D-2-Hydroxyglutarate (2-HG), a product of the IDH1-R132H mutant, in the tumor tissue. We anticipate the developed IDH1-R132H-specific PET tracer will enable: 1) confirmation of IDH1-R132H mutation status with spatial resolution not achievable through biopsy; 2) quantitative assessment of IDH1-R132H expression levels in vivo, and 3) valuation of the effectiveness of IDH1-mutant–targeted therapies and agents.
Grant Summary
Development of an F-18 Imaging Agent to Measure Glioma IDH1mut Expression is a NCI - National Cancer Institute grant providing up to $402K for university, nonprofit, healthcare org. Applications are due 2028-04-30 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $402K
2028-04-30
- 1Confirm your organization is eligible for Development of an F-18 Imaging Agent to Measure Glioma IDH1mut Expression from NCI - National Cancer Institute, 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 NCI - National Cancer Institute before the deadline.
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Development of an F-18 Imaging Agent to Measure Glioma IDH1mut Expression: Frequently Asked Questions
Who is eligible for the Development of an F-18 Imaging Agent to Measure Glioma IDH1mut Expression?
Development of an F-18 Imaging Agent to Measure Glioma IDH1mut Expression is offered by NCI - National Cancer Institute 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 Development of an F-18 Imaging Agent to Measure Glioma IDH1mut Expression provide?
Development of an F-18 Imaging Agent to Measure Glioma IDH1mut Expression provides up to $402K per award from NCI - National Cancer Institute. 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 Development of an F-18 Imaging Agent to Measure Glioma IDH1mut Expression deadline?
Applications for Development of an F-18 Imaging Agent to Measure Glioma IDH1mut Expression are due 2028-04-30 (open). Because deadlines can change, verify the date with the funder, NCI - National Cancer Institute, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Development of an F-18 Imaging Agent to Measure Glioma IDH1mut Expression?
To apply for Development of an F-18 Imaging Agent to Measure Glioma IDH1mut Expression, 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 NCI - National Cancer Institute.