R01CA255479

Development of Next Generation 2HG and Metabolic MR Imaging for Precision Oncology of Mutant IDH and Wildtype Glioma Patients

7. Project Summary/Abstract

Gliomas are rarely curable tumors with a low survival rate of 36% at five years, which is well below the average survival rate of 67.2% across all cancers, according to SEER and CBTRUS. Malignant brain tumors cause an average of 20 years of potential life lost (YPLL) for individuals diagnosed as adults, exceeding most common cancers. However, survival and YPLL have not improved for gliomas similarly to other cancers, and progress is desperately needed.

The lack of improvement in patient outcomes is not due to a lack of new discoveries, but rather limited success in translating this knowledge into clinical benefit. Important discoveries have been made over the last decade regarding key molecular mechanisms involved in glioma initiation and growth, which have been incorporated in the latest WHO classification. The primary event in glioma initiation is the IDH mutation, which has become a paradigm shift in the treatment of glioma.

Neuro-oncology experts (SNO, EANO) agree that brain imaging can accelerate clinical trials of targeted therapies and have mandated the development of molecular imaging for highly specific and sensitive glioma imaging. The long-term goal of our research is the development of non-invasive molecular imaging methods that can be used clinically in cancer patients. IDH mutations are frequent in glioma and produce high levels of the oncometabolite 2-hydroxyglutarate (2HG) that can be imaged as a biomarker for diagnosis, prognosis, prediction, guidance of surgery and radiation, response to chemotherapy, and targeted treatments.

The objective of this application is to develop fast high-resolution whole brain quantitative 2HG and metabolic imaging for diagnosis, treatment guidance, and monitoring of mutant IDH and wildtype glioma. The central hypothesis of our proposal is that advancing next-generation 2HG and metabolic imaging will enable precision oncology and accelerate clinical translation of novel targeted therapies to improve outcomes in mutant IDH and wildtype glioma patients.

Three specific aims will be performed for this:

1) Develop fast high-resolution whole-brain clinically robust 2HG and metabolic imaging.
2) Improve sensitivity, precision, accuracy, and workflow of 2HG and metabolic imaging.
3) Clinical translation of next-generation 2HG and metabolic imaging in glioma patients.

There are strong rationales for the proposed research:

1) There is no alternative in vivo imaging method specific for IDH mutations.
2) 2HG imaging is completely non-invasive, can be repeated safely without any radiation, and can provide fast and cost-effective results.
3) It provides a comprehensive evaluation of the entire tumor and healthy brain without the sampling bias of biopsies.
4) It can be performed pre-surgically and in tumors that cannot be operated.

The approach is innovative because it employs the first available whole-brain 2HG imaging method, which will be accelerated by compressed sensing, novel shim hardware to improve data quality, and transformed into a high-throughput automated tool by deep learning.

The contribution of the proposed research will be significant because it will provide clinicians with a user-friendly and precise tool for the diagnostic, guiding, and monitoring of glioma patients.

The General Hospital Corporation

TO IMPROVE SCREENING AND EARLY DETECTION STRATEGIES AND TO DEVELOP ACCURATE DIAGNOSTIC TECHNIQUES AND METHODS FOR PREDICTING THE COURSE OF DISEASE IN CANCER PATIENTS. SCREENING AND EARLY DETECTION RESEARCH INCLUDES DEVELOPMENT OF STRATEGIES TO DECREASE CANCER MORTALITY BY FINDING TUMORS EARLY WHEN THEY ARE MORE AMENABLE TO TREATMENT. DIAGNOSIS RESEARCH FOCUSES ON METHODS TO DETERMINE THE PRESENCE OF A SPECIFIC TYPE OF CANCER, TO PREDICT ITS COURSE AND RESPONSE TO THERAPY, BOTH A PARTICULAR THERAPY OR A CLASS OF AGENTS, AND TO MONITOR THE EFFECT OF THE THERAPY AND THE APPEARANCE OF DISEASE RECURRENCE. THESE METHODS INCLUDE DIAGNOSTIC IMAGING AND DIRECT ANALYSES OF SPECIMENS FROM TUMOR OR OTHER TISSUES. SUPPORT IS ALSO PROVIDED FOR ESTABLISHING AND MAINTAINING RESOURCES OF HUMAN TISSUE TO FACILITATE RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.394 - Cancer Detection and Diagnosis Research

National Cancer Institute (NCI) [HHS - NIH]

Charlestown, Massachusetts 02129 United States

Single Zip Code

Academic-Industrial Partnerships for Translation of Technologies for Diagnosis and Treatment (R01 - Clinical Trial Optional) (PAR-18-530)

Amendment Since initial award the total obligations have increased 428% from $569,946 to $3,009,508.