Theragnostic Use of 124-I Monoclonal Antibody Delivered by Convection-Enhanced Delivery for Diffuse Intrinsic Pontine Glioma in Children

Mark Souweidane, M.D.

Cornell University Medical College

Funded in June, 2010: $200000 for 3 years


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A potential new way to deliver and measure targeted immunotherapies for a deadly childhood brain tumor

Through this study, investigators will determine whether a PET imaging tracer can both deliver an experimental therapy directly to a deadly type of brain stem tumor in children, and also can accurately measure the dose that has effectively entered the tumor.

Brain stem tumors account for about 10 percent of brain tumors in children. Children with the most common form—diffuse intrinsic pontine glioma—die within a year. There is currently no effective treatment.  For the past decade, these neurosurgical investigators have undertaken pre-clinical animal research on “convection-enhanced delivery,” (CED), in which therapeutic agents are infused through a small tube that is surgically placed directly into the tumor. This approach has the potential to maximize drug concentrations in the tumor while eliminating toxicity in other tissues. They have not been able, however, to directly visualize or estimate how much of an experimental therapy delivered through CED is absorbed by the tumor. In fact, a recently failed experimental treatment administered via CED for adults with brain glioma may have reflected insufficient drug distribution to the tumor.

PET imaging may provide the capacity to measure the distribution and absorption of experimental brain tumor therapies administered via CED.  A specific PET imaging radioisotope tracer can deliver radiation to these brain stem tumor cells. Moreover, a monoclonal antibody, called “8H9” that has been found to target this brain stem tumor, links to this radioisotope. Using PET imaging, the investigators will see where the radioisotope (and therefore the attached 8H9) goes in the brain and how much radiation (and therefore 8H9) is delivered to the tumor. They hypothesize that PET imaging can serve as a “theragostic” (therapeutic and diagnostic) agent, measuring the distribution, concentration and clearance of this radioisotope-8H9 therapy. Additionally, they hypothesize that PET imaging can create a predictive model for determining ideal dosages for this and other experimental treatments administered through CED. They will undertake PET imaging in up to 18 children with this brain stem tumor participating in a Phase I clinical trial of 8H9 therapy.  Post-operative PET scanning will be performed regularly after CED of the therapy to determine its distribution and absorption by tumor tissue, and findings will be correlated with the patients’ clinical course and outcomes.

Significance: The study may lead to validating the use of PET imaging for determining appropriate dosages of experimental therapies administered directly to tumors to treat currently incurable brain gliomas in children and adults.