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Sneaking a peek inside DIPG

Monday, February 27, 2017

Mark M. Souweidane, MD, and CBTP researcher Uday Maachani, PhD, are two of the co-authors on the new paper describing biomarkers for DIPG.Mark M. Souweidane, M.D., and CBTP researcher Uday Maachani, Ph.D. While trying to tackle a deadly form of pediatric brain cancer, a team of researchers at Weill Cornell Medicine and Memorial Sloan Kettering has devised a new way to scan tumors, which may have far-reaching implications.

As reported in the Weill Cornell Brain and Spine Center blog, Mark Souweidane, M.D., and colleagues have found a way to image tumors that were once difficult to see by targeting an enzyme that is often overexpressed. 

DIPG (diffuse intrinsic pontine glioma), which claims the lives of 150 to 200 American children each year, is so infiltrative and amorphous that it’s nearly impossible to measure. And although MRI scans have been effective in imaging for diagnostic purposes, DIPG tumors don’t absorb contrast agents well, making them nearly impossible to see on scans. The result is that tumor growth cannot be measured as it progresses, and researchers have had no means of evaluating the effects of new treatments being tested in clinical trials. 

To solve the problem, Dr. Souweidane's team turned to another target for the imaging dyes: Poly [ADP-ribose] polymerase 1, commonly called PARP-1. The enzyme is known to be abundant in many cancers, including breast, ovarian, oral, and colorectal. In this study, a fluorescent agent attracted to PARP-1 was injected into mice with tumors to see whether the tumors would become visible during a positron-emission tomography (PET) scan. The tests indicated that the fluorescent images accurately traces the proliferation of tumors as they infiltrated regions of the brain beyond the pons.

The results hold great promise not only for future clinical trials of DIPG, but for other brain tumors and conditions as well, including radiation-induced necrosis, the researchers wrote, adding that the technique could be used for diagnosing other brain tumors or tumor progression, using quantities of contrast agent so small as to be safe even for patients undergoing a treatment regimen. 

The paper, “Biomarker Based PET Imaging of Diffuse Intrinsic Pontine Glioma in Mouse Models,” was published online in Cancer Research. Done as a collaboration among investigators from multiple departments at Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center as well as from the Department of Chemistry at Hunter College and the Ph.D. Program in Chemistry at the Graduate Center of the City University of New York, it is one of the many initiatives that have developed from Dr. Souweidane’s clinical trial testing convection-enhanced delivery (CED) of drugs to the tumor site in DIPG patients.