A Deeper Understanding of the Tumor Microenvironment using Simultaneous PET/MRI

While simple oncology studies such as the effect of cancer treatment on tumor volume may be performed using sequential PET and MRI1, a stable physiological or biochemical condition cannot be guaranteed between sequential scans. So there is always a greater potential for variability relative to simultaneous PET/MRI scans. For example, prolonged anesthesia has been shown to change vascular characteristics and physiology in tumors2, leading to changes in the hypoxic state of a tumor’s microenvironmental regions that can occur quite rapidly. Therefore, imaging hypoxia, angiogenesis, and apoptosis at different time points could lead to inaccurate conclusions.

An everyday analogy would be only watching one soccer team on the pitch during one half, and then only watching the opposing team during the second half. This results in a poor understanding of the teams and the game. Watching both “teams” at the same time in cancer biology will produce a much better understanding of the evolution and growth of a tumor.

A mixture of 18F-FDG PET agent and MultiHance® MRI agent was injected IV into a flank tumor model of human A549 lung cancer. The large tumor and a small portion of the mouse body are shown in this axial image orientation. Left: Average 18F-FDG PET signal overlaid on an anatomical MR image shows relative glucose uptake. Right: Dynamic Contrast Enhancement (DCE) MRI was used to construct a map of relative vascular permeability. Images courtesy of University of Arizona.

A Better Way to Study Tumor Metabolism

Simultaneous PET/MR imaging offers a way to improve anti-cancer drug studies by monitoring two synergistic biomarkers. Table 1, below, shows a few of the many PET tracers available and also a few of the many functional and molecular MRI techniques that can be paired with PET imaging in order to more accurately characterize the tumor and monitor therapy effectiveness.

Table 1, Complementary MRI techniques and PET tracers
Table 1. A wide variety of PET tracers (top row, orange) can be paired with a wide variety of MRI techniques (left column, blue) and imaged simultaneously using Cubresa’s NuPET™ and an existing MRI. The term ‘complementary biomarkers’ means the use of two different approaches that complement one another: not necessarily measuring the same thing, but rather providing two measurements that could enhance understanding about a particular phenomenon.

Obtaining a "Molecular Profile" of the Tumor

So, beyond the use of anatomical and diffusion-weighted MRI for simply localizing the tumor for a PET study, simultaneous PET/MRI provides an opportunity to observe the relationships between characteristics such as tumor hypoxia, acidosis, and angiogenesis, which are related at the molecular level3, and obtain an even more precise “molecular profile” of the tumor. DNA profiling of tumors for more effective therapy and better patient outcomes is already part of the National Cancer Institute’s definition of Precision Medicine4. The ability to observe a tumor’s behavior using more than one imaging modality at the same time, selecting the most appropriate molecular marker for the task could prove invaluable, especially for tumors that do not easily fall into well-known phenotypes.

Related Posters

O’Brien-Moran Z, , Tremblay M-L, Davis C, Rioux J, Brewer KD. Quantitative In Vivo Magnetic Resonance Imaging of Spio-Labeled Calles in a Cervical Cancer Mouse Model. -, -, -.

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Goldenberg JM, Cárdenas-Rodríguez J, Pagel MD. Assessing the Response to Therapy Using Simultaneous PET/MRI in a Preclinical Model of Pancreatic Cancer. WMIC 2017 World Molecular Imaging Congress, Philadelphia, PA, USA, September 13, 2017.

Tremblay M-L, O’Brien-Moran Z, Davis C, Brewer KD. Using molecular imaging for monitoring cancer immunotherapy success in a cervical cancer model. Beatrice Hunter Cancer Research Institution Conference, Halifax, NS, November 7-8, 2016.

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Related Research Highlights

Our research program is investigating three developments of simultaneous PET/MRI with pre-clinical tumor models.

Marty Pagel, Ph.D., Professor, Department of Cancer Systems Imaging, UT MD Anderson Cancer Center.

(1) Improving tumor diagnoses based on imaging metabolism with PET/MRI: Our goal is to improve cancer diagnoses using tumor acidosis as a noninvasive, longitudinal biomarker for cancer imaging. Glycolytic metabolism is upregulated in many solid tumors, known as the Warburg effect, which increases lactic acid production and causes acidosis of the tumor microenvironment. Other pathologies…

Combining [F18]FAZA PET and DCE MRI to evaluate anti-cancer drug treatments

Seth Gammon, Ph.D., Assistant Professor, Department of Cancer Systems Imaging, UT MD Anderson Cancer Center.

Historically we have sequentially utilized PET/CT and then MRI in both our existing projects and emerging projects. First we are utilizing PET/CT then MRI to validate new PET reporters of inflammation. While these experiments are possible and one can reasonably compare volume of interest based analysis, precise co-registration is difficult and does not leverage the…

Evaluations of oxidative phosphorylation and glycolysis metabolism in tumors using PET/MRI

Sanhita Sinharay, Ph.D., Instructor, Department of Cancer Systems Imaging, UT MD Anderson Cancer Center.

Tumor cells often show high uptake of glucose, which is used to feed the metabolic pathways of oxidative phosphorylation and glycolysis. Although glycolysis is often upregulated in tumor cells relative to normal tissues (known as the Warburg effect), oxidative phosphorylation may be upregulated or downregulated in tumors relative to normal tissues. Furthermore, the relative rates…