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.

Flank tumor model of MDA-­MB-­231 mammary carcinoma simultaneously imaged with PET and MRI using a NuPET™ insert installed within a 7T Bruker Biospec MRI. The 3D image was reconstructed with 0.64 mm isotropic resolution. A 2D slice of the PET scan is shown for comparison with the 2D MR image. Simultaneous with the PET scan, acidoCEST MRI was performed. The Bloch-­McConnell equations modified to include pH as a fitting parameter were used to analyze the difference between the average pre-­injection and post-injection spectra. Images courtesy of University of Arizona and MD Anderson Cancer Center.

Flank tumor model of MDA-­MB-­231 mammary carcinoma simultaneously imaged with PET and MRI using a NuPET™ insert installed within a 7T Bruker Biospec MRI. The 3D image was reconstructed with 0.64 mm isotropic resolution. A 2D slice of the PET scan is shown for comparison with the 2D MR image. Simultaneous with the PET scan, DCE MRI was performed. The dynamic change in MR signal was used to determine the relative K^trans (R^ktrans) value for each pixel using the linear reference region model with muscle used as the reference region. R^ktrans can be interpreted as the relative vascular permeability within the tumor region. Images courtesy of University of Arizona and MD Anderson Cancer Center.

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 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.

Download PET/MRI Applications White Paper (.pdf)

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