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 MRI [1]Prognostic value of preoperative metabolic tumor volume measured by 18F-FDG PET/CT and MRI in patients with endometrial cancer, HH Chung, et al., Gyn Oncol 2013; 130(3):446–451., 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 tumors[2]The effects of anesthetics on tumor progression, Lin, et al., Int J Physiol Pathophysiol Pharmacol. 2013; 5(1): 1–10., 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.

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PET/MRI Images of A549 flank tumor in a mouse
Panel A shows a flank A549 lung tumor in a nude mouse with combined 18F-FDG PET uptake (signal intensity in color) and T2-weighted anatomical MRI (grayscale). Panel B shows a similar tumor image with a relative permeability map for the tumor (color code) overlaid on a corresponding anatomical MRI reference. Regions identified as necrotic were not included in the DCE MRI analysis. Image courtesy of the University of Arizona Department of Medical Imaging.

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 level[3]Targeting the Metabolic Microenvironment of Tumors, Gillies, et al., H. Lee Moffitt Cancer Center, Tampa, Florida, Adv Pharmacol. 2012; 65: 63–107., 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 Medicine[4]Treatment Algorithms Based on Tumor Molecular Profiling: The Essence of Precision Medicine Trials, Christophe Le Tourneau, MD, PhD, et al., Institut Curie, Department of Medical Oncology, Paris & … Continue reading. 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.

References

References
↑1 Prognostic value of preoperative metabolic tumor volume measured by 18F-FDG PET/CT and MRI in patients with endometrial cancer, HH Chung, et al., Gyn Oncol 2013; 130(3):446–451.
↑2 The effects of anesthetics on tumor progression, Lin, et al., Int J Physiol Pathophysiol Pharmacol. 2013; 5(1): 1–10.
↑3 Targeting the Metabolic Microenvironment of Tumors, Gillies, et al., H. Lee Moffitt Cancer Center, Tampa, Florida, Adv Pharmacol. 2012; 65: 63–107.
↑4 Treatment Algorithms Based on Tumor Molecular Profiling: The Essence of Precision Medicine Trials, Christophe Le Tourneau, MD, PhD, et al., Institut Curie, Department of Medical Oncology, Paris & Saint-Cloud, France, JNCI J Natl Cancer Inst (2016) 108 (4): djv362.