Imaging: Strategies, Controversies, and Opportunities

Abstract

At a Clinical and Translational Cancer Research Think Tank meeting sponsored by the American Association for Cancer Research in 2010, one of the breakout groups focused on new technologies and imaging. The discussions emphasized new opportunities in translational imaging and its role in the future, rather than established techniques that are currently in clinical practice. New imaging methods under development are changing the approach of imaging science from a focus on the anatomic description of disease to a focus on the molecular basis of disease. Broadly referred to as molecular imaging, these new strategies directly embrace the incorporation of cell and molecular biology concepts and techniques into image generation and can involve the introduction of genes into cells with the explicit intent to image the end products of gene expression with external imaging devices. These new methods hold the promise of providing clinicians with (i) robust linkages between cell and animal models and clinical trials, (ii) in vivo biomarkers that can be measured repeatedly and sequentially over time to observe dynamic disease processes and responses to treatment, and (iii) tools for preselection and patient population enrichment in phase II and III trials to improve outcomes and better direct treatment. These strategies provide real-time pharmacodynamic parameters and can be powerful tools to monitor therapeutic effects in a spatially and tissue-specific manner, which may reduce cost during drug development, because pharmacodynamic studies in animals can inform clinical trials and accelerate the translation process. The Imaging Response Assessment Team (IRAT) program serves as an example of how imaging techniques can be incorporated into clinical trials. IRATs work to advance the role of imaging in assessment of response to therapy and to increase the application of quantitative anatomic, functional, and molecular imaging endpoints in clinical trials, and imaging strategies that will lead to individualized patient care.

A targeted approach to cancer imaging and therapy

“…Molecular imaging consists of noninvasive mapping of molecular and cellular processes associated with disease progression in living systems 3,4 . The main advantage of in vivo molecular imaging is its ability to interrogate diseased tissues without biopsies or surgical procedures, and with information in hand, a more personalized treatment regimen can be applied 5 .…”

Illuminating Cancer Systems with Genetically Engineered Mouse Models and Coupled Luciferase ReportersIn Vivo

“…Optical imaging of genetically-encoded reporters can provide image contrast through, 1) reporter-mediated enzymatic activation of an optically silent substrate (e.g., light-producing luciferase-based oxidation of D-luciferin in the presence of Mg 2+ , ATP, and O 2 ) (22, 26), 2) photo-excitation signal production (e.g., fluorescent proteins) (23), or 3) reporter-mediated enzymatic release/trapping of optically-tuned leaving groups (e.g., β-glucuronidase-mediated hydrolysis of glucuronide groups coupled to NIR imaging dyes (27)). Nuclear imaging of genetically-encoded reporters can utilize, 1) enzyme-mediated modification of a labeled substrate causing intracellular accumulation or proximal cell association (e.g., HSV1-TK-mediated phosphorylation of radiolabelled nucleosides for PET imaging) (28, 29), or 2) direct import of a labeled tracer (e.g., sodium iodide transporters/radioiodines for PET/SPECT) (22, 30). An early innovation for MRI was use of a galactopyranose blocking group coupled to a gadolinium-based relaxivity agent that rendered the MRI contrast agent sensitive to expression of the reporter gene β-galactosidase (31).…”

Modalities for image- and molecular-guided cancer surgery

“…Over the past decade, imaging has broadened from the conventional anatomical overview to state‐of‐the‐art methods giving a molecular description of structure or function. The overall goal of imaging is to provide a better outcome.…”