The field of molecular imaging encompasses a collection of techniques capable of noninvasively detecting and visualizing biological processes at the molecular level within living systems. By combining established and innovative techniques from areas of biology, physics, engineering, and mathematical analysis, it has become possible to study the morphological and biochemical behavior of complex, multifaceted disease processes as they develop in situ
]. This progress has been strongly driven by applications in oncology, from fundamental research into the molecular pathways involved in carcinogenesis, to clinical monitoring of response to therapy [3
]. Within this broad spectrum, the potential for molecular imaging to deliver benefits to the patient are immense, through acceleration of the drug discovery process [4
] and the provision of techniques to improve detection, diagnosis, and decision-making for personalized molecular-based treatment [5
]. Positron emission tomography (PET), single-photon-emission computed tomography (SPECT), and magnetic resonance imaging (MRI) each use different exogenously administered contrast agents and underlying physical principles to generate images with molecular specificity. Radiolabeled and magnetically-active imaging agents have been developed and approved for use in humans, enabling these techniques to become integrated into clinical practice.
While these systems have reached the clinic and begun to impact patient care, optical techniques are also emerging with unique capabilities for molecular imaging. Based on the interaction of visible and near-infrared light with tissue, optical imaging incorporates techniques ranging from sub-cellular microscopy to macroscopic photography and three-dimensional volumetric tomography. Optical molecular imaging has thus evolved in several distinct forms, spanning spatial scales from the sub-cellular to the organ level, but in each case involving a disease-specific source of contrast affecting one or more of the measurable properties of light. This contrast may arise from endogenous or exogenous sources, and be manifest in the intensity, wavelength, frequency, or polarization state of the measured optical signal. Much of the early research in optical diagnostics relied on disease to induce alterations in endogenous tissue optical properties and affect the properties of remitted light. This required fundamental understanding of the multitude of factors involved in disease progression that influenced the collected signal. Introduction of non-specific contrast agents such as fluorescein and indocyanine green provided an additional signal that enhanced particular tissue structures such as vasculature, but it is only recently that targeted exogenous agents have emerged, capable of optically labeling the molecular and biochemical events involved in neoplastic development and progression.
In the broadest sense, optical molecular imaging incorporates biomarker discovery, contrast agent synthesis, and imaging instrumentation, with a range of techniques which meet this description currently being applied across many disciplines in biology and medicine. This review focuses on progress in optical molecular imaging in oncology, within the context of visualizing established and emerging hallmarks of cancer [6
]. We begin by discussing the properties of endogenous and exogenous elements that interact with light to generate optical molecular contrast in tissue.