Optical imaging probes in oncology

Abstract

Cancer is a complex disease, characterized by alteration of different physiological molecular processes and cellular features. Keeping this in mind, the possibility of early identification and detection of specific tumor biomarkers by non-invasive approaches could improve early diagnosis and patient management.Different molecular imaging procedures provide powerful tools for detection and non-invasive characterization of oncological lesions. Clinical studies are mainly based on the use of computed tomography, nuclear-based imaging techniques and magnetic resonance imaging. Preclinical imaging in small animal models entails the use of dedicated instruments, and beyond the already cited imaging techniques, it includes also optical imaging studies. Optical imaging strategies are based on the use of luminescent or fluorescent reporter genes or injectable fluorescent or luminescent probes that provide the possibility to study tumor features even by means of fluorescence and luminescence imaging. Currently, most of these probes are used only in animal models, but the possibility of applying some of them also in the clinics is under evaluation.The importance of tumor imaging, the ease of use of optical imaging instruments, the commercial availability of a wide range of probes as well as the continuous description of newly developed probes, demonstrate the significance of these applications. The aim of this review is providing a complete description of the possible optical imaging procedures available for the non-invasive assessment of tumor features in oncological murine models. In particular, the characteristics of both commercially available and newly developed probes will be outlined and discussed.

Keywords: biomarkers; cancer; fluorescent probes; molecular processes; tumor cell features.

Figure 1. Schematic representation of Optical Imaging

The strategies for optical imaging are based on: A. administration of probes or B. use of engineered mice expressing a reporter gene. Panel C. shows Fluorescence (dark box on the left side) or Bioluminescence Acquisition (dark box on the right side). CCD camera=Charged-Coupled Device camera.

Figure 2. Tumor processes

Schematic representation of different processes involved in tumor growth and progression, that can be visualized by using imaging techniques.

Figure 3. In vivo detection of Luciferase activity in orthotopic U251-HRE-mCherry glioma models and ex vivo validation

A. 2-D luminescence (rainbow scale) and fluorescence (red-yellow scale) images of U251-HRE-mCherry tumors in control and TMZ-treated mice at different time points. The last column is the representative 2-D images of TMZ treated mice injected with HypoxiSense680 at different time points during TMZ treatment. Images are presented with the same scale bar. B. Ex vivo immunohistochemical staining CAIX in control and treated mice. TMZ=Temozolomide; CAIX=Carbonic Anhydrase IX.

Figure 4. Optical imaging assessment of hypoxia and neoangiogenesis levels

Mice were injected with an engineered glioblastoma line expressing Luciferase under the control of a HIF-1 inducible promoter. Images represent HIF-1 activity (Luciferase activity), hypoxia establishment (Hypoxisense680) and neo-angiogenesis (Integrisense750) during time, and show an increase of both hypoxia and angiogenesis deeply related to HIF-1 activity.

Figure 5. Schematic representation of different Tumor Cell Biomarkers

The image shows the membrane localization of some molecules used as biomarkers, and the different possibilities to target them.