3D fluorescence imaging of drug delivery for lung cancer therapy

Abstract

Defining appropriated models of lung tumours in mice that are similar in morphology, histopathology and molecular characteristics to human adenocarcinomas, and scaling down imaging methods to feet the small size of rodents are of the outmost importance for the pre-clinical validation of new treatments, identification of markers as well as to understand the sequences of molecular events leading to lung tumours formation. High-resolution microtomography (micro-CT) as well as 1.5 T or more importantly 4.7 T MRI are the more commonly used methods to imaging lung tumour growth in animal models. Nonetheless, these methods require expensive machines, and are providing anatomical information mainly. Near infrared fluorescence (NIRF) is commonly used in a Reflectance mode (2D), but the strong reflection of incident light and autofluorescence of the skin affects the sensitivity, especially in deep and absorbing tissues like lung, spleen or liver. We developed a fluorescence diffuse optical tomograph (fDOT) which allows fluorescence imaging even in highly attenuating and heterogeneous regions like lungs, by correcting the light propagation model from optical heterogeneities by using the transmitted excitation light measurements. It allows non-contact measurements and does not require animal immersion in an optical adaptation liquid. We used a tumour-targeted NIR probe which has been demonstrated to recognize integrin α v β 3 , a receptor over- expressed on the surface of neo-angiogenic endothelial cells. After intravenous injection of the probe to the mouse, the system records the outgoing transmitted and fluorescence light, then reconstructs the 3D fluorescence distribution resulting from the accumulation of the probe into cancerous nodules. Whereas no significant evolution were noticed using the 2D fluorescence reflectance imaging confirming that it is not adequate for such analyzes, by using the 3D imaging system, we were able to do the longitudinal follow up of lung tumour development in live animals.