Whole body in vivo examination of small animals by simultaneous X-Rays/optical tomography: comparison between the reconstructions obtained with different types of fluorescent labels

摘要

Small animal diffuse optical tomography is an appealing tool for the investigation of molecular events in cancer research and drug developments. The combination of the functional information brought by an optical system and the anatomical information delivered by X-Rays enables ⅰ) a fast multimodality animal examination; ⅱ) the correlation between the biodistribution of the molecular probes and the morphology of the animal; ⅲ) a more accurate optical data reconstructions by using the anatomy of the animal as a constrain in the reconstructions. A small animal multimodality tomographer for the coregistration of fluorescence optical signals and X-rays measurements is used in the present study. The optical system is composed with a CW laser and a CCD camera coupled with an appropriate combination of filters for the fluorescence detection. The animal is placed inside a transparent tube filled with an index matching fluid. The X-ray generator and detector have been positioned perpendicularly to the optical chain. Original optical calibration techniques have been developed in order to control at any time the alignment between the incident beam, the axis of the cylinder and the focus plan of the CCD. Specific developments have also been handled for obtaining the geometry correlation between optical and X-rays data reconstructions. This experimental setup is used in the present work for a study conducted on different kinds of fluorochromes for the purpose of the development of new molecular probes. The instrument is also used for in vivo biological study conducted on mice bearing tumors in the lungs, and tagged with near infrared optical probes (targeting probes such as Transferin-AlexaFluor 750 or such as RAFT-(cRGD)_4-Alexa700/Alexa750).