Validation of Fluorescence Molecular Tomography/Micro-CT Multimodal Imaging In Vivo in Rats

• DOI: 10.1007/s11307-013-0698-8
• Publication Date: 2013-10-25T13:42:59Z
• Authors: Daniel Vonwil; Jon Christensen; Sascha Fischer; Olaf Ronneberger; V. Prasad Shastri
• Keywords: Biodistribution; X-ray microtomography; Molecular Imaging; Fluorescence-lifetime imaging microscopy; Whole body imaging

Rats are important preclinical models for studying breast cancer metastasis and bone pathologies. In these research areas, fluorescence molecular tomography (FMT) is commonly applied for quantitative three-dimensional (3D) imaging in mice. However, uncertainties due to strong depth dependency of FMT signal and spatial resolution require a validation study in rats.FMT performance in rats was assessed based on co-registered FMT/micro-computed tomography (micro-CT) reconstructed volumes obtained from optical phantoms and from models relevant for tumor imaging, bone remodeling and biodistribution analysis of nanoparticles.FMT reconstructions within 20-mm-thick optical phantoms were accurate (95 ± 11 % recovery), precise (CV ≤ 8 %) and linear (R(2) > 0.9788) over a range of 78-2,500 nM of the near infrared fluorescent agent VivoTag 750 (VT(750)). In vivo, implanted defined fluorescent targets yielded a recovery of 105 ± 5 % and successfully co-registered with micro-CT delineated structures. Additionally, using the bone-targeting imaging agent Osteosense 750, regions of neo bone formation identified by FMT could be mapped to the region of epiphyseal growth plates observed in micro-CT images. Finally, as a proof of concept, to monitor nanoparticulate drug pharmacokinetics in rat subjects the accumulation/clearance of VT(750)-albumin conjugate in/from the liver was followed at 11 different time points over a period of 2 weeks by FMT/micro-CT.FMT imaging has been validated in optical phantoms as well as in 160 g rats, and sequential FMT/micro-CT imaging can be considered as a useful tool for preclinical research in rats.