PURPOSE: 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. PROCEDURE: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: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. PROCEDURE: 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. RESULTS: 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. CONCLUSIONS: 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.
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