Institute for Macromolecular Chemistry, University of Freiburg, 79104, Freiburg, Germany.
Mol Imaging Biol. 2014 Jun;16(3):350-61. doi: 10.1007/s11307-013-0698-8.
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.
大鼠是研究乳腺癌转移和骨病理学的重要临床前模型。在这些研究领域，荧光分子断层扫描（FMT）常用于对小鼠进行定量三维（3D）成像。然而，由于 FMT 信号的深度依赖性和空间分辨率较强，需要在大鼠中进行验证研究。
根据从光学体模和与肿瘤成像、骨重塑以及纳米颗粒生物分布分析相关的模型中获得的 FMT/micro-CT（微计算机断层扫描）重建体积，评估大鼠中的 FMT 性能。
在 20mm 厚的光学体模内，FMT 重建结果准确（近红外荧光剂 VivoTag 750（VT750）78-2500 nM 范围内的恢复率为 95±11%）、精确（CV≤8%）且线性（R²>0.9788）。在体内，植入的明确荧光靶标可恢复 105±5%，且与 micro-CT 描绘的结构成功配准。此外，使用骨靶向成像剂 Osteosense 750，FMT 可识别的新骨形成区域可与 micro-CT 图像中观察到的骺板生长区相映射。最后，作为概念验证，通过 FMT/micro-CT 可以在 2 周内的 11 个不同时间点监测大鼠体内 VT750-白蛋白缀合物的药物药代动力学。
FMT 成像已在光学体模和 160g 大鼠中得到验证，且可将 FMT/micro-CT 序贯成像视为大鼠临床前研究的有用工具。
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