Sanches Pedro Gomes, Peters Steffie, Rossin Raffaella, Kaijzel Eric L, Que Ivo, Löwik Clemens W G M, Grüll Holger
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Department of Oncology Solutions, Philips Research Eindhoven, The Netherlands.
Bone. 2015 Jun;75:62-71. doi: 10.1016/j.bone.2015.02.002. Epub 2015 Feb 10.
Bone is one of the most common metastatic target sites in breast cancer, with more than 200 thousand new cases of invasive cancer diagnosed in the US alone in 2011. We set out to establish a multimodality imaging platform for bone metastases in small animals as a tool to non-invasively quantify metastasis growth, imaging the ensuing bone lesions and possibly the response to treatment. To this end, a mouse model of osteolytic metastatic bone tumors was characterized with SPECT/CT and MRI over time. A cell line capable of forming bone metastases, MDA-MB-231, was genetically modified to stably express the reporter gene herpes simplex virus-1 thymidine kinase (hsv-1 tk). The intracellular accumulation of the radiolabeled tracer [(123)I]FIAU promoted by HSV-1 TK specifically pinpoints the location of tumor cells which can be imaged in vivo by SPECT. First, a study using tumors implanted subcutaneously was performed. The SPECT/MRI overlays and the ex vivo γ-counting showed a linear correlation in terms of %ID/cm(3) (R(2)=0.93) and %ID/g (R(2)=0.77), respectively. Then, bone metastasis growth was imaged weekly by SPECT/CT and T2-weighted MRI over a maximum of 40 days post-intracardiac injection of tumor cells. The first activity spots detectable with SPECT, around day 20 post-cell injection, were smaller than 2mm(3) and not yet visible by MRI and increased in volume and in %ID over the weeks. Osteolytic bone lesions were visible by CT (in vivo) and μCT (ex vivo). The SPECT/MRI overlays also showed a linear correlation in terms of %ID/cm(3) (R(2)=0.86). In conclusion, a new multimodality imaging platform has been established that non-invasively combines images of active tumor areas (SPECT), tumor volume (MRI) and the corresponding bone lesions (CT and μCT). To our knowledge this is the first report where the combination of soft tissue information from MRI, bone lesions by CT, and reporter gene imaging by SPECT is used to non-invasively follow metastatic bone lesions.
骨骼是乳腺癌最常见的转移靶位点之一，仅在2011年，美国就有超过20万例浸润性癌新发病例。我们着手建立一个用于小动物骨转移的多模态成像平台，作为一种非侵入性量化转移瘤生长、对随之而来的骨病变进行成像以及可能对治疗反应进行成像的工具。为此，随着时间的推移，用SPECT/CT和MRI对溶骨性转移性骨肿瘤的小鼠模型进行了表征。一种能够形成骨转移的细胞系MDA-MB-231经过基因改造，以稳定表达报告基因单纯疱疹病毒1型胸苷激酶（hsv-1 tk）。由HSV-1 TK促进的放射性标记示踪剂[(123)I]FIAU在细胞内的积累特异性地确定了肿瘤细胞的位置，该位置可通过SPECT在体内成像。首先，进行了一项使用皮下植入肿瘤的研究。SPECT/MRI叠加图和离体γ计数分别在%ID/cm(3)（R(2)=0.93）和%ID/g（R(2)=0.77）方面显示出线性相关性。然后，在心脏内注射肿瘤细胞后的最长40天内，每周用SPECT/CT和T2加权MRI对骨转移瘤生长进行成像。在细胞注射后约20天，SPECT可检测到的首批活性斑点小于2mm(3)，MRI尚不可见，且在数周内体积和%ID均增加。溶骨性骨病变可通过CT（体内）和μCT（离体）观察到。SPECT/MRI叠加图在%ID/cm(3)方面也显示出线性相关性（R(2)=0.86）。总之，已经建立了一个新的多模态成像平台，该平台非侵入性地结合了活跃肿瘤区域（SPECT）、肿瘤体积（MRI）和相应骨病变（CT和μCT）的图像。据我们所知，这是第一份使用来自MRI的软组织信息、CT的骨病变以及SPECT的报告基因成像相结合来非侵入性跟踪转移性骨病变的报告。
