Multimodality imaging of tumor xenografts and metastases in mice with combined small-animal PET, small-animal CT, and bioluminescence imaging.
Multimodality imaging of tumor xenografts and metastases in mice with combined small-animal PET, small-animal CT, and bioluminescence imaging.
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发表时间：
2007-02
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通讯作者：
C. Deroose;A. De;A. Loening;P. Chow;P. Ray;A. Chatziioannou;S. Gambhir
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作者：
C. Deroose;A. De;A. Loening;P. Chow;P. Ray;A. Chatziioannou;S. Gambhir
最近的发展已经建立了小动物PET和生物发光成像（BLI）作为癌症研究的重要工具的小鼠模型的分子成像。这些成像方式的缺点之一是缺乏解剖信息。我们将小动物PET和BLI技术与小动物CT相结合，以获得具有分子和解剖信息的融合图像。方法：我们使用小动物PET/CT和BLI检测异种移植的不同细胞系和转移的黑色素瘤细胞系（A375 M-3F），已转导慢病毒载体含有三峰成像报告基因编码的融合蛋白与海肾荧光素酶，单体红色荧光蛋白，和突变型单纯疱疹病毒1型胸苷激酶。结果在小鼠异种移植模型中的验证研究显示PET和CT图像的良好配准。通过18 F-FDG PET、9-[4-（18）F-氟-3-（羟甲基）丁基]鸟嘌呤（18 F-FHBG）PET、CT和BLI检测黑色素瘤转移，并通过海肾荧光素酶和突变体胸苷激酶表达的离体测定证实。18F-FHBG PET/CT可以检测和定位CT上因对比度分辨率差而未观察到的病变，以及18F-FDG PET上因相对于18F-FHBG更高的背景摄取而未观察到的病变。结论18F-FHBG PET、小动物CT和BLI的联合应用可以灵敏地定量小鼠肿瘤负荷。该技术对于研究转移的生物学决定因素和评价新的癌症治疗方法具有潜在的用途。
UNLABELLED Recent developments have established molecular imaging of mouse models with small-animal PET and bioluminescence imaging (BLI) as an important tool in cancer research. One of the disadvantages of these imaging modalities is the lack of anatomic information. We combined small-animal PET and BLI technology with small-animal CT to obtain fusion images with both molecular and anatomic information. METHODS We used small-animal PET/CT and BLI to detect xenografts of different cell lines and metastases of a melanoma cell line (A375M-3F) that had been transduced with a lentiviral vector containing a trimodality imaging reporter gene encoding a fusion protein with Renilla luciferase, monomeric red fluorescent protein, and a mutant herpes simplex virus type 1 thymidine kinase. RESULTS Validation studies in mouse xenograft models showed a good coregistration of images from both PET and CT. Melanoma metastases were detected by 18F-FDG PET, 9-[4-(18)F-fluoro-3-(hydroxymethyl)butyl]guanine (18F-FHBG) PET, CT, and BLI and confirmed by ex vivo assays of Renilla luciferase and mutant thymidine kinase expression. 18F-FHBG PET/CT allowed detection and localization of lesions that were not seen on CT because of poor contrast resolution and were not seen on 18F-FDG PET because of higher background uptake relative to 18F-FHBG. CONCLUSION The combination of 18F-FHBG PET, small-animal CT, and BLI allows a sensitive and improved quantification of tumor burden in mice. This technique is potentially useful for the study of the biologic determinants of metastasis and for the evaluation of novel cancer treatments.