四种缺氧 PET 示踪剂的影像特征和微区分布比较。
A comparison of the imaging characteristics and microregional distribution of 4 hypoxia PET tracers.
机构信息
Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York.
出版信息
J Nucl Med. 2014 Mar;55(3):515-21. doi: 10.2967/jnumed.113.126615. Epub 2014 Feb 3.
UNLABELLED
We compared the imaging characteristics and hypoxia selectivity of 4 hypoxia PET radiotracers ((18)F-fluoromisonidazole [(18)F-FMISO], (18)F-flortanidazole [(18)F-HX4], (18)F-fluoroazomycin arabinoside [(18)F-FAZA], and (64)Cu-diacetyl-bis(N4-methylsemicarbazone) [(64)Cu-ATSM]) in a single murine xenograft tumor model condition using small-animal PET imaging and combined ex vivo autoradiography and fluorescence immunohistochemistry.
METHODS
Nude mice bearing SQ20b xenograft tumors were administered 1 of 4 hypoxia PET tracers and images acquired 80-90 min after injection. Frozen sections from excised tumors were then evaluated for tracer distribution using digital autoradiography and compared with histologic markers of tumor hypoxia (pimonidazole, carbonic anydrase 9 [CA9]) and vascular perfusion (Hoechst 33342).
RESULTS
The highest tumor uptake was observed with (64)Cu-ATSM (maximum standardized uptake values [SUV(max)], 1.26 ± 0.13) and the lowest with (18)F-FAZA (SUVmax, 0.41 ± 0.24). (18)F-FMISO and (18)F-HX4 had similar intermediate tumor uptake (SUV(max), 0.76 ± 0.38 and 0.65 ± 0.19, respectively). Digital autoradiographs of hypoxia tracer distribution were compared pixel by pixel with images of immunohistochemistry stains. The fluorinated nitroimidazoles all showed radiotracer uptake increasing with pimonidazole and CA9 staining. (64)Cu-ATSM showed the opposite pattern, with highest radiotracer uptake observed in regions with the lowest pimonidazole and CA9 staining.
CONCLUSION
The fluorinated nitroimidazoles showed similar tumor distributions when compared with immunohistochemistry markers of hypoxia. Variations in tumor standardized uptake value and normal tissue distribution may determine the most appropriate clinical setting for each tracer. (64)Cu-ATSM showed the highest tumor accumulation and little renal clearance. However, the lack of correlation between (64)Cu-ATSM distribution and immunohistochemistry hypoxia markers casts some doubt on the hypoxia selectivity of (64)Cu-ATSM.
目的
在单一的小鼠异种移植肿瘤模型条件下，通过小动物 PET 成像和结合离体放射性自显影和荧光免疫组织化学，比较 4 种缺氧 PET 放射性示踪剂（[18]F-氟米索硝唑[18]F-FMISO、[18]F-氟特尼唑醇[18]F-HX4、[18]F-氟代阿霉素阿拉伯糖苷[18]F-FAZA 和 [64]Cu-二乙酰基双（N4-甲基半缩醛）[64]Cu-ATSM）的成像特征和缺氧选择性。
方法
荷 SQ20b 异种移植肿瘤的裸鼠给予 4 种缺氧 PET 示踪剂之一，并在注射后 80-90 分钟采集图像。然后，对切除的肿瘤的冷冻切片进行示踪剂分布的数字放射性自显影评估，并与肿瘤缺氧的组织学标志物（咪达唑仑、碳酸酐酶 9[CA9]）和血管灌注（Hoechst 33342）进行比较。
结果
[64]Cu-ATSM 的肿瘤摄取最高（最大标准化摄取值[SUV（max）]，1.26±0.13），[18]F-FAZA 的肿瘤摄取最低（SUV（max），0.41±0.24）。[18]F-FMISO 和 [18]F-HX4 的肿瘤摄取相似（SUV（max），0.76±0.38 和 0.65±0.19）。缺氧示踪剂分布的数字放射性自显影与免疫组织化学染色的图像逐像素进行比较。氟代硝基咪唑均显示随着咪达唑仑和 CA9 染色的增加，放射性示踪剂摄取增加。[64]Cu-ATSM 则相反，在咪达唑仑和 CA9 染色最低的区域观察到最高的放射性示踪剂摄取。
结论
氟代硝基咪唑与缺氧的免疫组织化学标志物相比，具有相似的肿瘤分布。肿瘤标准化摄取值和正常组织分布的变化可能决定每种示踪剂的最佳临床应用。[64]Cu-ATSM 显示出最高的肿瘤积累和很少的肾清除。然而，[64]Cu-ATSM 分布与免疫组织化学缺氧标志物之间缺乏相关性，这对[64]Cu-ATSM 的缺氧选择性提出了一些质疑。
Zotero 插件