Wong Andrew W, Ormsby Eleanor, Zhang Hua, Seo Jai Woong, Mahakian Lisa M, Caskey Charles F, Ferrara Katherine W
Department of Biomedical Engineering, University of California Davis, CA 95616, USA.
Am J Nucl Med Mol Imaging. 2013;3(1):32-43. Epub 2013 Jan 5.
Conjugation of the (64)Cu PET radioisotope (t(1/2) = 12.7 hours) to long circulating liposomes enables long term liposome tracking. To evaluate the potential clinical utility of this radiotracer in diagnosis and therapeutic guidance, we compare image contrast, tumor volume, and biodistribution of (64)Cu-liposomes to metrics obtained with the dominant clinical tracer, (18)F-FDG. Twenty four female FVB mice with MET1 mammary carcinoma tumor grafts were examined. First, serial PET images were obtained with the (18)F-FDG radiotracer at 0.5 hours after injection and with the (64)Cu-liposome radiotracer at 6, 18, 24, and 48 hours after injection (n = 8). Next, paired imaging and histology were obtained at four time points: 0.5 hours after (18)F-FDG injection and 6, 24, and 48 hours after (64)Cu-liposome injection (n = 16). Tissue biodistribution was assessed with gamma counting following necropsy and tumors were paraffin embedded, sectioned, and stained with hematoxylin and eosin. The contrast ratio of images obtained using (18)F-FDG was 0.88 ± 0.01 (0.5 hours after injection), whereas with the (64)Cu-liposome radiotracer the contrast ratio was 0.78 ± 0.01, 0.89 ± 0.01, 0.88 ± 0.01, and 0.94 ± 0.01 at 6, 18, 24, and 48 hours, respectively. Estimates of tumor diameter were comparable between (64)Cu-liposomes and (18)F-FDG, (64)Cu-liposomes and necropsy, and (64)Cu-liposomes and ultrasound with Pearson's r-squared values of 0.79, 0.79, and 0.80, respectively. Heterogeneity of tumor tracer uptake was observed with both tracers, correlating with regions of necrosis on histology. The average tumor volume of 0.41 ± 0.05 cc measured with (64)Cu-liposomes was larger than that estimated with (18)F-FDG (0.28 ± 0.04 cc), with this difference apparently resulting primarily from accumulation of the radiolabeled particles in the pro-angiogenic tumor rim. The imaging of radiolabeled nanoparticles can facilitate tumor detection, identification of tumor margins, therapeutic evaluation and interventional guidance.
将（64）Cu正电子发射断层扫描（PET）放射性同位素（半衰期t(1/2) = 12.7小时）与长循环脂质体结合，可实现脂质体的长期追踪。为评估这种放射性示踪剂在诊断和治疗指导方面的潜在临床应用价值，我们将（64）Cu脂质体的图像对比度、肿瘤体积和生物分布与主要临床示踪剂（18）F-FDG所获得的指标进行了比较。对24只接种了MET1乳腺癌肿瘤移植物的雌性FVB小鼠进行了检查。首先，在注射（18）F-FDG放射性示踪剂后0.5小时以及注射（64）Cu脂质体放射性示踪剂后6、18、24和48小时获取系列PET图像（n = 8）。接下来，在四个时间点进行配对成像和组织学检查：（18）F-FDG注射后0.5小时以及（64）Cu脂质体注射后6、24和48小时（n = 16）。尸检后通过γ计数评估组织生物分布，将肿瘤进行石蜡包埋、切片，并用苏木精和伊红染色。使用（18）F-FDG获得的图像对比度在注射后0.5小时为0.88±0.01，而使用（64）Cu脂质体放射性示踪剂时，在6、18、24和48小时的对比度分别为0.78±0.01、0.89±0.01、0.88±0.01和0.94±0.01。（64）Cu脂质体与（18）F-FDG、（64）Cu脂质体与尸检以及（64）Cu脂质体与超声之间的肿瘤直径估计值具有可比性，Pearson相关系数r²值分别为0.79、0.79和0.80。两种示踪剂均观察到肿瘤示踪剂摄取的异质性，这与组织学上的坏死区域相关。用（64）Cu脂质体测量的平均肿瘤体积为0.41±0.05立方厘米，大于用（18）F-FDG估计的体积（0.28±0.04立方厘米），这种差异显然主要是由于放射性标记颗粒在促血管生成的肿瘤边缘积聚所致。放射性标记纳米颗粒的成像有助于肿瘤检测、肿瘤边缘识别、治疗评估和介入引导。
