Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, 1161 21st Ave. S., AA 1105 MCN, Nashville, TN, 37232, USA.
Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
Mol Imaging Biol. 2018 Apr;20(2):200-204. doi: 10.1007/s11307-017-1113-7.
The identification and targeting of biomarkers specific to prostate cancer (PCa) could improve its detection. Given the high expression of translocator protein (TSPO) in PCa, we investigated the use of [F]VUIIS1008 (a novel TSPO-targeting radioligand) coupled with positron emission tomography (PET) to identify PCa in mice and to characterize their TSPO uptake.
Pten, Trp53 prostate cancer-bearing mice (n = 9, 4-6 months old) were imaged in a 7T MRI scanner for lesion localization. Within 24 h, the mice were imaged using a microPET scanner for 60 min in dynamic mode following a retro-orbital injection of ~ 18 MBq [F]VUIIS1008. Following imaging, tumors were harvested and stained with a TSPO antibody. Regions of interest (ROIs) were drawn around the tumor and muscle (hind limb) in the PET images. Time-activity curves (TACs) were recorded over the duration of the scan for each ROI. The mean activity concentrations between 40 and 60 min post radiotracer administration between tumor and muscle were compared.
Tumor presence was confirmed by visual inspection of the MR images. The uptake of [F]VUIIS1008 in the tumors was significantly higher (p < 0.05) than that in the muscle, where the percent injected dose per unit volume for tumor was 7.1 ± 1.6 % ID/ml and that of muscle was < 1 % ID/ml. In addition, positive TSPO expression was observed in tumor tissue analysis.
The foregoing preliminary data suggest that TSPO may be a useful biomarker of PCa. Therefore, using TSPO-targeting PET ligands, such as [F]VUIIS1008, may improve PCa detectability and characterization.
鉴定和靶向前列腺癌(PCa)特异性生物标志物可以提高其检测率。鉴于转位蛋白(TSPO)在 PCa 中的高表达,我们研究了使用[F]VUIIS1008(一种新型 TSPO 靶向放射性配体)结合正电子发射断层扫描(PET)来识别小鼠中的 PCa 并对其 TSPO 摄取进行特征分析。
在 7T MRI 扫描仪中对携带 Pten、Trp53 的前列腺癌小鼠(n=9,4-6 个月龄)进行成像,以定位病变。在 24 小时内,通过眼眶后注射约 18MBq[F]VUIIS1008,使用 microPET 扫描仪以动态模式对小鼠进行 60 分钟的成像。成像后,采集肿瘤并使用 TSPO 抗体进行染色。在 PET 图像中,在肿瘤和肌肉(后肢)周围绘制感兴趣区域(ROI)。在整个扫描过程中记录每个 ROI 的时间-活性曲线(TAC)。比较肿瘤和肌肉之间在放射性示踪剂给药后 40-60 分钟的平均活性浓度。
通过对 MR 图像的直观检查证实了肿瘤的存在。[F]VUIIS1008 在肿瘤中的摄取明显更高(p<0.05),肿瘤的每单位体积注入剂量百分比(ID/ml)为 7.1±1.6%,而肌肉中的注入剂量百分比<1%。此外,在肿瘤组织分析中观察到 TSPO 的阳性表达。
上述初步数据表明 TSPO 可能是 PCa 的有用生物标志物。因此,使用 TSPO 靶向 PET 配体,如[F]VUIIS1008,可能会提高 PCa 的检测率和特征分析。