背景:葡萄膜黑色素瘤(UM)是成人最常见的原发性眼内肿瘤,早期发现对于改善这种疾病的临床结局至关重要。在这项研究中,评估了[18F]AlF-NOTA-PRGD2(一种研究药品)正电子发射断层扫描(PET)成像在UM异种移植物和UM患者中的诊断效果.细胞的摄取,在92-1UM细胞系中评估了[18F]AlF-NOTA-PRGD2的细胞结合能力和体外稳定性。在92-1UM异种移植物中进行[18F]AlF-NOTA-PRGD2的MicroPET成像和生物分布研究。然后,进一步招募UM患者以评估[18F]AlF-NOTA-PRGD2PET成像的诊断有效性(批准号NCT02441972inclinicaltrials.gov).此外,在UM异种移植物和UM患者中进行了[18F]AlF-NOTA-PRGD2和18F标记的氟脱氧葡萄糖([18F]FDG)PET成像的比较。
结果:体外数据显示[18F]AlF-NOTA-PRGD2具有高细胞摄取,92-1UM细胞系的细胞结合能力和体外稳定性。体内数据表明,在注射后60分钟,在皮下和眼部原代UM异种移植物模型中,用[18F]AlF-NOTA-PRGD2示踪剂清楚地观察到92-1UM肿瘤。示踪剂在这两个组织部位的肿瘤摄取率分别为2.55±0.44%ID/g和1.73±0.15%ID/g,在动物模型构建后7天。临床数据显示,注射后60分钟,[18F]AlF-NOTA-PRGD2示踪剂清楚地显示了UM患者的肿瘤。此外,与[18F]FDG示踪剂相比,[18F]AlF-NOTA-PRGD2示踪剂对UM异种移植物和UM患者的PET成像显示出更高的敏感性和特异性。
结论:与[18F]FDGPET成像相比,[18F]AlF-NOTA-PRGD2PET成像可能是诊断原发性UM的更优选方法。此外,由于高的肿瘤背景比,[18F]AlF-NOTA-PRGD2PET显像似乎也适用于诊断有肝转移的UM患者。
背景:ClinicalTrials.gov:NCT02441972,2012年1月1日注册,https://clinicaltrials.gov/study/NCT02441972。
BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and early detection is critical to improve the clinical outcome of this disease. In this study, the diagnostic effectiveness of [18F]AlF-NOTA-PRGD2 (an investigational medicinal product) positron emission tomography (PET) imaging in UM xenografts and UM patients were evaluated. The cell uptake, cell binding ability and in vitro stability of [18F]AlF-NOTA-PRGD2 were evaluated in 92-1 UM cell line. MicroPET imaging and biodistribution study of [18F]AlF-NOTA-PRGD2 were conducted in 92-1 UM xenografts. Then, UM patients were further recruited for evaluating the diagnostic effectiveness of [18F]AlF-NOTA-PRGD2 PET imaging (approval no. NCT02441972 in clinicaltrials.gov). In addition, comparison of [18F]AlF-NOTA-PRGD2 and 18F-labelled fluorodeoxyglucose ([18F]FDG) PET imaging in UM xenografts and UM patients were conducted.
RESULTS: The in vitro data showed that [18F]AlF-NOTA-PRGD2 had a high cell uptake, cell binding ability and in vitro stability in 92-1 UM cell line. The in vivo data indicated that 92-1 UM tumors were clearly visualized with the [18F]AlF-NOTA-PRGD2 tracer in the subcutaneous and ocular primary UM xenografts model at 60 min post-injection. And the tumor uptake of the tracer was 2.55 ± 0.44%ID/g and 1.73 ± 0.15%ID/g at these two tissue locations respectively, at 7 days after animal model construction. The clinical data showed that tumors in UM patients were clearly visualized with the [18F]AlF-NOTA-PRGD2 tracer at 60 min post-injection. In addition, [18F]AlF-NOTA-PRGD2 tracer showed higher sensitivity and specificity for PET imaging in UM xenografts and UM patients compared to [18F]FDG tracer.
CONCLUSIONS: [18F]AlF-NOTA-PRGD2 PET imaging may be a more preferred approach in the diagnosis of primary UM compared to [18F]FDG PET imaging. Additionally, due to the high tumor-to-background ratio, [18F]AlF-NOTA-PRGD2 PET imaging seems also to be applicable for the diagnosis of UM patients with liver metastasis.
BACKGROUND: ClinicalTrials.gov: NCT02441972, Registered 1 January 2012, https://clinicaltrials.gov/study/NCT02441972 .