Ultrasensitive detection of uveal melanoma using [¹⁸F]AlF-NOTA-PRGD2 PET imaging.

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-07-05 DOI:10.1186/s13550-024-01123-4

Ling Wang, Xue Zhu, Yan Xue, Zhihong Huang, Wenjun Zou, Zhengwei Zhang, Mengxi Yu, Donghui Pan, Ke Wang

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Abstract

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.

Conclusion: [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.

Trial registration: ClinicalTrials.gov: NCT02441972, Registered 1 January 2012, https://clinicaltrials.gov/study/NCT02441972 .

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利用[18F]AlF-NOTA-PRGD2 PET 成像超灵敏检测葡萄膜黑色素瘤。

背景：葡萄膜黑色素瘤（UM）是成人中最常见的原发性眼内肿瘤，早期发现对于改善该疾病的临床预后至关重要。本研究评估了[18F]AlF-NOTA-PRGD2（一种在研药品）正电子发射断层扫描（PET）成像在 UM 异种移植和 UM 患者中的诊断效果。在 92-1 UM 细胞系中评估了[18F]AlF-NOTA-PRGD2 的细胞摄取、细胞结合能力和体外稳定性。在 92-1 UM 异种移植中进行了 [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，评估[18F]AlF-NOTA-PRGD2 PET 成像的诊断效果（clinicaltrials.gov 批准号：NCT02441972）。此外，还比较了[18F]AlF-NOTA-PRGD2和18F标记的氟脱氧葡萄糖（[18F]FDG）PET成像在UM异种移植物和UM患者中的应用：体外数据显示，[18F]AlF-NOTA-PRGD2 在 92-1 UM 细胞系中具有较高的细胞摄取率、细胞结合能力和体外稳定性。体内数据表明，[18F]AlF-NOTA-PRGD2示踪剂在皮下和眼部原发性UM异种移植模型中注射后60分钟，92-1 UM肿瘤清晰可见。动物模型构建7天后，这两个组织位置的肿瘤对示踪剂的吸收率分别为2.55±0.44%ID/g和1.73±0.15%ID/g。临床数据显示，在注射[18F]AlF-NOTA-PRGD2示踪剂后60分钟，UM患者的肿瘤可清晰显现。此外，与[18F]FDG示踪剂相比，[18F]AlF-NOTA-PRGD2示踪剂在UM异种移植和UM患者的PET成像中显示出更高的灵敏度和特异性：结论：与[18F]FDG PET 成像相比，[18F]AlF-NOTA-PRGD2 PET 成像可能是诊断原发性 UM 的首选方法。此外，由于肿瘤与背景的比值较高，[18F]AlF-NOTA-PRGD2 PET 成像似乎也适用于诊断有肝转移的 UM 患者：试验注册：ClinicalTrials.gov：试验注册：ClinicalTrials.gov：NCT02441972，注册日期：2012年1月1日，https://clinicaltrials.gov/study/NCT02441972 。

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