Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands.
Radiology and Nuclear Medicine, Princess Máxima Center, Utrecht, The Netherlands.
J Nucl Med. 2024 Oct 1;65(10):1597-1603. doi: 10.2967/jnumed.124.268147.
To date, the imaging and diagnosis of hepatocellular carcinoma (HCC) rely on CT/MRI, which have well-known limitations. Glypican-3 (GPC3) is a cell surface receptor highly expressed by HCC but not by normal or cirrhotic liver tissue. Here we report initial clinical results of GPC3-targeted PET imaging with [Ga]Ga-DOTA-RYZ-GPC3 (RAYZ-8009), a peptide-based GPC3 ligand in patients with known or suspected HCC. [Ga]Ga-RAYZ-8009 was obtained after labeling the peptide precursor with Ga from a Ge/Ga generator and heating at 90°C for 10 min followed by sterile filtration. After administration of [Ga]Ga-RAYZ-8009, a dynamic or static PET/CT scan was acquired between 45 min and 4 h after administration. Radiotracer uptake was measured by SUVs for the following tissues: suspected or actual HCC or hepatoblastoma lesions, non-tumor-bearing liver, renal cortex, blood pool in the left ventricle, and gastric fundus. Additionally, tumor-to-healthy-liver ratios (TLRs) were calculated. Twenty-four patients (5 patients in the dynamic protocol; 19 patients in the static protocol) were scanned. No adverse events occurred. Two patients had no lesion detected and did not have HCC during follow-up. In total, 50 lesions were detected and analyzed. The mean SUV of these lesions was 19.6 (range, 2.7-95.3), and the mean SUV was 10.1 (range, 1.0-49.2) at approximately 60 min after administration. Uptake in non-tumor-bearing liver and blood pool rapidly decreased over time and became negligible 45 min after administration (mean SUV, <1.6), with a continuous decline to 4 h after administration (mean SUV, 1.0). The opposite was observed for HCC lesions, for which SUVs and TLRs continuously increased for up to 4 h after administration. In individual lesion analysis, TLR was the highest between 60 and 120 min after administration. Uptake in the gastric fundus gradually increased for up to 45 min (to an SUV of 31.3) and decreased gradually afterward. [Ga]Ga-RAYZ-8009 is safe and allows for high-contrast imaging of GPC3-positive HCC, with rapid clearance from most normal organs. Thereby, [Ga]Ga-RAYZ-8009 is promising for HCC diagnosis and staging. Further research is warranted.
迄今为止，肝细胞癌（HCC）的影像学和诊断依赖于 CT/MRI，但这些方法存在明显的局限性。Glypican-3（GPC3）是一种在 HCC 中高度表达但在正常或肝硬化组织中不表达的细胞表面受体。在这里，我们报告了在已知或疑似 HCC 患者中使用基于肽的 GPC3 配体[Ga]Ga-DOTA-RYZ-GPC3（RAYZ-8009）进行 GPC3 靶向 PET 成像的初步临床结果。[Ga]Ga-RAYZ-8009 通过从 Ge/Ga 发生器标记肽前体获得 Ga，然后在 90°C 下加热 10 分钟，随后进行无菌过滤获得。在给予[Ga]Ga-RAYZ-8009 后，在给予后 45 分钟至 4 小时之间进行动态或静态 PET/CT 扫描。通过以下组织的 SUV 测量放射性示踪剂摄取：疑似或实际 HCC 或肝母细胞瘤病变、非肿瘤性肝脏、肾皮质、左心室血池和胃底。此外，还计算了肿瘤与健康肝脏的比值（TLRs）。24 名患者（动态方案 5 名患者；静态方案 19 名患者）接受了扫描。没有发生不良事件。两名患者没有发现病变，在随访期间没有 HCC。总共检测到 50 个病变并进行了分析。这些病变的平均 SUV 为 19.6（范围 2.7-95.3），给药后约 60 分钟 SUV 为 10.1（范围 1.0-49.2）。非肿瘤性肝脏和血池中的摄取随时间迅速减少，给药后 45 分钟变得可以忽略不计（平均 SUV<1.6），并持续下降至给药后 4 小时（平均 SUV 为 1.0）。HCC 病变则相反，SUV 和 TLR 持续增加，直至给药后 4 小时。在个别病变分析中，TLR 在给药后 60 至 120 分钟之间最高。胃底的摄取在 45 分钟内逐渐增加（达到 SUV 31.3），然后逐渐减少。[Ga]Ga-RAYZ-8009 是安全的，允许对 GPC3 阳性 HCC 进行高对比度成像，并且大多数正常器官中的清除速度很快。因此，[Ga]Ga-RAYZ-8009 有望用于 HCC 的诊断和分期。需要进一步的研究。
