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 [⁶⁸Ga]Ga-DOTA-RYZ-GPC3 (RAYZ-8009), a peptide-based GPC3 ligand in patients with known or suspected HCC. Methods: [⁶⁸Ga]Ga-RAYZ-8009 was obtained after labeling the peptide precursor with ⁶⁸Ga from a ⁶⁸Ge/⁶⁸Ga generator and heating at 90°C for 10 min followed by sterile filtration. After administration of [⁶⁸Ga]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. Results: 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_max of these lesions was 19.6 (range, 2.7–95.3), and the mean SUV_mean 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_mean, <1.6), with a continuous decline to 4 h after administration (mean SUV_mean, 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_max of 31.3) and decreased gradually afterward. Conclusion: [⁶⁸Ga]Ga-RAYZ-8009 is safe and allows for high-contrast imaging of GPC3-positive HCC, with rapid clearance from most normal organs. Thereby, [⁶⁸Ga]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，而 CT/MRI 具有众所周知的局限性。Glypican-3 （GPC3） 是一种细胞表面受体，在 HCC 中高度表达，但在正常或肝硬化组织中不高表达。在这里，我们报告了 [68 Ga]Ga-DOTA-RYZ-GPC3 （RAYZ-8009） 靶向 GPC3 靶向 PET 成像的初步临床结果，[⁶⁸Ga]Ga-DOTA-RYZ-GPC3 （RAYZ-8009） 是一种基于肽的 GPC3 配体，适用于已知或疑似 HCC 患者。方法：用 ⁶⁸Ge/⁶⁸Ga 发生器中的 ⁶⁸Ga 标记肽前体，并在 90°C 下加热 10 分钟，然后无菌过滤后得到 [⁶⁸Ga]Ga-RAYZ-8009。施用 [⁶⁸Ga]Ga-RAYZ-8009 后，在给药后 45 分钟至 4 小时之间获得动态或静态 PET/CT 扫描。通过 SUV 测量以下组织的放射性示踪剂摄取： 疑似或实际 HCC 或肝母细胞瘤病变、非荷瘤肝脏、肾皮层、左心室血池和胃底。此外，还计算了肿瘤与健康肝脏的比率 （TLR）。结果：扫描了 24 例患者 （动态方案中 5 例患者;静态方案中 19 例患者）。未发生不良事件。2 例患者未检测到病灶，随访期间未发生 HCC。总共检测和分析了 50 个病灶。给药后约 60 分钟，这些病变的平均 SUV_最大值为 19.6 （范围，2.7-95.3），平均 SUV_平均值为 10.1 （范围，1.0-49.2）。非荷瘤肝脏和血池的摄取随着时间的推移迅速下降，给药后 45 分钟变得可以忽略不计（平均 SUV_平均值，<1。6），给药后持续下降至 4 小时 （平均 SUV_平均值，1.0）。HCC 病灶观察到相反的情况，其中 SUVs 和 TLRs 在给药后持续增加长达 4 h。在单个病变分析中，给药后 60 至 120 min 的 TLR 最高。胃底摄取逐渐增加长达 45 分钟 （达到 SUV_最大 31.3 分钟），之后逐渐下降。结论：[⁶⁸Ga]Ga-RAYZ-8009 是安全的，可对 GPC3 阳性 HCC 进行高对比度成像，并能从大多数正常器官中快速清除。因此，[⁶⁸Ga]Ga-RAYZ-8009 有望用于 HCC 诊断和分期。需要进一步的研究。