[ 68 Ga]Ga-RAYZ-8009: A Glypican-3–Targeted Diagnostic Radiopharmaceutical for Hepatocellular Carcinoma Molecular Imaging—A First-in-Human Case Series

作者：Alex J. Poot, Constantin Lapa, Wolfgang Weber, Marnix G. E. H. Lam, Matthias Eiber, Alexander Dierks, Ralph A. Bundschuh, Arthur J. A. T. Braat · 发表于：Journal of Nuclear Medicine · 年份：2024 · DOI：10.2967/jnumed.124.268147 · 被引用次数：42 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Peptidase Inhibition and Analysis、Cancer, Hypoxia, and Metabolism

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 SUVmax of these lesions was 19.6 (range, 2.7–95.3), and the mean SUVmean 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 ...