Abstract 2583: 68GaGa-RYZ-GPC3: A glypican-3 targeted diagnostic radiopharmaceutical for hepatocellular carcinoma molecular imaging

Abstract Introduction HCC lesions, healthy liver (HL), kidneys, blood pool activity in the left ventricle (BP) and gastric fundus. Additionally, tumor-to-healthy liver ratios (TLR) were calculated: SUVmean, HCC divided by SUVmean, HL. Results: Radiolabeling to obtain 68GaGa-RYZ-GPC3 was near quantitative, making the production highly reliable. Eleven patients (4 patients dynamic; 7 patients static protocol) were scanned. One patient did not have an HCC. Another patient had a concurrent metastatic prostate adenocarcinoma, which did not show uptake, both qualitatively and quantitatively. All HCC lesions showed uptake in qualitative assessment, even in immunohistochemistry confirmed GPC3-negative HCC lesions (3 lesions). In 23 HCC lesions, including the aforementioned GPC3-negative lesions, mean SUVmax was 17. 9 (range 2. 7-95. 3) and mean SUVmean was 10. 2 (range 1. 0-49. 2) at 60 minutes. Uptake in HL and BP decrease over time and become negligible 45 minutes after administration (SUVmean 1. 5). The opposite occurs for HCC and TLR, which continuously increase up to 4 hours after administration (TLR 4. 4 to 19. 2, at 18 minutes and 4 hours respectively). In individual lesion analysis, TLR was the highest at 60 or 120 minutes post-injection scans. Uptake in the gastric fundus, gradually increases in the first hour, and decreases gradually afterwards (SUVmean from 4. 0 to 12. 7, back to 10. 1). Conclusions: 68GaGa-RYZ-GPC3 is the first peptide based PET tracer that allows the high quality molecular imaging of HCC. Thereby 68GaGa-RYZ-GPC3 is suitable for the selective diagnosis of HCC. In addition, based on the biodistribution and in vivo dynamics on these diagnostic images, RYZ-GPC3 is very likely to hold therapeutic potential upon labeling with a therapeutic isotope (e. g 177Lu or 225Ac). Citation Format: Arthur J. A. T. Braat, Alex J. Poot, Constantin Lapa, Marnix G. E. H. Lam, Wolfgang A. Weber, Anna Karmann, Ye Yuan, Jessica Rearden, Ken Song, Ralph A. Bundschuh. 68GaGa-RYZ-GPC3: A glypican-3 targeted diagnostic radiopharmaceutical for hepatocellular carcinoma molecular imaging abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 2583.