Correlation of [ 68 Ga]Ga-RAYZ-8009 PET/CT Uptake with Immunohistochemical Glypican-3 Expression in Hepatocellular Carcinoma: A Proof-of-Target Study

Glypican-3, a cell-surface proteoglycan, is overexpressed in most hepatocellular carcinomas (HCCs). Recently, the glypican-3–targeted PET tracer [68Ga]Ga-RAYZ-8009 was shown to enable noninvasive detection of HCC. This retrospective analysis evaluates the correlation between tumor uptake of [68Ga]Ga-RAYZ-8009 PET/CT and glypican-3 expression, as determined by immunohistochemistry. Methods: [68Ga]Ga-RAYZ-8009 PET/CT scans of 14 patients with histologically confirmed HCC were analyzed. Tracer uptake by HCC lesions was quantified by SUVmax and SUVmean. Glypican-3 expression was assessed by immunohistochemistry using the semiquantitative H-score. Correlations between PET/CT uptake and H-score were analyzed using Spearman rank correlation. Results: Of the 14 HCC lesions analyzed, 13 were visually positive on PET, with an SUVmean ranging from 1.9 to 63.7 (median, 7.1) and SUVmax ranging from 3.9 to 147.9 (median, 17.7). One extrahepatic HCC lesion did not demonstrate uptake on PET or glypican-3 expression. A strong positive correlation was observed between tracer uptake and glypican-3 expression (SUVmean: ρ = 0.72, P = 0.0048; SUVmax: ρ = 0.71, P = 0.0058). Conclusion: [68Ga]Ga-RAYZ-8009 uptake in HCC lesions is a promising biomarker for noninvasive in vivo assessment of glypican-3 expression and may support the planning and monitoring of glypican-3–targeted therapies.