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

Scholtissek, Helen; Reitsam, Nic G; Märkl, Bruno; Patt, Marianne; Dreher, Niklas; Liebich, Alessandro; Pfob, Christian H; Pranger, Bobby K et al. · J Nucl Med · 2026

retrospective_cohort · Level III

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Abstract

Glypican-3, a cell-surface proteoglycan, is overexpressed in most hepatocellular carcinomas (HCCs). Recently, the glypican-3-targeted PET tracer [<sup>68</sup>Ga]Ga-RAYZ-8009 was shown to enable noninvasive detection of HCC. This retrospective analysis evaluates the correlation between tumor uptake of [<sup>68</sup>Ga]Ga-RAYZ-8009 PET/CT and glypican-3 expression, as determined by immunohistochemistry. <b>Methods:</b> [<sup>68</sup>Ga]Ga-RAYZ-8009 PET/CT scans of 14 patients with histologically confirmed HCC were analyzed. Tracer uptake by HCC lesions was quantified by SUV<sub>max</sub> and SUV<sub>mean</sub> Glypican-3 expression was assessed by immunohistochemistry using the semiquantitative <i>H</i>-score. Correlations between PET/CT uptake and <i>H</i>-score were analyzed using Spearman rank correlation. <b>Results:</b> Of the 14 HCC lesions analyzed, 13 were visually positive on PET, with an SUV<sub>mean</sub> ranging from 1.9 to 63.7 (median, 7.1) and SUV<sub>max</sub> 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 (SUV<sub>mean</sub>: ρ = 0.72, <i>P</i> = 0.0048; SUV<sub>max</sub>: ρ = 0.71, <i>P</i> = 0.0058). <b>Conclusion:</b> [<sup>68</sup>Ga]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.