A peptide binder to Glypican-3 (GPC3), RAYZ-8009, was developed as a theranostic agent for hepatocellular carcinoma (HCC). RAYZ-8009 is a macrocyclic peptide that binds to GPC3 with high affinity and specificity, and can be labeled with various radioisotopes such as ¹⁷⁷Lu and ²²⁵Ac. It showed high binding affinity to GPC3 in human, mouse, canine, and cynomolgus monkey tissues, and no binding to other glypican family members. RAYZ-8009 demonstrated efficient internalization in GPC3-positive HepG2 cells and showed sustained tumor uptake with fast renal clearance in vivo. Biodistribution studies showed that ¹⁷⁷Lu-RAYZ-8009 had high tumor-to-kidney ratios and minimal uptake in normal tissues. RAYZ-8009 showed significant and durable tumor regression and survival benefit when used as a single agent or in combination with lenvatinib in GPC3-positive HCC xenografts. The study also demonstrated that RAYZ-8009 could be used for both diagnostic and therapeutic purposes, making it a promising theranostic agent for HCC. GPC3 is a membrane-associated glycoprotein that is significantly upregulated in HCC and is minimally expressed in normal tissues, making it an attractive target for targeted radiotherapy. RAYZ-8009 is a potent and selective GPC3-targeted radiopharmaceutical that shows promise for the treatment of GPC3-positive HCC.A peptide binder to Glypican-3 (GPC3), RAYZ-8009, was developed as a theranostic agent for hepatocellular carcinoma (HCC). RAYZ-8009 is a macrocyclic peptide that binds to GPC3 with high affinity and specificity, and can be labeled with various radioisotopes such as ¹⁷⁷Lu and ²²⁵Ac. It showed high binding affinity to GPC3 in human, mouse, canine, and cynomolgus monkey tissues, and no binding to other glypican family members. RAYZ-8009 demonstrated efficient internalization in GPC3-positive HepG2 cells and showed sustained tumor uptake with fast renal clearance in vivo. Biodistribution studies showed that ¹⁷⁷Lu-RAYZ-8009 had high tumor-to-kidney ratios and minimal uptake in normal tissues. RAYZ-8009 showed significant and durable tumor regression and survival benefit when used as a single agent or in combination with lenvatinib in GPC3-positive HCC xenografts. The study also demonstrated that RAYZ-8009 could be used for both diagnostic and therapeutic purposes, making it a promising theranostic agent for HCC. GPC3 is a membrane-associated glycoprotein that is significantly upregulated in HCC and is minimally expressed in normal tissues, making it an attractive target for targeted radiotherapy. RAYZ-8009 is a potent and selective GPC3-targeted radiopharmaceutical that shows promise for the treatment of GPC3-positive HCC.