2014
DOI: 10.2967/jnumed.114.145102
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Glypican-3–Targeting F(ab′)2 for 89Zr PET of Hepatocellular Carcinoma

Abstract: Hepatocellular carcinoma (HCC) is an increasingly lethal malignancy for which management is critically dependent on accurate imaging. Glypican-3 (GPC3) is a cell surface receptor overexpressed in most HCCs and provides a unique target for molecular diagnostics. The use of monoclonal antibodies (mAbs) that target GPC3 (αGPC3) in PET imaging has shown promise but comes with inherent limitations associated with mAbs such as long circulation times. This study used 89Zr-conjugated F(ab′)2 fragments directed against… Show more

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Cited by 52 publications
(44 citation statements)
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“…created the GPC3-F(ab ′ )2 fragment and conjugated it to89 Zr; the resultant GPC3-F(ab ′ )2-89 Zr probe showed specific HCC tumor-binding with a 11-h half-life, as compared with approximately 115 h for traditionally used mAb controls 115. This shorter half-life enabled clear tumor visualization in PET at 4 h after probe administration.…”
mentioning
confidence: 99%
“…created the GPC3-F(ab ′ )2 fragment and conjugated it to89 Zr; the resultant GPC3-F(ab ′ )2-89 Zr probe showed specific HCC tumor-binding with a 11-h half-life, as compared with approximately 115 h for traditionally used mAb controls 115. This shorter half-life enabled clear tumor visualization in PET at 4 h after probe administration.…”
mentioning
confidence: 99%
“…Since only about half of HCCs take up 18 FDG PET, the standard functional tracer, immunoPET may serve as an informative imaging biomarker in such circumstances and could allow more timely local or systemic interventions (5). GPC3 is a known marker of HCC and several GPC3-directed agents, including vaccines, monoclonal antibodies, bispecific T-cell engagers, single-domain antibody conjugates, targeted peptides, and chimeric antigen receptor T-cells (26,28,30,(35)(36)(37)(38)(39). Accordingly, identifying tumors that express GPC3 with immunoPET could help better enrich for populations that may most benefit from these treatments (32).…”
Section: Discussionmentioning
confidence: 99%
“…GPC3-derived peptide vaccines, antibodies and their fragments targeting GPC3 have shown promising biological activity and target engagement in vivo, further underscoring the utility of GPC3 as a valuable target in HCC. However, most studies have used murine antibodies, limiting the potential for human translation (26)(27)(28)(29)(30). TAB-H14 is a full-length humanized IgG1 antibody with specificity to GPC3.…”
Section: Introductionmentioning
confidence: 99%
“…Herein, we therefore performed the preclinical evaluation of gal-3 immunotargeting with 89 Zr-DFO-aGal3-F(ab9) 2 for detection of malignant thyroid nodules. F(ab) 2 fragments were used because of their faster blood clearance and lower liver uptake than monoclonal antibodies (6,19,25).…”
Section: Discussionmentioning
confidence: 99%