title: Glypican-3-targeted 89Zr PET imaging of hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is a devastating malignancy in which imperfect imaging plays a primary role in diagnosis. Glypican-3 (GPC3) is an HCC-specific cell surface proteoglycan overexpressed in most HCCs. This paper presents the use of (89)Zr-conjugated monoclonal antibody against GPC3 ((89)Zr-αGPC3) for intrahepatic tumor localization using PET.
  
  
  METHODS
  Polymerase chain reaction confirmed relative GPC3 expression in cell lines. In vitro binding, in vivo biodistribution, and small-animal PET studies were performed on GPC3-expressing HepG2 and non-GPC3-expressing HLF and RH7777 cells and orthotopic xenografts.
  
  
  RESULTS
  (89)Zr-αGPC3 demonstrated antibody-dependent, antigen-specific tumor binding. HepG2 liver tumors exhibited high peak uptake (836.6 ± 86.6 percentage injected dose [%ID]/g) compared with background liver (27.5 ± 1.6 %ID/g). Tumor-to-liver contrast ratio was high and peaked at 32.5. The smallest HepG2 tumor (<1 mm) showed lower peak uptake (42.5 ± 6.4 %ID/g) and tumor-to-liver contrast (1.57) but was still clearly visible on PET. Day 7 tissue activity was still substantial in HepG2 tumors (466.4 ± 87.6 %ID/g) compared with control RH7777 tumors (3.9 ± 1.3 %ID/g, P < 0.01), indicating antigen specificity by (89)Zr-αGPC3. HepG2 tumor treated with unlabeled αGPC3 or heat-denatured (89)Zr-αGPC3 demonstrated tumor activity (2.1 %ID/g) comparable to that of control xenografts, confirming antibody dependency.
  
  
  CONCLUSIONS
  This study demonstrated the feasibility of using (89)Zr-αGPC3 to image HCC in the liver, as well as the qualitative determination of GPC3 expression via small-animal PET. The ability to clarify the identity of small liver lesions with an HCC-specific PET probe would provide clinicians with vital information that could significantly alter patient management, warranting further investigation for clinical translation.
authors.affiliation: Department of Surgery, University of Washington, Seattle, Washington.
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Sham
authors.forename: Forrest M
authors.initials: FM
authors.lastname: Kievit
authors.forename: John R
authors.initials: JR
authors.lastname: Grierson
authors.forename: Robert S
authors.initials: RS
authors.lastname: Miyaoka
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Yeh
authors.forename: Miqin
authors.initials: M
authors.lastname: Zhang
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Yeung
authors.forename: Satoshi
authors.initials: S
authors.lastname: Minoshima
authors.forename: James O
authors.initials: JO
authors.lastname: Park
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging*; D045744:Cell Line, Tumor; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053673:Glypicans / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D007797:Laminin / Q000737:chemistry; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000000981:diagnostic imaging*; D051379:Mice; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography; D011509:Proteoglycans / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D014018:Tissue Distribution; D015040:Zirconium
chemical_list: D000911:Antibodies, Monoclonal; D004338:Drug Combinations; D053673:Glypicans; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C059485:matrigel; D003094:Collagen; D015040:Zirconium
keywords: 89Zr; PET; glypican 3; hepatocellular carcinoma; liver