RT Journal Article SR Electronic T1 Glypican-3–Targeted 89Zr PET Imaging of Hepatocellular Carcinoma JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 799 OP 804 DO 10.2967/jnumed.113.132118 VO 55 IS 5 A1 Jonathan G. Sham A1 Forrest M. Kievit A1 John R. Grierson A1 Robert S. Miyaoka A1 Matthew M. Yeh A1 Miqin Zhang A1 Raymond S. Yeung A1 Satoshi Minoshima A1 James O. Park YR 2014 UL http://jnm.snmjournals.org/content/55/5/799.abstract AB 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 89Zr-conjugated monoclonal antibody against GPC3 (89Zr-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: 89Zr-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 89Zr-αGPC3. HepG2 tumor treated with unlabeled αGPC3 or heat-denatured 89Zr-αGPC3 demonstrated tumor activity (2.1 %ID/g) comparable to that of control xenografts, confirming antibody dependency. Conclusion: This study demonstrated the feasibility of using 89Zr-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.