Glypican-3-targeted 89zr PEt imaging of hepatocellular carcinoma

Jonathan G. Sham, Forrest M Kievit, John R. Grierson, Robert S. Miyaoka, Matthew M. Yeh, Miqin Zhang, Raymond S. Yeung, Satoshi Minoshima, James O. Park

Research output: Contribution to journalArticle

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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 89Zr-conjugated monoclonal antibody against GPC3 (89Zr-aGPC3) 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-aGPC3 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-aGPC3. HepG2 tumor treated with unlabeled aGPC3 or heat-denatured 89Zr-aGPC3 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-aGPC3 to image HCC in the liver, as well as the qualitative determination of GPC3 expression via smallanimal 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.

Original languageEnglish (US)
Pages (from-to)799-804
Number of pages6
JournalJournal of Nuclear Medicine
Volume55
Issue number5
DOIs
StatePublished - May 1 2014

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Glypicans
Hepatocellular Carcinoma
Neoplasms
Monoclonal Antibodies
Liver
Heterografts
Antibodies
Feasibility Studies
Neoplasm Antigens
Proteoglycans
Hot Temperature

Keywords

  • 89Zr
  • Glypican 3
  • Hepatocellular carcinoma
  • Liver
  • PET

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Sham, J. G., Kievit, F. M., Grierson, J. R., Miyaoka, R. S., Yeh, M. M., Zhang, M., ... Park, J. O. (2014). Glypican-3-targeted 89zr PEt imaging of hepatocellular carcinoma. Journal of Nuclear Medicine, 55(5), 799-804. https://doi.org/10.2967/jnumed.113.132118

Glypican-3-targeted 89zr PEt imaging of hepatocellular carcinoma. / Sham, Jonathan G.; Kievit, Forrest M; Grierson, John R.; Miyaoka, Robert S.; Yeh, Matthew M.; Zhang, Miqin; Yeung, Raymond S.; Minoshima, Satoshi; Park, James O.

In: Journal of Nuclear Medicine, Vol. 55, No. 5, 01.05.2014, p. 799-804.

Research output: Contribution to journalArticle

Sham, JG, Kievit, FM, Grierson, JR, Miyaoka, RS, Yeh, MM, Zhang, M, Yeung, RS, Minoshima, S & Park, JO 2014, 'Glypican-3-targeted 89zr PEt imaging of hepatocellular carcinoma', Journal of Nuclear Medicine, vol. 55, no. 5, pp. 799-804. https://doi.org/10.2967/jnumed.113.132118
Sham, Jonathan G. ; Kievit, Forrest M ; Grierson, John R. ; Miyaoka, Robert S. ; Yeh, Matthew M. ; Zhang, Miqin ; Yeung, Raymond S. ; Minoshima, Satoshi ; Park, James O. / Glypican-3-targeted 89zr PEt imaging of hepatocellular carcinoma. In: Journal of Nuclear Medicine. 2014 ; Vol. 55, No. 5. pp. 799-804.
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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 89Zr-conjugated monoclonal antibody against GPC3 (89Zr-aGPC3) 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-aGPC3 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-aGPC3. HepG2 tumor treated with unlabeled aGPC3 or heat-denatured 89Zr-aGPC3 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-aGPC3 to image HCC in the liver, as well as the qualitative determination of GPC3 expression via smallanimal 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.",
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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-aGPC3) 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-aGPC3 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-aGPC3. HepG2 tumor treated with unlabeled aGPC3 or heat-denatured 89Zr-aGPC3 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-aGPC3 to image HCC in the liver, as well as the qualitative determination of GPC3 expression via smallanimal 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.

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