Glypican-3–Targeted <sup>89</sup>Zr PET Imaging of Hepatocellular Carcinoma: Where Antibody Imaging Dares to Tread

Marquez, Bernadette V.; Zheleznyak, Alexander; Lapi, Suzanne E.

doi:10.2967/jnumed.113.136234

Cited by 4 publications

(2 citation statements)

References 25 publications

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“…Radiotracer synthesis and targeted molecular imaging modalities, such as immuno-PET, have already become the focus of current research, and their diagnostic capacity for smaller HCC lesions is encouraging. However, most research about radiotracers and immuno-PET is performed on experimental animals, and immuno-PET also shows the overexpression of molecular targets in many non-liver malignancies[79,88]. Further evaluation of their immune reactivity is needed, and clinical translation requires more evidence.…”

Section: Resultsmentioning

confidence: 99%

Positron-emission tomography for hepatocellular carcinoma: Current status and future prospects

Rencai¹,

She²,

Gao³

et al. 2019

WJG

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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality worldwide. Various imaging modalities provide important information about HCC for its clinical management. Since positron-emission tomography (PET) or PET-computed tomography was introduced to the oncologic setting, it has played crucial roles in detecting, distinguishing, accurately staging, and evaluating local, residual, and recurrent HCC. PET imaging visualizes tissue metabolic information that is closely associated with treatment. Dynamic PET imaging and dual-tracer have emerged as complementary techniques that aid in various aspects of HCC diagnosis. The advent of new radiotracers and the development of immuno-PET and PET-magnetic resonance imaging have improved the ability to detect lesions and have made great progress in treatment surveillance. The current PET diagnostic capabilities for HCC and the supplementary techniques are reviewed herein.

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Section: Resultsmentioning

confidence: 99%

Positron-emission tomography for hepatocellular carcinoma: Current status and future prospects

Rencai¹,

She²,

Gao³

et al. 2019

WJG

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“…Despite this lower absolute tumor uptake, 89 Zr-αGPC3-F(ab′)2 was still able to achieve a high tumor-to-liver ratio (23.3) at 4 h because of low background blood and liver activity. This tumor-to-background ratio is still superior to most whole-antibody-targeted PET probes, with peak signal-to-background ratios in the 1.5–4 range (37). It was also a prestudy consideration that the smaller size of 89 Zr-αGPC3-F(ab′)2 would lead to increased susceptibility to the effects of enhanced permeability retention in tumors and therefore increased nonspecific binding.…”

Section: Discussionmentioning

confidence: 99%

Glypican-3–Targeting F(ab′)2 for ⁸⁹Zr PET of Hepatocellular Carcinoma

et al. 2014

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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 GPC3 (89Zr-αGPC3-F(ab′)2) to evaluate the feasibility of the fragments as a diagnostic immuno-PET imaging probe. Methods Immobilized ficin was used to digest αGPC3, creating αGPC3-F(ab′)2 fragments subsequently conjugated to 89Zr. In vivo biodistribution and PET studies were performed on GPC3-expressing HepG2 and GPC3-nonexpressing RH7777 orthotopic xenografts. Results Reliable αGPC3-F(ab′)2 production via immobilized ficin digestion was verified by high-performance liquid chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis. 89Zr-αGPC3-F(ab′)2 demonstrated F(ab′)2-dependent, antigen-specific cell binding. HepG2 tumor uptake was higher than any other tissue, peaking at 100 ± 21 percentage injected dose per gram (%ID/g) 24 h after injection, a value 33- to 38-fold higher than GPC3-nonexpressing RH7777 tumors. The blood half-life of the 89Zr-αGPC3-F(ab′)2 conjugate was approximately 11 h, compared with approximately 115 h for historic mAb controls. This shorter half-life enabled clear tumor visualization on PET 4 h after administration, with a resultant peak tumor-to-liver contrast ratio of 23.3. Blocking antigen-expressing tumors with an excess of nonradiolabeled αGPC3 resulted in decreased tumor uptake similar to native liver. The kidneys exhibited high tissue uptake, peaking at 24 h with 83 ± 12 %ID/g. HepG2 tumors ranging from 1.5 to 7 mm were clearly visible on PET, whereas larger RH7777 tumors displayed signal lower than background liver tissue. Conclusion This study demonstrates the feasibility of using 89Zr-αGPC3-F(ab′) 2 for intrahepatic tumor localization with small-animal PET. Faster blood clearance and lower background liver uptake enable excellent signal-to-noise ratios at early time points. Increased renal uptake is similar to that as has been seen with clinical radioactive peptide imaging. 89Zr-αGPC3-F(ab′)2 addresses some of the shortcomings of whole-antibody immuno-PET probes. Further optimization is warranted to maximize probe sensitivity and specificity in the process of clinical translation.

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Recent Advances of Radionuclide-Based Molecular Imaging of Atherosclerosis

Kazuma¹,

Sultan²,

Zhao³

et al. 2015

CPD

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Atherosclerosis is a systemic disease characterized by the development of multifocal plaque lesions within vessel walls and extending into the vascular lumen. The disease takes decades to develop symptomatic lesions, affording opportunities for accurate detection of plaque progression, analysis of risk factors responsible for clinical events, and planning personalized treatment. Of the available molecular imaging modalities, radionuclide-based imaging strategies have been favored due to their sensitivity, quantitative detection and pathways for translational research. This review summarizes recent advances of radiolabeled small molecules, peptides, antibodies and nanoparticles for atherosclerotic plaque imaging during disease progression.

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Glypican-3–Targeted ⁸⁹Zr PET Imaging of Hepatocellular Carcinoma: Where Antibody Imaging Dares to Tread

Cited by 4 publications

References 25 publications

Positron-emission tomography for hepatocellular carcinoma: Current status and future prospects

Positron-emission tomography for hepatocellular carcinoma: Current status and future prospects

Glypican-3–Targeting F(ab′)2 for ⁸⁹Zr PET of Hepatocellular Carcinoma

Recent Advances of Radionuclide-Based Molecular Imaging of Atherosclerosis

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Glypican-3–Targeted 89Zr PET Imaging of Hepatocellular Carcinoma: Where Antibody Imaging Dares to Tread

Cited by 4 publications

References 25 publications

Positron-emission tomography for hepatocellular carcinoma: Current status and future prospects

Positron-emission tomography for hepatocellular carcinoma: Current status and future prospects

Glypican-3–Targeting F(ab′)2 for 89Zr PET of Hepatocellular Carcinoma

Recent Advances of Radionuclide-Based Molecular Imaging of Atherosclerosis

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Glypican-3–Targeted ⁸⁹Zr PET Imaging of Hepatocellular Carcinoma: Where Antibody Imaging Dares to Tread

Glypican-3–Targeting F(ab′)2 for ⁸⁹Zr PET of Hepatocellular Carcinoma