Journal article
Glypican-3 targeted positron emission tomography detects sub-centimeter tumors in a xenograft model of hepatocellular carcinoma
EJNMMI research, Vol.13(1), pp.35-7
04/27/2023
DOI: 10.1186/s13550-023-00980-9
PMCID: PMC10140215
PMID: 37103671
Abstract
BackgroundEarly intrahepatic recurrence is common after surgical resection of hepatocellular carcinoma (HCC) and leads to increased morbidity and mortality. Insensitive and nonspecific diagnostic imaging contributes to EIR and results in missed treatment opportunities. In addition, novel modalities are needed to identify targets amenable for targeted molecular therapy. In this study, we evaluated a zirconium-89 radiolabeled glypican-3 (GPC3) targeting antibody conjugate (Zr-89-alpha GPC3) for use in positron emission tomography (PET) for detection of small, GPC3(+) HCC in an orthotopic murine model. Athymic nu/J mice received hepG2, a GPC3(+) human HCC cell line, into the hepatic subcapsular space. Tumor-bearing mice were imaged by PET/computerized tomography (CT) 4 days after tail vein injection of Zr-89-alpha GPC3. Livers were then excised for the tumors to be identified, measured, bisected, and then serially sectioned at 500 mu m increments. Sensitivity and specificity of PET/CT for Zr-89-alpha GPC3-avid tumors were assessed using tumor confirmation on histologic sections as the gold standard.ResultsIn tumor-bearing mice, Zr-89-alpha GPC3 avidly accumulated in the tumor within four hours of injection with ongoing accumulation over time. There was minimal off-target deposition and rapid bloodstream clearance. Thirty-eight of 43 animals had an identifiable tumor on histologic analysis. Zr-89-alpha GPC3 immuno-PET detected all 38 histologically confirmed tumors with a sensitivity of 100%, with the smallest tumor detected measuring 330 mu m in diameter. Tumor-to-liver ratios of Zr-89-alpha GPC3 uptake were high, creating excellent spatial resolution for ease of tumor detection on PET/CT. Two of five tumors that were observed on PET/CT were not identified on histologic analysis, yielding a specificity of 60%.Conclusions(89)Zr-alpha GPC3 avidly accumulated in GPC3(+) tumors with minimal off-target sequestration. Zr-89-alpha GPC3 immuno-PET yielded a sensitivity of 100% and detected sub-millimeter tumors. This technology may improve diagnostic sensitivity of small HCC and select GPC3(+) tumors for targeted therapy. Human trials are warranted to assess its impact.
Details
- Title: Subtitle
- Glypican-3 targeted positron emission tomography detects sub-centimeter tumors in a xenograft model of hepatocellular carcinoma
- Creators
- Kevin P. Labadie - University of WashingtonAdrienne L. Lehnert - University of WashingtonAimee L. Kenoyer - Cancer Research CenterDonald K. Hamlin - University of WashingtonAndrew D. Ludwig - University of WashingtonAlan F. Utria - University of WashingtonSara K. Daniel - University of WashingtonTara N. Mihailovic - University of WashingtonAlexander Prossnitz - University of WashingtonJohnnie J. Orozco - Fred Hutch Cancer CenterYawen Li - University of WashingtonD. Scott Wilbur - University of WashingtonRobert S. Miyaoka - University of WashingtonJames O. Park - University of Washington
- Resource Type
- Journal article
- Publication Details
- EJNMMI research, Vol.13(1), pp.35-7
- DOI
- 10.1186/s13550-023-00980-9
- PMID
- 37103671
- PMCID
- PMC10140215
- NLM abbreviation
- EJNMMI Res
- ISSN
- 2191-219X
- eISSN
- 2191-219X
- Publisher
- Springer Nature
- Number of pages
- 7
- Grant note
- 1S10OD010652-01 / NIH Shared Instrumentation Grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 1S10 OD 017980-0; S10 RR024689-01 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30 CA015704 / Translational BioImaging Core (TBIC) Shared Resource of the Fred Hutch/University of Washington Cancer Consortium
- Language
- English
- Date published
- 04/27/2023
- Academic Unit
- Surgery
- Record Identifier
- 9985015819802771
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