Abstract 928: Glypican-3 targeted thorium-227 alpha therapy reduces tumor burden in an orthotopic xenograft model of hepatocellular carcinoma

2021 ◽  
Author(s):  
Kevin P. Labadie ◽  
Donald K. Hamlin ◽  
Aimee Kenoyer ◽  
Sara K. Daniel ◽  
Alan F. Utria ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Xenograft Model ◽  
Tumor Burden ◽  
Orthotopic Xenograft ◽  
Orthotopic Xenograft Model ◽  
Alpha Therapy

Yttrium-90-Labeled Anti-Glypican-3 Antibody Reduces Tumor Growth in an Orthotopic Xenograft Model of Hepatocellular Carcinoma

2017 ◽  
Vol 152 (5) ◽  
pp. S1236-S1237
Author(s):  
Andrew D. Ludwig ◽  
Yongwoo D. Seo ◽  
Donald K. Hamlin ◽  
Holly M. Nguyen ◽  
Matthew M. Yeh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Xenograft Model ◽  
Orthotopic Xenograft ◽  
Orthotopic Xenograft Model ◽  
Yttrium 90

scholarly journals Glypican-3 targeted delivery of 89Zr and 90Y as a theranostic radionuclide platform for hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kevin P. Labadie ◽  
Andrew D. Ludwig ◽  
Adrienne L. Lehnert ◽  
Donald K. Hamlin ◽  
Aimee L. Kenoyer ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Targeted Delivery ◽  
Imaging System ◽  
Statistical Significance ◽  
Xenograft Model ◽  
Small Animal ◽  
Preclinical Study ◽  
Tumor Burden ◽  
Orthotopic Xenograft Model ◽  
Positron Emission

AbstractGlypican-3 (GPC3) is a tumor associated antigen expressed by hepatocellular carcinoma (HCC) cells. This preclinical study evaluated the efficacy of a theranostic platform using a GPC3-targeting antibody αGPC3 conjugated to zirconium-89 (89Zr) and yttrium-90 (90Y) to identify, treat, and assess treatment response in a murine model of HCC. A murine orthotopic xenograft model of HCC was generated. Animals were injected with 89Zr-labeled αGPC3 and imaged with a small-animal positron emission/computerized tomography (PET/CT) imaging system (immuno-PET) before and 30 days after radioimmunotherapy (RIT) with 90Y-labeled αGPC3. Serum alpha fetoprotein (AFP), a marker of tumor burden, was measured. Gross tumor volume (GTV) and SUVmax by immuno-PET was measured using fixed intensity threshold and manual segmentation methods. Immuno-PET GTV measurements reliably quantified tumor burden prior to RIT, strongly correlating with serum AFP (R2 = 0.90). Serum AFP was significantly lower 30 days after RIT in 90Y-αGPC3 treated animals compared to those untreated (p = 0.01) or treated with non-radiolabeled αGPC3 (p = 0.02). Immuno-PET GTV measurements strongly correlated with tumor burden after RIT (R2 = 0.87), and GTV of animals treated with 90Y-αGPC3 was lower than in animals who did not receive treatment or were treated with non-radiolabeled αGPC3, although this only trended toward statistical significance. A theranostic platform utilizing GPC3 targeted 89Zr and 90Y effectively imaged, treated, and assessed response after radioimmunotherapy in a GPC3-expressing HCC xenograft model.

Glypican-3 targeted thorium-227 alpha therapy reduces tumor burden in an orthotopic xenograft murine model of hepatocellular carcinoma

2021 ◽  
pp. jnumed.121.262562
Author(s):  
Kevin P Labadie ◽  
Donald K Hamlin ◽  
Aimee Kenoyer ◽  
Sara K Daniel ◽  
Alan F Utria ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Murine Model ◽  
Tumor Burden ◽  
Orthotopic Xenograft ◽  
Alpha Therapy

Effect of the orally available MET inhibitor PF-2341066 on tumor burden and metastasis in an orthotopic xenograft model of bladder cancer.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 263-263
Author(s):  
M. Sorbellini ◽  
A. Giubellino ◽  
G. Srivastava ◽  
C. Sourbier ◽  
P. A. Pinto ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Transitional Cell ◽  
Xenograft Model ◽  
Tumor Burden ◽  
Orthotopic Xenograft ◽  
Orthotopic Xenograft Model ◽  
Reduce Tumor Burden ◽  
Met Inhibitor ◽  
Metastatic Sites ◽  
Nih 3T3

263 Background: Met over-expression has been found in bladder cancer (CaB). However, to date, the effects of Met inhibition in CaB have not been reported. We used a small, orally available, highly specific Met-inhibitor currently on phase 2 clinical trials, to assess its effects in an orthotopic xenograft model of bladder transitional cell carcinoma (TCC). Methods: An orthotopic xenograft murine model of TCC of the bladder was developed with T24-Luciferase positive bladder cancer cells. NIH 3T3 cells producing human hepatocyte growth factor (hHGF) were implanted subcutaneously in mice to provide a source of hHGF. Animals were treated with the selective Met inhibitor (PF-2341066) intra-peritoneally after positive detection of bladder tumor primary and/or metatastatic disease. Fluorescence imaging (Xenogen IVIS) of mice was performed weekly. Mice were euthanized 4 weeks after the start of treatment and their tissues studied histologically. Results: PF-2341066 was found to reduce tumor burden to below detectable levels in both primary and metastatic sites in all mice treated. No noticeable side effects were detected in treated mice secondary to drug administration. Conclusions: This study is the first to test a small orally available Met-selective inhibitor in an orthotopic, HGF-driven model of human CaB. Our results demonstrate that Met-inhibition by PF-2341066 reduces TCC tumor burden supporting its potential use in patients with bladder cancer. No significant financial relationships to disclose.

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