1. Academic Validation
  2. I-124 codrituzumab imaging and biodistribution in patients with hepatocellular carcinoma

I-124 codrituzumab imaging and biodistribution in patients with hepatocellular carcinoma

  • EJNMMI Res. 2018 Mar 5;8(1):20. doi: 10.1186/s13550-018-0374-8.
Jorge A Carrasquillo 1 Joseph A O'Donoghue 2 Volkan Beylergil 3 Shutian Ruan 3 Neeta Pandit-Taskar 3 Steven M Larson 3 Peter M Smith-Jones 3 4 5 Serge K Lyashchenko 3 Norihisa Ohishi 6 Toshihiko Ohtomo 6 Ghassan K Abou-Alfa 7
Affiliations

Affiliations

  • 1 Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. carrasj1@mskcc.org.
  • 2 Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
  • 3 Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
  • 4 Department of Psychiatry and Behavioral Science, Stony Brook University Hospital, 101 Nicolls Road, Stony Brook, NY, 11794, USA.
  • 5 Department of Radiology, Stony Brook University Hospital, 101 Nicolls Road, Stony Brook, NY, 11794, USA.
  • 6 Chugai Pharmaceutical Co., Ltd., 1-1 Nihonbashi-Muromachi 2-Chome Chuo-ku, Tokyo, 103-8324, Japan.
  • 7 Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
Abstract

Background: I-124 codrituzumab (aka GC33), an antibody directed at Glypican 3, was evaluated in patients with hepatocellular carcinoma (HCC). Fourteen patients with HCC underwent baseline imaging with I-124 codrituzumab (~ 185 MBq, 10 mg). Seven of these patients undergoing sorafenib/immunotherapy with 2.5 or 5 mg/kg of cold codrituzumab had repeat imaging, with co-infusion of I-124 codrituzumab, as part of their immunotherapy treatment. Three patients who progressed while on sorafenib/immunotherapy were re-imaged after a 4-week washout period to assess for the presence of antigen. Serial positron emission tomography (PET) imaging and pharmacokinetics were performed following I-124 codrituzumab. An ELISA assay was used to determine "cold" codrituzumab serum pharmacokinetics and compare it to that of I-124 codrituzumab. Correlation of imaging results was performed with IHC. Short-term safety assessment was also evaluated.

Results: Thirteen patients had tumor localization on baseline I-124 codrituzumab; heterogeneity in tumor uptake was noted. In three patients undergoing repeat imaging while on immunotherapy/sorafenib, evidence of decreased I-124 codrituzumab uptake was noted. All three patients who underwent imaging after progression while on immunotherapy continued to have I-124 codrituzumab tumor uptake. Pharmacokinetics of I-124 codrituzumab was similar to that of other intact IgG. No significant adverse events were observed related to the I-124 codrituzumab.

Conclusions: I-124 codrituzumab detected tumor localization in most patients with HCC. Pharmacokinetics was similar to that of other intact iodinated humanized IgG. No visible cross-reactivity with normal organs was observed.

Keywords

Antibody; Codrituzumab; Glypican; Hepatocellular; I-124.

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