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Biodistribution and dosimetry of In-111/Y-90-HuCC49ΔCh2 (IDEC-159) in patients with metastatic colorectal adenocarcinoma.

AbstractBACKGROUND:
CC49, an antibody (mAb) reactive to tumor-associated glycoprotein (TAG-72), has been extensively studied for radioimmunotherapy for colon cancer. Myelotoxicity has been dose-limiting because of prolonged circulation time in the plasma, and human anti-mouse antibody responses were observed in the majority of patients. A CH2 domain deleted and humanized CC49 (HuCC49ΔCh2) was developed to ameliorate these problems. This study reports biodistribution and dosimetry of (111)In/(90)Y-HuCC49ΔCh2 (IDEC-159).
MATERIALS AND METHODS:
Five (5) patients with colon cancer were enrolled. Each patient received intravenous administration of 185 MBq (111)In-HuCC49ΔCh2, followed by sequential gamma camera imaging, and blood counting. Uptakes and clearance half-lives for organs and tumors were quantified from images. Absorbed doses for (90)Y-HuCC49ΔCh2 were derived from (111)In-HuCC49ΔCh2 kinetic data.
RESULTS:
Compared to reported (111)In/(90)Y-CC49 data in the literature, median blood circulation T(1/2β) was less at 38 (31-43) hours for (90)Y-HuCC49ΔCh2, than 50 hours for (90)Y-CC49. Median tumor-to-marrow absorbed dose ratio was 18 for (90)Y-HuCC49ΔCh2, and 9.53 for (90)Y-CC49. Median tumor-to-liver absorbed dose ratio was 3.14 for (90)Y-HuCC49ΔCh2, and 1.0 for (90)Y-CC49. Median tumor-to-spleen absorbed dose was 3.19 for (90)Y-HuCC49ΔCh2, and 1.07 for (90)Y-CC49.
CONCLUSIONS:
A humanized and CH2 domain-deleted CC49 antibody radiolabeled with (111)In/(90)Y showed improved tumor-to-normal dose ratios over those reported from studies with intact CC49.
AuthorsSui Shen, Andres Forero, Ruby F Meredith, Albert F LoBuglio
JournalCancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 26 Issue 1 Pg. 127-33 (Feb 2011) ISSN: 1557-8852 [Electronic] United States
PMID21355784 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Neoplasm
  • B72.3 antibody
  • Immunotoxins
  • Indium Radioisotopes
  • Yttrium Radioisotopes
Topics
  • Adenocarcinoma (blood, immunology, metabolism, radiotherapy)
  • Antibodies, Monoclonal (administration & dosage, immunology, pharmacokinetics)
  • Antibodies, Neoplasm (administration & dosage, immunology, metabolism)
  • Colorectal Neoplasms (blood, immunology, metabolism, radiotherapy)
  • Female
  • Humans
  • Immunotoxins (administration & dosage, immunology, pharmacokinetics)
  • Indium Radioisotopes (administration & dosage, blood, pharmacokinetics)
  • Male
  • Radioimmunotherapy (methods)
  • Radiometry (methods)
  • Radionuclide Imaging (methods)
  • Tissue Distribution
  • Yttrium Radioisotopes (administration & dosage, blood, pharmacokinetics)

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