Abstract | BACKGROUND: 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.
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Authors | Sui Shen, Andres Forero, Ruby F Meredith, Albert F LoBuglio |
Journal | Cancer biotherapy & radiopharmaceuticals
(Cancer Biother Radiopharm)
Vol. 26
Issue 1
Pg. 127-33
(Feb 2011)
ISSN: 1557-8852 [Electronic] United States |
PMID | 21355784
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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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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