Clearance kinetics and external dosimetry of (131)I-labeled murine and humanized monoclonal antibody A33 in patients with colon cancer: Radiation safety implications Journal Article
| Authors: | Dauer, L. T.; Boylan, D. C.; Williamson, M. J.; St. Germain, J.; Larson, S. M. |
| Article Title: | Clearance kinetics and external dosimetry of (131)I-labeled murine and humanized monoclonal antibody A33 in patients with colon cancer: Radiation safety implications |
| Abstract: | The monoclonal antibody (mAb) A33 detects a membrane antigen that is expressed on greater than 95% of metastatic human colorectal cancers. Previous studies have shown excellent tumor-targeting of I-labeled murine and humanized forms of the mAb. A retrospective analysis of whole-body clearance in the murine form was performed for comparison to the humanized form. Serial whole-body dose rate measurements were obtained for 55 treatments on 30 patients participating in phase I/II dose escalation studies of therapeutic I-murine A33 mAb. Whole-body retention fractions over time were derived. Each treatment was fit with exponential curves to determine the effective half-lives and corresponding clearance fractions. There was a large variability in the calculated mono-exponential clearance effective half-life time, with a mean value of 36.5 h ± 8.5 h. A bi-exponential fit of all combined data shows that 60% of the administered dose rapidly clears with a biological half-time of 23.9 h and 40% clears with a slower biological half-time of 101.2 h. The whole-body clearance proved to be more rapid in the murine form when compared with recent studies on the humanized form of radiolabeled A33 mAb. The variability in whole-body clearance reinforces the need for patient-specific tracer dosimetry for clinical care and radiation safety precautions. In addition, the slower clearance of the humanized form of the A33 mAb requires longer term radiation safety precautions than the earlier murine form. As other monoclonal antibodies progress from murine to humanized forms, radiopharmacokinetics should be evaluated for clinical and radiation safety implications. ©2009Health Physics Society. |
| Keywords: | adult; clinical article; aged; aged, 80 and over; middle aged; retrospective studies; unclassified drug; nonhuman; cancer patient; radiation dose; mouse; metabolism; phase 2 clinical trial; radiotherapy dosage; colonic neoplasms; retrospective study; tumor antigen; monoclonal antibody; patient care; immunology; antibodies, monoclonal; antigens, neoplasm; iodine 131; radioactive iodine; drug distribution; drug retention; tissue distribution; iodine radioisotopes; dosimetry; radiation dose fractionation; membrane glycoproteins; colon cancer; colon tumor; membrane protein; murinae; drug clearance; metabolic clearance rate; relative biological effectiveness; phase 1 clinical trial; drug half life; <sup>131</sup>i; biokinetics; medical radiation; monoclonal antibody a33 i 131; gpa33 protein, mouse; half life time; radiation safety; body burden; radioimmunotherapy; relative biologic effectiveness; whole body counting; clinical trials, phase i as topic; clinical trials, phase ii as topic; whole-body counting |
| Journal Title: | Health Physics |
| Volume: | 96 |
| Issue: | 5 |
| ISSN: | 0017-9078 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2009-05-01 |
| Start Page: | 550 |
| End Page: | 557 |
| Language: | English |
| DOI: | 10.1097/01.HP.0000342831.26198.eb |
| PUBMED: | 19359848 |
| PROVIDER: | scopus |
| PMCID: | PMC4045026 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 30 November 2010" - "CODEN: HLTPA" - "Source: Scopus" |
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