Optimizing the sequence of combination therapy with radiolabeled antibodies and fractionated external beam Journal Article
| Authors: | Ruan, S.; O'Donoghue, J. A.; Larson, S. M.; Finn, R. D.; Jungbluth, A.; Welt, S.; Humm, J. L. |
| Article Title: | Optimizing the sequence of combination therapy with radiolabeled antibodies and fractionated external beam |
| Abstract: | The purpose of this study was to determine the optimum sequence for combined modality therapy with radiolabeled antibodies and fractionated external beam radiation. Methods: The uptake and distribution of a nontherapeutic activity of 125I-labeled tumor-associated A33 monoclonal antibody was determined in SW1222 human colon carcinoma xenografts in nude mice for 4 study groups: group 1, radiolabeled antibody alone; group 2, radiolabeled antibody administered (day 0) immediately before the first of 5 daily fractions of 2-Gy, 320-kilovolt peak x-rays; group 3, radiolabeled antibody administered after the fifth radiation fraction (day 5); and group 4, radiolabeled antibody administered 5 d after irradiation (day 10). Tumors were excised 5 d after antibody administration. Tumors were frozen and sectioned for histology and phosphor plate autoradiography. The percentage of A33 antigen-expressing cells was estimated by immunohistochemical staining. Results: The average tumor uptake values relative to control group 1 were 1.47 (group 2), 0.78 (group 3), and 0.21 (group 4), which illustrates that tumor uptake is increased by almost 50% when the antibody is present in the blood at the start of irradiation. Five days into a fractionated irradiation protocol, antibody uptake was reduced, falling more significantly on day 10. Phosphor plate autoradiographs showed decreased uptake uniformity for groups 3 and 4. Immunohistochemical data showed a reduction in A33 antigen-positive cells from 85%, 64%, 50%, to 41% for groups 1-4, respectively. Conclusion: Maximum radiolabeled antibody tumor uptake was achieved when the antibody was administered just before radiation therapy. This might be explained by a transient increase in capillary leakage to macromolecules, followed by a reduction at later times, possibly the result of capillary damage and occlusion. |
| Keywords: | immunohistochemistry; controlled study; human cell; nonhuman; mouse; animals; mice; animal tissue; radiotherapy dosage; animal experiment; animal model; tumor cells, cultured; colorectal neoplasms; antibodies, monoclonal; antigens; drug uptake; isotope labeling; xenograft; nude mouse; mice, nude; radiation dose fractionation; radiation therapy; neoplasm transplantation; colon carcinoma; dose fractionation; radioimmunotherapy; autoradiography; antibody labeling; a33 antibody; cancer graft; human; priority journal; article; phosphor plate autoradiography; monoclonal antibody i 125 |
| Journal Title: | Journal of Nuclear Medicine |
| Volume: | 41 |
| Issue: | 11 |
| ISSN: | 0161-5505 |
| Publisher: | Society of Nuclear Medicine |
| Date Published: | 2000-11-01 |
| Start Page: | 1905 |
| End Page: | 1912 |
| Language: | English |
| PUBMED: | 11079503 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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