TY - JOUR T1 - Optimizing the Sequence of Combination Therapy with Radiolabeled Antibodies and Fractionated External Beam JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1905 LP - 1912 VL - 41 IS - 11 AU - Shutian Ruan AU - Joseph A. O'Donoghue AU - Steven M. Larson AU - Ronald D. Finn AU - Achim Jungbluth AU - Sydney Welt AU - John L. Humm Y1 - 2000/11/01 UR - http://jnm.snmjournals.org/content/41/11/1905.abstract N2 - 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. ER -