Optimizing the Sequence of Combination Therapy with Radiolabeled Antibodies and Fractionated External Beam

• Published in: The Journal of nuclear medicine (1978) Vol. 41; no. 11; pp. 1905 - 1912
• Main Authors: Ruan, Shutian, O'Donoghue, Joseph A, Larson, Steven M, Finn, Ronald D, Jungbluth, Achim, Welt, Sydney, Humm, John L
• Format: Journal Article
• Language: English
• Published: Reston, VA Soc Nuclear Med 01-11-2000; Society of Nuclear Medicine
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antigens - analysis; Autoradiography; Biological and medical sciences; Colorectal Neoplasms - immunology; Colorectal Neoplasms - pathology; Colorectal Neoplasms - radiotherapy; Diseases of the digestive system; Dose Fractionation; Medical sciences; Mice; Mice, Nude; Miscellaneous; Neoplasm Transplantation; Radioimmunotherapy; Radiotherapy Dosage; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Tumor Cells, Cultured; Immunohistochemistry; Animal model; Associated technique; Maximal dose; Rodentia; Tumoral marker; Malignant tumor; Experimental study; Heterograft; Radiotherapy; Fractionated dose; Colonic disease; Autoradiography; Vertebrata; Mammalia; Mouse; Animal; Immunoradiotherapy; Digestive diseases; Intestinal disease; Colon; Pharmacokinetics
• ISSN: 0161-5505; 1535-5667

The purpose of this study was to determine the optimum sequence for combined modality therapy with radiolabeled antibodies and fractionated external beam radiation.
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.
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.
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.