Abstract | UNLABELLED: METHODS: RESULTS: None of the unconjugated antibodies was effective against established and rapidly growing xenografts, but PT-RAIT, at approximately 30% of its maximum tolerated dose, and radioimmunotherapy alone, at its maximum tolerated dose, were able to arrest growth and even entirely ablate tumors in some animals. Only combinations with veltuzumab improved therapeutic responses, most significantly when a veltuzumab regimen (weekly, 1.0 mg followed by 3 x 0.5 mg) was initiated 1 wk after PT-RAIT or (90)Y-veltuzumab. Biodistribution data indicated that when unlabeled veltuzumab (1.0 or 0.25 mg) was administered in advance of the radiolabeled veltuzumab or bispecific antibody injection, tumor uptake was significantly reduced ((111)In- veltuzumab, 47% and 25%, respectively; (111)In- hapten- peptide, 74% and 49%, respectively). Despite an approximately 50% decrease in radioactivity uptake in the tumor, antitumor responses were not diminished significantly for (90)Y-veltuzumab, and in the case of PT-RAIT responses were improved. However, higher amounts of predosed veltuzumab reduced the effects of PT-RAIT. CONCLUSION: These studies suggest that administering unlabeled anti-CD20 IgG therapy after the radioactivity dose provides the best efficacy and that the amount of unlabeled anti-CD20 IgG administered as a predose to anti-CD20-targeted radionuclide therapy should be minimized.
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Authors | Robert M Sharkey, Habibe Karacay, Christine R Johnson, Samuel Litwin, Edmund A Rossi, William J McBride, Chien-Hsing Chang, David M Goldenberg |
Journal | Journal of nuclear medicine : official publication, Society of Nuclear Medicine
(J Nucl Med)
Vol. 50
Issue 3
Pg. 444-53
(Mar 2009)
ISSN: 0161-5505 [Print] United States |
PMID | 19223402
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Antibodies, Bispecific
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antigens, CD20
- Antigens, Differentiation, B-Lymphocyte
- Histocompatibility Antigens Class II
- Indium Radioisotopes
- Radiopharmaceuticals
- Sialic Acid Binding Ig-like Lectin 2
- Yttrium Radioisotopes
- invariant chain
- epratuzumab
- veltuzumab
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Topics |
- Animals
- Antibodies, Bispecific
(administration & dosage, immunology, therapeutic use)
- Antibodies, Monoclonal
(administration & dosage, therapeutic use)
- Antibodies, Monoclonal, Humanized
- Antigens, CD20
(immunology)
- Antigens, Differentiation, B-Lymphocyte
(immunology)
- Burkitt Lymphoma
(metabolism, radiotherapy)
- Drug Therapy, Combination
- Histocompatibility Antigens Class II
(immunology)
- Humans
- Indium Radioisotopes
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Neoplasm Transplantation
- Radioimmunotherapy
- Radiopharmaceuticals
(administration & dosage, therapeutic use)
- Sialic Acid Binding Ig-like Lectin 2
(immunology)
- Transplantation, Heterologous
- Yttrium Radioisotopes
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