Abstract | UNLABELLED: METHODS: (125)I-Labeled BLyS protein (50 micro g/kg, 0.185-0.37 MBq per mouse) was injected intravenously into BALB/c mice, and biodistribution was measured by direct counting of radioactivity in dissected tissues and by quantitative whole-body autoradiography (QWBA). RESULTS: The half-life of radiolabeled BLyS protein in blood was approximately 2.7 h in both normal and tumor-bearing mice. The spleen showed the highest uptake of BLyS protein in both normal and tumor-bearing mice, with a maximum concentration (C(max)) of 35-45 percentage injected dose per gram (%ID/g) occurring between 1 and 3 h after injection. In lymph nodes, C(max) was approximately 20 %ID/g in normal and J558 tumor-bearing mice and 8-15 %ID/g in BCL1 tumor-bearing mice. Limited biodistribution data from the J558 tumors showed a C(max) of approximately 15 %ID/g. By contrast, C(max) was only approximately 5 %ID/g for both kidney and liver. QWBA confirmed high radioactivity in spleen, lymph nodes, and stomach contents and low radioactivity in kidney and liver. After 24 h, spleen and lymph nodes were still positive in QWBA images, whereas liver and kidney no longer had observable levels. CONCLUSION: Radiolabeled BLyS showed specific and rapid targeting to lymphoid tissues and B cell tumors in mice. Unlike monoclonal antibodies, which have long plasma half-lives and considerable liver uptake, BLyS has distinct pharmacokinetic and biodistribution properties that may offer advantages compared with antibody-based radioimmunotherapy.
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Authors | Todd A Riccobene, Renée C Miceli, Clint Lincoln, Yvonne Knight, Joseph Meadows, Michael G Stabin, Cynthia Sung |
Journal | Journal of nuclear medicine : official publication, Society of Nuclear Medicine
(J Nucl Med)
Vol. 44
Issue 3
Pg. 422-33
(Mar 2003)
ISSN: 0161-5505 [Print] United States |
PMID | 12621010
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- B-Cell Activating Factor
- B-Cell Activation Factor Receptor
- BLyS receptor
- Iodine Radioisotopes
- Membrane Proteins
- Receptors, Tumor Necrosis Factor
- Recombinant Proteins
- TNFSF13B protein, human
- Tnfrsf13c protein, mouse
- Tnfsf13b protein, mouse
- Tumor Necrosis Factor-alpha
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Topics |
- Animals
- Autoradiography
- B-Cell Activating Factor
- B-Cell Activation Factor Receptor
- Female
- Injections, Intravenous
- Iodine Radioisotopes
(administration & dosage, pharmacology, therapeutic use)
- Lymphoid Tissue
(metabolism)
- Lymphoma, B-Cell
(metabolism, radiotherapy)
- Membrane Proteins
(administration & dosage, pharmacology, therapeutic use)
- Mice
- Mice, Inbred BALB C
- Neoplasm Transplantation
- Plasmacytoma
(metabolism, radiotherapy)
- Radioimmunotherapy
- Radiotherapy Dosage
- Receptors, Tumor Necrosis Factor
(analysis)
- Recombinant Proteins
(administration & dosage, pharmacokinetics, therapeutic use)
- Spleen
(chemistry)
- Tissue Distribution
- Tumor Necrosis Factor-alpha
(administration & dosage, pharmacology, therapeutic use)
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