Abstract |
Pretargeted radioimmunotherapy ( PRIT) is designed to enhance the directed delivery of radionuclides to malignant cells. Through a series of studies in 19 nonhuman primates (Macaca fascicularis), the potential therapeutic advantage of anti-CD45 PRIT was evaluated. Anti-CD45 PRIT demonstrated a significant improvement in target-to-normal organ ratios of absorbed radiation compared with directly radiolabeled bivalent antibody (conventional radioimmunotherapy [RIT]). Radio- DOTA-biotin administered 48 hours after anti-CD45 streptavidin fusion protein (FP) [BC8 (scFv)(4)SA] produced markedly lower concentrations of radiation in nontarget tissues compared with conventional RIT. PRIT generated superior target:normal organ ratios in the blood, lung, and liver (10.3:1, 18.9:1, and 9.9:1, respectively) compared with the conventional RIT controls (2.6:1, 6.4:1, and 2.9:1, respectively). The FP demonstrated superior retention in target tissues relative to comparable directly radiolabeled bivalent anti-CD45 RIT. The time point of administration of the second step radiolabeled ligand (radio- DOTA-biotin) significantly impacted the biodistribution of radioactivity in target tissues. Rapid clearance of the FP from the circulation rendered unnecessary the addition of a synthetic clearing agent in this model. These results support proceeding to anti-CD45 PRIT clinical trials for patients with both leukemia and lymphoma.
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Authors | Damian J Green, John M Pagel, Eneida R Nemecek, Yukang Lin, Aimee Kenoyer, Anastasia Pantelias, Donald K Hamlin, D Scott Wilbur, Darrell R Fisher, Joseph G Rajendran, Ajay K Gopal, Steven I Park, Oliver W Press |
Journal | Blood
(Blood)
Vol. 114
Issue 6
Pg. 1226-35
(Aug 06 2009)
ISSN: 1528-0020 [Electronic] United States |
PMID | 19515724
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- DOTA-biotin
- Organometallic Compounds
- Recombinant Fusion Proteins
- Biotin
- Streptavidin
- Leukocyte Common Antigens
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Topics |
- Animals
- Antibodies, Monoclonal
(pharmacology)
- Biotin
(analogs & derivatives, pharmacology)
- Drug Screening Assays, Antitumor
- Leukemia
(therapy)
- Leukocyte Common Antigens
(antagonists & inhibitors, immunology)
- Lymphoma
(therapy)
- Macaca fascicularis
- Mice
- Organometallic Compounds
(pharmacology)
- Radioimmunotherapy
(methods)
- Recombinant Fusion Proteins
(pharmacology)
- Streptavidin
(pharmacology)
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