Adding a clearing agent to pretargeting does not lower the tumor accumulation of the effector as predicted
Authors
Liu, GuozhengDou, Shuping
Chen, Xiangji
Chen, Ling
Liu, Xinrong
Rusckowski, Mary
Hnatowich, Donald J.
UMass Chan Affiliations
Department of Radiology, Division of Nuclear MedicineDocument Type
Journal ArticlePublication Date
2010-12-01Keywords
Animal StructuresAnimals
Antibodies, Neoplasm
Antigen-Antibody Reactions
Antigens, Neoplasm
Antineoplastic Agents
Avidin
Biotin
Cell Line, Tumor
Glycoproteins
Humans
Immunoconjugates
Mice
Mice, Inbred Strains
Mice, Nude
Morpholines
Morpholinos
Neoplasms
Technetium
Tissue Distribution
clearing agent
prediction model
pretargeting
tumor accumulation
Medicinal and Pharmaceutical Chemistry
Neoplasms
Radiology
Therapeutics
Metadata
Show full item recordAbstract
Clearing agents are often used in pretargeting despite the potential for decreased tumor accumulation of the effector. However, according to the authors' semiempirical model, a clearing agent should not necessarily decrease tumor accumulation. In this study, the authors have added a clearing step to their model-morpholino phosphorodiamidate oligomer (MORF)/complement MORF (cMORF) pretargeting system-to confirm this prediction. The CC49 antibody was conjugated with both biotin and an 18 mer MORF. The influence of avidin on antibody clearance was first evaluated in normal mice in which each animal received 30 mug of MORF-CC49-biotin, 0-70 mug of avidin 1 day later, and 1.2 mug of (9)(9)(m)Tc-cMORF 3 hours later, with sacrifice at 3 hours. Thereafter, a pretargeting study in mice bearing an LS174T tumor was performed at a 34 mug avidin dosage. In normal mice, the blood level of (9)(9)(m)Tc-cMORF fell by 60% at an avidin dosage of 10 mug or higher. In tumored mice, avidin produced a similar reduction in blood but had no influence on tumor level, which remained at 6.30% ID/g as predicted. In conclusion, in addition to the expected reduced effector levels in blood and normal tissues, a reduction in tumor accumulation was avoided when adding a clearing agent as predicted.Source
Cancer Biother Radiopharm. 2010 Dec;25(6):757-62. doi: 10.1089/cbr.2010.0800. Link to article on publisher's siteDOI
10.1089/cbr.2010.0800Permanent Link to this Item
http://hdl.handle.net/20.500.14038/48400PubMed ID
21204772Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1089/cbr.2010.0800