Document Detail


The ratio of maximum percent tumour accumulations of the pretargeting agent and the radiolabelled effector is independent of tumour size.
MedLine Citation:
PMID:  19811906     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Our previous studies have indicated that the optimal dosage ratio of pretargeting antibody to effector is proportional to their maximum percent tumour accumulations (MPTAs). This study quantitatively describes how both MPTAs and their ratio change with tumour size, to simplify pretargeting optimisation when tumour size varies. The CC49 antibody dosages below saturation of the tumour antigen level were first examined for the LS174T tumour mouse model. Then the MPTAs of the antibody in mice bearing tumours of different sizes were determined, always at antibody dosages below antigen saturation. Historical data from this laboratory were used to collect the MPTAs of the (99m)Tc-cMORF effector for different tumour sizes, always at effector dosages below that required to saturate the MORF in tumour. The MPTAs versus tumour sizes for both the antibody and the effector were fitted non-linearly. The best fit of the antibody MPTA (Y(antibody)) with tumour size (x) in grams was Y(antibody)=19.00 x(-0.65) while that for the effector was Y(effector)=4.51x(-0.66). Thus, even though the MPTAs of both vary with tumour size, the ratio (Y(antibody)/Y(effector)) is a constant at 4.21. In conclusion, the MPTA ratio of the antibody to the effector was found to be constant with tumour size, an observation that will simplify pretargeting optimisation because remeasurement of the optimum dosage ratio for different tumour sizes can be avoided. Theoretical considerations also suggest that this relationship may be universal for alternative antibody/effector pairs and for different target models, but this must be experimentally confirmed.
Authors:
Guozheng Liu; Shuping Dou; Minmin Liang; Xiangji Chen; Mary Rusckowski; Donald J Hnatowich
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-10-05
Journal Detail:
Title:  European journal of cancer (Oxford, England : 1990)     Volume:  45     ISSN:  1879-0852     ISO Abbreviation:  Eur. J. Cancer     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-09     Completed Date:  2010-01-27     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  9005373     Medline TA:  Eur J Cancer     Country:  England    
Other Details:
Languages:  eng     Pagination:  3098-103     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Neoplasm / metabolism*
Antineoplastic Agents / pharmacokinetics
Colonic Neoplasms / metabolism*,  pathology
Disease Models, Animal
Dose-Response Relationship, Immunologic
Indium Radioisotopes / pharmacokinetics
Male
Mice
Mice, Nude
Morpholines / pharmacokinetics*
Morpholinos
Neoplasm Transplantation
Radiopharmaceuticals / pharmacokinetics
Technetium Compounds / pharmacokinetics
Tissue Distribution
Grant Support
ID/Acronym/Agency:
CA107360/CA/NCI NIH HHS; CA94994/CA/NCI NIH HHS; R01 CA094994/CA/NCI NIH HHS; R01 CA094994-07/CA/NCI NIH HHS; R21 CA107360-02/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Neoplasm; 0/Antineoplastic Agents; 0/B72.3 antibody; 0/Indium Radioisotopes; 0/Morpholines; 0/Morpholinos; 0/Radiopharmaceuticals; 0/Technetium Compounds
Comments/Corrections

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