Predicting the biodistribution of radiolabeled cMORF effector in MORF-pretargeted mice
Document Type
Journal ArticlePublication Date
2006-10-06Keywords
*AlgorithmsAnimals
Cell Line, Tumor
Colonic Neoplasms
Computer Simulation
Drug Delivery Systems
Metabolic Clearance Rate
Mice
Mice, Nude
*Models, Biological
Morpholines
Organ Specificity
Radiopharmaceuticals
Technetium
Tissue Distribution
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
PURPOSE: Pretargeting with phosphorodiamidate morpholino oligomers (MORFs) involves administration of a MORF-conjugated anti-tumor antibody such as MN14 as a pretargeting agent before that of the radiolabeled complementary MORF (cMORF) as the effector. The dosages of the pretargeting agent and effector, the pretargeting interval, and the detection time are the four pretargeting variables. The goal of this study was to develop a semiempirical description capable of predicting the biodistribution of the radiolabeled effector in pretargeted mice and then to compare predictions with experimental results from pretargeting studies in tumored animals in which the pretargeting interval and the detection time were both fixed but the dosages of both the effector and the pretargeting agent were separately varied. METHODS: Pretargeting studies in LS174T tumored mice were performed using the anti-CEA antibody MN14 conjugated with MORF and the cMORF radiolabeled with (99m)Tc. A description was developed based on our previous observations in the same mouse model of the blood and tumor levels of MORF-MN14, accessibility of MORF-MN14 to labeled cMORF, the tumor accumulation of labeled cMORF relative to MORF-MN14 levels therein, and the kidney accumulation of labeled cMORF. The predicted values were then compared with the experimental values. RESULTS: The predicted biodistribution of the radiolabeled effector and the experimental data were in gratifying agreement in normal organs, suggesting that the description of the pretargeting process was reliable. The tumor accumulations occasionally fell outside two standard deviations of that predicted, but after tumor size correction, good agreement between predicted and experimental values was observed here as well. CONCLUSION: A semiempirical description of the biodistribution of labeled cMORF was capable of predicting the biodistribution of the radiolabeled effector in the pretargeted tumored mouse model, demonstrating that the underlying pretargeting concepts are correct. We believe that the approach described herein may be applied to any of the alternative pretargeting approaches and animal tumor models currently under investigation. Furthermore, appreciation of the concepts may provide a rationale for selecting dosages and timings in human pretargeting studies as an alternative to pure empirical means.Source
Eur J Nucl Med Mol Imaging. 2007 Feb;34(2):237-46. Link to article on publisher's site
DOI
10.1007/s00259-006-0222-3Permanent Link to this Item
http://hdl.handle.net/20.500.14038/42186PubMed ID
17021815Related Resources
ae974a485f413a2113503eed53cd6c53
10.1007/s00259-006-0222-3