| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Novel Approaches to Molecular ImagingOncology |
1 Pharmacology, University of California Los Angeles, Los Angeles, California; 2 Chemistry, UC Davis, Davis, California
|
|
102
Objectives: To develop an engineered antibody fragment as a new reporter gene for in vivo PET imaging.
Methods: The reporter gene, designated DAbR1, consists of the scFv fragment of the anti-DOTA antibody 2D12.5 fused to the CD4 transmembrane domain. The corresponding reporter probe is Y*-AABD, a DOTA complex that irreversibly binds to a cysteine residue in the 2D12.5 antibody. U-87 glioma cells were stable transfected with DAbR1 expression plasmid.
Results: Flow cytometry revealed high-level expression of the DAbR1 protein on the cell surface. In xenografts models, the tumor uptake in DAbR1 tumors was 8.4 ± 0.13 % at 1 h and 5.6 ± 0.62 % ID/g at 24 h after injection with AABD-90Y. Uptake by U87 wild type tumors was 0.33 ± 0.02 % at 1 h and 0.23 ± 0.017 % ID/g at 24 h. PET images with Y86-DAbR1 demonstrated intense tumor uptake and low background activity at 24 h.
Conclusions: These findings together with the predicted low immunogenicity of the humanized version of the 2D12.5 antibody indicate that DAbR1/Y*-AABD is a promising reporter gene/reporter probe combination for PET imaging.
Research Support: UCLA ICMIC Grants
| ||||||||||||||||||||||||||||||||||||||
