PAMAM dendrimer-based contrast agents for MR imaging of Her-2/neu receptors by a three-step pretargeting approach
✍ Scribed by Wenlian Zhu; Baasil Okollie; Zaver M. Bhujwalla; Dmitri Artemov
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 679 KB
- Volume
- 59
- Category
- Article
- ISSN
- 0740-3194
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✦ Synopsis
Abstract
Pretargeting of receptors is a useful approach in molecular imaging and therapy to reduce background noise or toxicity and enhance selectivity. In this study a three‐step pretargeting approach that includes a biotinylated antibody, avidin/streptavidin, and a biotinylated imaging agent is described. A PAMAM dendrimer generation 4 (G4D)‐based MRI T~1~ agent biotin‐G4D‐DTPA‐Gd (bG4D‐Gd) and its sister compound with remaining free surface amine groups blocked by succinic anhydride to reduce positive charges (bG4D‐Gd‐SA) were synthesized. Limited selective enhancement in MRI was observed in a Her‐2/neu mouse tumor xenograft by this three‐step pretargeting approach that includes biotinylated trastuzumab, avidin and bG4D‐Gd, or bG4D‐Gd‐SA. However, these dendrimer‐based MRI agents with molecular weight around 29 kD reached and remained in the tumor through the enhanced permeability and retention effect. Prolonged and extensive accumulation of both bG4D‐Gd and b‐G4‐Gd‐SA in the kidneys was also observed. Magn Reson Med, 2008. © 2008 Wiley‐Liss, Inc.