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 T1 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.
Original language | English (US) |
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Pages (from-to) | 679-685 |
Number of pages | 7 |
Journal | Magnetic resonance in medicine |
Volume | 59 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2008 |
Keywords
- Her-2/neu receptors
- MRI
- PAMAM dendrimer
- Pretargeting
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging