Herceptin Research Today is a free monthly online journal that collates and summarizes the latest research about Herceptin, including details on side-effects, breast cancer, treatment, therapy.

PAMAM dendrimer-based contrast agents for MR imaging of Her-2/neu receptors by a three-step pretargeting approach.

Zhu W, Okollie B, Bhujwalla ZM, Artemov D

JHU ICMIC Program, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

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.

Published 3 April 2008 in Magn Reson Med, 59(4): 679-85.
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