1. Contrast Media Mol Imaging. 2010 Sep-Oct;5(5):258-67.

Iron oxide particles covered with hexapeptides targeted at phosphatidylserine as 
MR biomarkers of tumor cell death.

Radermacher KA, Boutry S, Laurent S, Elst LV, Mahieu I, Bouzin C, Magat J,
Gregoire V, Feron O, Muller RN, Jordan BF, Gallez B.

Biomedical Magnetic Resonance Unit, Louvain Drug Research Institute, Université
Catholique de Louvain, Brussels, Belgium.

The aim of the study was to evaluate the ability of a new MR contrast agent to
detect cell death as a biomarker of the efficacy of anti-cancer treatment. The
phosphatidylserine-targeted hexapeptide (E3) was coupled to pegylated ultrasmall 
iron oxide nanoparticles (USPIO) that can be detected by magnetic resonance
imaging (MRI) and by electron paramagnetic resonance (EPR). USPIO binding to
staurosporine-treated TLT (transplantable liver tumor) cells, evaluated by X-Band
EPR, indicated twice as much binding of USPIO grafted with the E3 peptide,
compared with USPIO grafted with a scrambled peptide or ungrafted USPIO. In vivo 
experiments were carried out using TLT cells implanted intramuscularly into NMRI 
mice, and tumor cell death was induced by irradiation. After intravenous
injection of the different types of USPIO, the accumulation of contrast agent was
evaluated ex vivo by X-band EPR, in vivo by L-band EPR and by T(2)-weighted MRI. 
In irradiated tumors there was greater accumulation of the targeted USPIO
particles compared with control particles or compared with the targeted particles
in untreated tissues. In conclusion, phosphatidylserine-targeting of USPIO
particles can detect dying tissues. This molecular targeted system should be
evaluated further as a potential biomarker of tumor response to treatment.


PMID: 20973111 [PubMed - in process]