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

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Radermacher, Kim [UCL] Boutry, Sébastien Laurent, Sophie Vander Elst, Luce Mahieu, Isabelle Bouzin, Caroline [UCL] Magat, Julie [UCL] Grégoire, Vincent [UCL] Feron, Olivier [UCL] Jordan, Bénédicte [UCL] Gallez, Bernard [UCL]

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.

Document type Article de périodique (Journal article) – Article de recherche – Journal Article, Research Support, Non-U.S. Gov't
Access type Accès restreint
Publication date 2010
Language Anglais
Journal information "Contrast Media & Molecular Imaging" - Vol. 5, no. 5, p. 258-267 (2010)
Peer reviewed yes
Publisher JohnWiley & Sons Ltd. ((United Kingdom) Bognor Regis)
issn 1555-4309
e-issn 1555-4317
Publication status Publié
Affiliations UCL - SSS/LDRI - Louvain Drug Research Institute
UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique
UCL - SSS/IREC - Institut de recherche expérimentale et clinique
UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie
UCL - (SLuc) Service de radiothérapie oncologique
UCL - (SLuc) Service de médecine nucléaire
UCL - SSS/DDUV/GEHU - Génétique
MESH Subject X-Rays ; Phosphatidylserines - chemistry ; Oligopeptides - chemistry ; Neoplasms - pathology - radiotherapy ; Mice ; Magnetic Resonance Imaging ; Ferric Compounds - chemistry ; Electron Spin Resonance Spectroscopy ; Contrast Media - chemistry ; Cell Line, Tumor ; Cell Death - radiation effects ; Animals
Keywords MRI ; EPR ; Molecular imaging ; Cell death ; Ultrasmall iron oxide particles
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Bibliographic reference Radermacher, Kim ; Boutry, Sébastien ; Laurent, Sophie ; Vander Elst, Luce ; Mahieu, Isabelle ; et. al. Iron oxide particles covered with hexapeptides targeted at phosphatidylserine as MR biomarkers of tumor cell death. In: Contrast Media & Molecular Imaging, Vol. 5, no. 5, p. 258-267 (2010)
Permanent URL http://hdl.handle.net/2078.1/33505