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MR molecular imaging and fluorescence microscopy for identification of activated tumor endothelium using a bimodal lipidic nanoparticle
Author(s) -
Mulder Willem J. M.,
Strijkers Gustav J.,
Habets Jo W.,
Bleeker Egbert J. W.,
Schaft Daisy W. J.,
Storm Gert,
Koning Gerben A.,
Griffioen Arjan W.,
Nicolay Klaas
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4145fje
Subject(s) - liposome , fluorescence microscope , angiogenesis , ex vivo , fluorescence lifetime imaging microscopy , in vivo , integrin , chemistry , endothelium , biophysics , molecular imaging , confocal microscopy , pathology , microbiology and biotechnology , fluorescence , cancer research , cell , biology , in vitro , medicine , biochemistry , physics , quantum mechanics , endocrinology
In oncological research, there is a great need for imaging techniques that specifically identify angiogenic blood vessels in tumors on the basis of differences in the expression level of biomolecular markers. In the angiogenic cascade, different cell surface receptors, including the αvβ3‐integrin, are strongly expressed on activated endothelial cells. In the present study, we aimed to image angiogenesis by detecting the expression of αvβ3 in tumor bearing mice with a combination of magnetic resonance imaging (MRI) and fluorescence microscopy. To that end, we prepared MR‐detectable and fluorescent liposomes, which carry ∼700 αvβ3‐specific RGD peptides per liposome. RGD competition experiments and RAD‐conjugated liposomes were used as controls for specificity. In vivo, both RAD liposomes and RGD liposomes gave rise to signal increase on T 1 ‐weighted MR images. It was established by the use of ex vivo fluorescence microscopy that RGD liposomes and RAD liposomes accumulated in the tumor by different mechanisms. RGD liposomes were specifically associated with activated tumor endothelium, while RAD liposomes were located in the extravascular compartment. This study demonstrates that MR molecular imaging of angiogenesis is feasible by using a targeted contrast agent specific for the αvβ3‐integrin, and that the multimodality imaging approach gave insight into the exact mechanism of accumulation in the tumor.