TY - JOUR
T1 - Molecular imaging of tumor angiogenesis using αvβ3-integrin targeted multimodal quantum dots
AU - Mulder, Willem J.M.
AU - Castermans, Karolien
AU - Van Beijnum, Judy R.
AU - Oude Egbrink, Mirjam G.A.
AU - Chin, Patrick T.K.
AU - Fayad, Zahi A.
AU - Löwik, Clemens W.G.M.
AU - Kaijzel, Eric L.
AU - Que, Ivo
AU - Storm, Gert
AU - Strijkers, Gustav J.
AU - Griffioen, Arjan W.
AU - Nicolay, Klaas
PY - 2009/3
Y1 - 2009/3
N2 - Molecular imaging of angiogenesis is urgently needed for diagnostic purposes such as early detection, monitoring of (angiostatic) therapy and individualized therapy. Multimodality molecular imaging is a promising and refined technique to study tumor angiogenesis, which has so far been largely unexplored due to the lack of suitable multimodal contrast agents. Here, we report on the application of a novel αvβ3-specific quantum dot-based nanoparticle, which has been optimized for both optical and magnetic resonance detection of tumor angiogenesis. Upon intravenous injection of RGD-pQDs in tumor-bearing mice, intravital microscopy allowed the detection of angiogenically activated endothelium at cellular resolution with a small scanning window and limited penetration depth, while magnetic resonance imaging was used to visualize angiogenesis at anatomical resolution throughout the entire tumor. Fluorescence imaging allowed whole-body investigation of angiogenic activity. Using these quantum dots and the aforementioned imaging modalities, the angiogenic tumor vasculature was readily detected with the highest angiogenic activity occurring in the periphery of the tumor. This nanoparticle may be employed for multimodality imaging of a variety of diseases that are accompanied by activation of endothelial cells. Furthermore, the current technology might be developed for molecular imaging of other pathophysiological processes.
AB - Molecular imaging of angiogenesis is urgently needed for diagnostic purposes such as early detection, monitoring of (angiostatic) therapy and individualized therapy. Multimodality molecular imaging is a promising and refined technique to study tumor angiogenesis, which has so far been largely unexplored due to the lack of suitable multimodal contrast agents. Here, we report on the application of a novel αvβ3-specific quantum dot-based nanoparticle, which has been optimized for both optical and magnetic resonance detection of tumor angiogenesis. Upon intravenous injection of RGD-pQDs in tumor-bearing mice, intravital microscopy allowed the detection of angiogenically activated endothelium at cellular resolution with a small scanning window and limited penetration depth, while magnetic resonance imaging was used to visualize angiogenesis at anatomical resolution throughout the entire tumor. Fluorescence imaging allowed whole-body investigation of angiogenic activity. Using these quantum dots and the aforementioned imaging modalities, the angiogenic tumor vasculature was readily detected with the highest angiogenic activity occurring in the periphery of the tumor. This nanoparticle may be employed for multimodality imaging of a variety of diseases that are accompanied by activation of endothelial cells. Furthermore, the current technology might be developed for molecular imaging of other pathophysiological processes.
KW - Angiogenesis
KW - Fluorescence imaging
KW - Intravital microscopy
KW - Magnetic resonance imaging
KW - Multimodality imaging
KW - Quantum dots
UR - http://www.scopus.com/inward/record.url?scp=61449222764&partnerID=8YFLogxK
U2 - 10.1007/s10456-008-9124-2
DO - 10.1007/s10456-008-9124-2
M3 - Article
C2 - 19067197
AN - SCOPUS:61449222764
SN - 0969-6970
VL - 12
SP - 17
EP - 24
JO - Angiogenesis
JF - Angiogenesis
IS - 1
ER -