TY - JOUR
T1 - Improved magnetic resonance molecular imaging of tumor angiogenesis by avidin-induced clearance of nonbound bimodal liposomes
AU - van Tilborg, Geralda A. F.
AU - Mulder, Willem J. M.
AU - van der Schaft, Daisy W. J.
AU - Reutelingsperger, Chris P. M.
AU - Griffioen, Arjan W.
AU - Strijkers, Gustav J.
AU - Nicolay, Klaas
PY - 2008
Y1 - 2008
N2 - Angiogenic, that is, newly formed, blood vessels play an important role in tumor growth and metastasis and are a potential target for tumor treatment. In previous studies, the alpha(v)beta(3) integrin, which is strongly expressed in angiogenic vessels, has been used as a target for Arg-Gly-Asp (RGD)-functionalized nanoparticulate contrast agents for magnetic resonance imaging-based visualization of angiogenesis. In the present study, the target-to-background ratio was increased by diminishing the nonspecific contrast enhancement originating from contrast material present in the blood pool. This was accomplished by the use of a so-called avidin chase, which allowed rapid clearance of non-bound paramagnetic RGD-biotin-liposomes from the blood circulation. C57BL/6 mice, bearing a B16F10 mouse melanoma, received RGD-functionalized or untargeted biotin-liposomes, which was followed by avidin infusion or no infusion. Precontrast, postcontrast, and postavidin T(1)-weighted magnetic resonance images were acquired at 6.3 T. Postcontrast images showed similar percentages of contrast-enhanced pixels in the tumors of mice that received RGD-biotin-liposomes and biotin-liposomes. Post avidin infusion this percentage rapidly decreased to precontrast levels for biotin-liposomes, whereas a significant amount of contrast-enhanced pixels remained present for RGD-biotin-liposomes. These results showed that besides target-associated contrast agent, the circulating contrast agent contributed significantly to the contrast enhancement as well. Ex vivo fluorescence microscopy confirmed association of the RGD-biotin-liposomes to tumor endothelial cells both with and without avidin infusion, whereas biotin-liposomes were predominantly found within the vessel lumen. The clearance methodology presented in this study successfully enhanced the specificity of molecular magnetic resonance imaging and opens exciting possibilities for studying detection limits and targeting kinetics of site-directed contrast agents in vivo
AB - Angiogenic, that is, newly formed, blood vessels play an important role in tumor growth and metastasis and are a potential target for tumor treatment. In previous studies, the alpha(v)beta(3) integrin, which is strongly expressed in angiogenic vessels, has been used as a target for Arg-Gly-Asp (RGD)-functionalized nanoparticulate contrast agents for magnetic resonance imaging-based visualization of angiogenesis. In the present study, the target-to-background ratio was increased by diminishing the nonspecific contrast enhancement originating from contrast material present in the blood pool. This was accomplished by the use of a so-called avidin chase, which allowed rapid clearance of non-bound paramagnetic RGD-biotin-liposomes from the blood circulation. C57BL/6 mice, bearing a B16F10 mouse melanoma, received RGD-functionalized or untargeted biotin-liposomes, which was followed by avidin infusion or no infusion. Precontrast, postcontrast, and postavidin T(1)-weighted magnetic resonance images were acquired at 6.3 T. Postcontrast images showed similar percentages of contrast-enhanced pixels in the tumors of mice that received RGD-biotin-liposomes and biotin-liposomes. Post avidin infusion this percentage rapidly decreased to precontrast levels for biotin-liposomes, whereas a significant amount of contrast-enhanced pixels remained present for RGD-biotin-liposomes. These results showed that besides target-associated contrast agent, the circulating contrast agent contributed significantly to the contrast enhancement as well. Ex vivo fluorescence microscopy confirmed association of the RGD-biotin-liposomes to tumor endothelial cells both with and without avidin infusion, whereas biotin-liposomes were predominantly found within the vessel lumen. The clearance methodology presented in this study successfully enhanced the specificity of molecular magnetic resonance imaging and opens exciting possibilities for studying detection limits and targeting kinetics of site-directed contrast agents in vivo
U2 - https://doi.org/10.1593/neo.08858
DO - https://doi.org/10.1593/neo.08858
M3 - Article
C2 - 19048124
SN - 1522-8002
VL - 10
SP - 1459
EP - 1469
JO - Neoplasia (New York, N.Y.)
JF - Neoplasia (New York, N.Y.)
IS - 12
ER -