Dual-modality optical and positron emission tomography imaging of vascular endothelial growth factor receptor on tumor vasculature using quantum dots.
OBJECTIVE
To date, the in vivo imaging of quantum dots (QDs) has been mostly qualitative or semiquantitative. The development of a dual-function positron emission tomography (PET)/near-infrared fluorescence (NIRF) probe might allow the accurate assessment of the tumor-targeting efficacy of QDs.


METHODS
An amine-functionalized QD was conjugated with VEGF protein and DOTA chelator for VEGFR-targeted PET/NIRF imaging after (64)Cu-labeling. The targeting efficacy of this dual functional probe was evaluated in vitro and in vivo through cell-binding assay, cell staining, in vivo optical/PET imaging, ex vivo optical/PET imaging, and histology.


RESULTS
The DOTA-QD-VEGF exhibited VEGFR-specific binding in both cell-binding assay and cell staining experiment. Both NIR fluorescence imaging and microPET showed VEGFR-specific delivery of conjugated DOTA-QD-VEGF nanoparticle and prominent reticuloendothelial system uptake. The U87MG tumor uptake of (64)Cu-labeled DOTA-QD was less than one percentage injected dose per gram (%ID/g), significantly lower than that of (64)Cu-labeled DOTA-QD-VEGF (1.52 +/- 0.6%ID/g, 2.81 +/- 0.3%ID/g, 3.84 +/- 0.4%ID/g, and 4.16 +/- 0.5%ID/g at 1, 4, 16, and 24 h post injection, respectively; n = 3). Good correlation was also observed between the results measured by ex vivo PET and NIRF organ imaging. Histologic examination revealed that DOTA-QD-VEGF primarily targets the tumor vasculature through a VEGF-VEGFR interaction.


CONCLUSIONS
We have successfully developed a QD-based nanoprobe for dual PET and NIRF imaging of tumor VEGFR expression. The success of this bifunctional imaging approach may render higher degree of accuracy for the quantitative targeted NIRF imaging in deep tissue.
Department of Radiology and Bio-X Program, School of Medicine, Stanford University, Stanford, CA 94305-5484, USA.
Kai
K
Chen
Zi-Bo
ZB
Li
Hui
H
Wang
Weibo
W
Cai
Xiaoyuan
X
Chen
D000588:Amines / Q000737:chemistry; D000818:Animals; D002614:Chelating Agents / Q000737:chemistry; D003301:Copper Radioisotopes / Q000737:chemistry; D005453:Fluorescence; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry; D005629:Frozen Sections; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D007259:Infrared Rays; D051379:Mice; D009369:Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging* / Q000473:pathology; D049268:Positron-Emission Tomography; D045663:Quantum Dots; D051381:Rats; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D013194:Staining and Labeling; D041622:Tomography, Optical; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000378:metabolism
D000588:Amines; D002614:Chelating Agents; D003301:Copper Radioisotopes; D005456:Fluorescent Dyes; D006573:Heterocyclic Compounds, 1-Ring; D042461:Vascular Endothelial Growth Factor A; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D040262:Receptors, Vascular Endothelial Growth Factor