Abstract
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Objectives It would be important to increase the diagnostic specificity and sensitivity of hepatoma carcinoma cells (HCC) due to its high occurring and fatality rate. Combining two or even more modalities together will be beneficial to achieve higher performance on HCC imaging. We aimed to develop a hybrid MRI/SPECT probe based on VEGF antagonist bevacizumab for HCC localization, staging and therapy monitoring.
Methods Firstly, bevacizumab was labeled with 125I and injected to HepG2 tumored mice for microSPECT/CT imaging to test its specificity and targeting. Then, a DTPA and PEG modified ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles with the average diameters of <20 nm were conjugated with bevacizumab. The nanoparticles were labeled with 99mTc and injected into HepG2 tumored mice, microSPCET/CT scannings were performed again to evaluate the tumor targeting and pharmacokinetic. After imaging, the mice were sacrificed, and the tumors were removed for CD34, VEGF and Prussian blue staining.
Results 125I labeled bevacizumab could be targeted to HepG2 tumor, but shows slow pharmacokinetics in vivo. From 2 h to 24 h, tumor uptake slightly changed from 2.3% to 2.5% (ID%/g). However, 99mTc labeled bevacizumab nanoparticle shows faster blood clearance and increased tumor uptake with 3.88% of ID%/g at 24 h p.i.. CD34 and VEGF staining verified HepG2 tumor is hypervascular and VEGF positive. Prussian blue staining shows the bevacizumab nanaoparticle can be targeted to HepG2 tumor cells.
Conclusions This preliminary data shows 99mTc-USPIO-Bevacizumab is a promising hybrid SPECT/MRI imaging agent, which could be used for HepG2 carcinomas diagnosis and therapy monitoring.