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  • Title: (99m)Tc-3P-RGD2 micro-single-photon emission computed tomography/computed tomography provides a rational basis for integrin αvβ3-targeted therapy.
    Author: Fu T, Qu W, Qiu F, Li Y, Shao G, Tian W, Hua Z, Zhang Y, Wang F.
    Journal: Cancer Biother Radiopharm; 2014 Nov; 29(9):351-8. PubMed ID: 25286251.
    Abstract:
    PURPOSE: This study was to demonstrate the utility of (99m)Tc-3P-RGD2 micro-single-photon emission computed tomography/computed tomography (SPECT/CT) for the integrin αvβ3 expression quantification in NCI-H446 and A549 lung cancer xenografts. MATERIALS AND METHODS: (99m)Tc-3P-RGD2 was prepared with high radiochemical purity (97%±2%) and showing high in vitro stability. The in vitro affinities of (99m)Tc-3P-RGD2 to NCI-H446 and A549 tumor cells were analyzed with γ-counter, while the in vivo uptakes in NCI-H446 and A549 xenografts were evaluated with micro-SPECT/CT. The region of interest was drawn over the tumor site and contralateral muscle on the SPECT/CT image, and the tumor to nontumor (T/NT) ratio was calculated to estimate αvβ3 expression and tumor uptake. The expressions of integrin αvβ3 in vitro and in vivo were analyzed using a flow cytometer and immunofluorescence. RESULTS: Micro-SPECT/CT demonstrated focal uptake in the tumors. T/NT ratio in NCI-H446 xenografts was significantly higher compared with the A549 tumor model, as 5.92±0.82 and 3.62±0.91, respectively, with p<0.05. In addition, integrin αvβ3 expression in NCI-H446 cells was significantly higher compared with the A549 cells, which was consistent with the imaging data. A linear relationship was observed between (99m)Tc-3P-RGD2 uptake and αvβ3 expression (R(2)=0.7667, p<0.001). CONCLUSION: (99m)Tc-3P-RGD2 SPECT/CT could be used to quantify integrin αvβ3 expression within tumors, providing a rational basis for integrin αvβ3-targeted cancer therapy.
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