(99m)Tc-3P-RGD2 micro-single-photon emission computed tomography/computed tomography provides a rational basis for...

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.

(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.

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).

(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.