99m Tc-3P-RGD 2 Micro-Single-Photon Emission Computed Tomography/Computed Tomography Provides a Rational Basis for Integrin α v β 3 -Targeted Therapy

Abstract

Purpose:

This study was to demonstrate the utility of ^99mTc-3P-RGD₂ micro-single-photon emission computed tomography/computed tomography (SPECT/CT) for the integrin α_vβ₃ expression quantification in NCI-H446 and A549 lung cancer xenografts.

Materials and Methods:

^99mTc-3P-RGD₂ was prepared with high radiochemical purity (97%±2%) and showing high in vitro stability. The in vitro affinities of ^99mTc-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 α_vβ₃ expression and tumor uptake. The expressions of integrin α_vβ₃ 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 α_vβ₃ 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 ^99mTc-3P-RGD₂ uptake and α_vβ₃ expression (R² =0.7667, p<0.001).

Conclusion:

^99mTc-3P-RGD₂ SPECT/CT could be used to quantify integrin α_vβ₃ expression within tumors, providing a rational basis for integrin α_vβ₃-targeted cancer therapy.