Monitoring Glioma Growth and Tumor Necrosis with the U-SPECT-II/CT Scanner by Targeting Integrin αvβ3

The purpose of this study was to validate Tc-99m-3P-RGD(2) single-photon emission computed tomography/computed tomography (SPECT/CT) as an imaging tool to monitor alpha(v)beta(3) expression and tumor necrosis. The animal model was established by subcutaneous injection of 5 x 10(6) U87MG cells into the shoulder flank of each mouse. Imaging was performed using the U-SPECT-II/CT scanner (Milabs, Utrecht, the Netherlands). Tumor volumes were determined, and the tumor uptake of Tc-99m-3P-RGD(2) was calculated on the basis of SPECT/CT and compared to that from biodistribution. Immunohistochemistry was performed to determine CD31 and alpha(v)beta(3) expression levels. We found that the tumor detection limit was approximate to 0.5 mm(3) by Tc-99m-3P-RGD(2) SPECT/CT. The tumor uptake of Tc-99m-3P-RGD(2) from SPECT/CT was almost identical to that from biodistribution. The alpha(v)beta(3) was expressed mainly on blood vessels for the tumors of 0.2 to 0.5 cm(3). In larger tumors, tumor alpha(v)beta(3) expression increased due to more contribution from glioma cells. When tumors were > 0.5 cm(3), the %ID/cm(3) uptake of Tc-99m-3P-RGD(2) decreased because of necrosis. The overall relationship between the tumor size and % ID of Tc-99m-3P-RGD(2) was modeled as a quadratic polynomial fitting curve, with R-2 being >.95. Tc-99m-3P-RGD(2) SPECT/CT is excellent for monitoring alpha(v)beta(3) expression and tumor necrosis during tumor growth and may become a screening tool for patient selection before anti-alpha(v)beta(3) therapy.