Abstract
1699
Objectives [18F]galacto-RGD ([18F]gRGD) is a PET-tracer for αvβ3-integrin imaging which might serve as potential surrogate parameter of angiogenic activity. However, little is yet known about the correlation of the PET signal of [18F]gRGD with other key players of the angiogenic cascade. Thus, we evaluated the tracer uptake of [18F]gRGD in melanoma xenografts with altered levels of αvβ3 expression and correlated the uptake with the corresponding gene expression profile. We also compared these results with the uptake of [18F]FDG as an unspecific tracer for imaging tumor metabolism.
Methods We performed microPET/CT (Siemens) scans 75 min p.i. of [18F]gRGD and 45 min p.i. of [18F]FDG, respectively of nine BALB/c nude mice with two tumor xenografts with either high (M21) or low αvβ3 expression on tumor cells (M21-L). Total tumor RNA of 14 different tumor samples was used for gene expression profiling using human gene arrays (Affymetrix).
Results MicroPET scans of M21 melanoma showed significantly higher [18F]gRGD tracer uptake (x±SDM21=1.10±0.17%ID/g) compared to the M21-L population (x±SDM21-L=0.63±0.24%ID/g; p=0.0004). However, no differences in the glucose metabolism, addressed by [18F]FDG, was detected for M21 (x±SDM21=9.57±4.17%ID/g) compared to M21-L tumors (x±SDM21-L=7.81±2.87%ID/g; p=0.301). We also observed a separation in the gene expression profile of melanoma corresponding with high and low [18F]gRGD uptake. We found 199 probe sets with significant (FDR<5%) differential expression higher than 2fold between both groups. Besides αvβ3, we identified other factors like CEACAM1 which point to functional differences in cell-cell adhesion.
Conclusions These results suggest that imaging of αvβ3 expression by [18F]gRGD PET might be able to identify different tumor genotypes correlated with cell-cell interactions. Moreover, this tracer seems to be better suited than [18F]FDG to differentiate these tumor genotypes