68Ga-NODAGA-VEGF121 for in vivo imaging of VEGF receptor expression.

PURPOSE: Vascular endothelial growth factor (VEGF) is a crucial regulator of angiogenesis. In this study, we labeled VEGF121 with (68)Ga using a hydrophilic chelating agent, NODAGA and evaluated the resulting (68)Ga-NODAGA-VEGF121 for in vivo imaging of VEGF receptor (VEGFR) expression. METHODS: NODAGA-VEGF121 was prepared and its binding affinity for VEGFR2 was measured using (125)I-VEGF121. (68)Ga-NODAGA-VEGF121 was prepared by labeling NODAGA-VEGF121 with (68)GaCl3 followed by purification using a PD-10 column. Human aortic endothelial cell (HAEC) binding studies of (68)Ga-NODAGA-VEGF121 were performed at 37°C for 4 h. MicroPET imaging followed by biodistribution studies were performed in U87MG tumor-bearing mice injected with (68)Ga-NODAGA-VEGF121. Immunofluorescence staining of the tumor tissues was performed to verify VEGFR2 expression. RESULTS: Binding affinity of NODAGA-VEGF121 for VEGFR2 was found to be comparable to that of VEGF121. (68)Ga-NODAGA-VEGF121 was prepared in 47.8% yield with specific activity of 3.4 GBq/mg. (68)Ga-NODAGA-VEGF121 was avidly taken up by HAECs with a time-dependent increase from 9.88 %ID at 1 h to 20.86 %ID at 4h. MicroPET imaging of mice demonstrated high liver and spleen uptake with clear visualization of tumor at 1h after injection. ROI analysis of tumors revealed 2.53 ± 0.11 %ID/g at 4 h after injection. In the blocking study, tumor uptake was inhibited by 29% at 4 h. Subsequent biodistribution studies demonstrated tumor uptake of 2.38 ± 0.15 %ID/g. Immunofluorescence staining of the tumor tissues displayed high level of VEGFR2 expression. CONCLUSIONS: These results demonstrate that (68)Ga-NODAGA-VEGF121 led to VEGFR-specific distribution in U87MG tumor-bearing mice. This study also suggests that altered physicochemical properties of VEGF121 after radiolabeling may affect biodistribution of the radiolabeled VEGF121.