CONTEXT: Dr. Francis Blankenberg and colleagues at Stanford University's nuclear medicine department have developed a nondestructive way, based on two fragments of human RNAse I, to radiolabel the tumor angiogenesis marker VEGF (vascular endothelial growth factor). The larger and sturdier standardized fragment, the "adapter protein," is radiolabeled with technetium-99m. It is then simply mixed with a fusion protein consisting of the smaller complementary fragment, the "docking tag," and targeting protein VEGF. The two proteins self-assemble into a Tc-99m-VEGF targeting complex for radionuclide imaging.
RESULTS: Using bioluminescent imaging (BLI) and radionuclide imaging, the researchers tracked the growth of subcutaneous and lung tumors in mice implanted or injected with luciferase-expressing murine mammary adenocarcinoma cells. One hour after injecting the tracer, planar images were acquired that showed significantly increased uptake of VEGF compared with the single-chain Hu-P4G7 anti-VEGF-R2 antibody radiolabeled complexes. Both tracers bound to the VEGF-R2 receptor, but only VEGF was internalized into tumor endothelial cells.
IMAGE: A: Planar whole-body BLI of mouse with right shoulder tumor. B: Radionuclide image of same mouse after injection of Tc-99m-HuS/Hu-VEGF. C: Radionuclide image of mouse with left shoulder tumor after injection of Tc-99m-HuS/Hu-P4G7. D: BLI of same mouse.
IMPLICATIONS: The VEGF imaging complex is stable and capable of routinely targeting lesions of about 1 mm in diameter in vivo. The Stanford team expects to develop a similar approach for delivery of other targeting proteins, according to Blankenberg.
"It is anticipated that this technique could be used to create a library of fusion proteins, all of which could be rapidly and nondestructively labeled using the identical radiochemistry," he said.