Radiosynthesis and Preliminary Biological Evaluation of F-Fluoropropionyl-Chlorotoxin as a Potential PET Tracer for Glioma Imaging.

PURPOSES

Chlorotoxin can specifically bind to matrix metalloproteinase 2 (MMP-2), which are overexpressed in the glioma. In this work, radiosynthesis of [F]-fluoropropionyl-chlorotoxin ([F]-FP-chlorotoxin) as a novel PET tracer was investigated, and biodistribution in vivo and PET imaging were performed in the C6 glioma model.

PROCEDURES

[F]-FP-chlorotoxin was prepared from the reaction of chlorotoxin with [F]-NFB (4-nitrophenyl 2-[F]-fluoropropionate), which was synthesized from multistep reactions. Biodistribution was determined in 20 normal Kunming mice. Small-animal PET imaging with [F]-FP-chlorotoxin was performed on the same rats bearing orthotopic C6 glioma at different time points (60 min, 90 min, and 120 min) after injection and compared with 2-deoxy-2-[F] fluoro-D-glucose ([F]-FDG).

RESULTS

[F]-FP-Chlorotoxin was successfully synthesized in the radiochemical yield of 41% and the radiochemical purity of more than 98%. Among all the organs, the brain had the lowest and stable uptake of [F]-FP-chlorotoxin, while the kidney showed the highest uptake. Compared with [F]-FDG, a low uptake of [F]-FP-chlorotoxin was detected in normal brain parenchyma and a high accumulation of [F]-FP-chlorotoxin was found in the gliomas tissue. The glioma to normal brain uptake ratio of [F]-FP-chlorotoxin was higher than that of [F]-FDG. Furthermore, the uptake of [F]-FP-chlorotoxin at 90 min after injection was better than that at 60 min after injection.

CONCLUSIONS

Compared with [F]-FDG, [F]-FP-chlorotoxin has a low and stable uptake in normal brain parenchyma. [F]-FP-Chlorotoxin seems to be a potential PET tracer with a good performance in diagnosis of the glioma.