Radiosynthesis and Preliminary Biological Evaluation of ¹⁸F-Fluoropropionyl-Chlorotoxin as a Potential PET Tracer for Glioma Imaging.

ABSTRACT:

Purposes

Chlorotoxin can specifically bind to matrix metalloproteinase 2 (MMP-2), which are overexpressed in the glioma. In this work, radiosynthesis of [¹⁸F]-fluoropropionyl-chlorotoxin ([¹⁸F]-FP-chlorotoxin) as a novel PET tracer was investigated, and biodistribution in vivo and PET imaging were performed in the C6 glioma model.

Procedures

[¹⁸F]-FP-chlorotoxin was prepared from the reaction of chlorotoxin with [¹⁸F]-NFB (4-nitrophenyl 2-[¹⁸F]-fluoropropionate), which was synthesized from multistep reactions. Biodistribution was determined in 20 normal Kunming mice. Small-animal PET imaging with [¹⁸F]-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-[¹⁸F] fluoro-D-glucose ([¹⁸F]-FDG).

Results

[¹⁸F]-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 [¹⁸F]-FP-chlorotoxin, while the kidney showed the highest uptake. Compared with [¹⁸F]-FDG, a low uptake of [¹⁸F]-FP-chlorotoxin was detected in normal brain parenchyma and a high accumulation of [¹⁸F]-FP-chlorotoxin was found in the gliomas tissue. The glioma to normal brain uptake ratio of [¹⁸F]-FP-chlorotoxin was higher than that of [¹⁸F]-FDG. Furthermore, the uptake of [¹⁸F]-FP-chlorotoxin at 90 min after injection was better than that at 60 min after injection.

Conclusions

Compared with [¹⁸F]-FDG, [¹⁸F]-FP-chlorotoxin has a low and stable uptake in normal brain parenchyma. [¹⁸F]-FP-Chlorotoxin seems to be a potential PET tracer with a good performance in diagnosis of the glioma.

SUBMITTER: Zhao J 

PROVIDER: S-EPMC6317094 | biostudies-literature |

REPOSITORIES: biostudies-literature