Synthesis of 11C-Radiolabeled Eribulin as a Companion Diagnostics PET Tracer for Brain Glioblastoma

The successful 11C-radiolabeling of eribulin, an analog of the marine natural product halichondrin B, and an approved anticancer drug for the treatment of breast cancer and lipo-sarcoma, is reported. A rapid sequence involving a nitroaldol reaction with [11C]nitromethane and subsequent reduction of the nitro group enabled the introduction of a carbon-11 atom at the C35-position of eribulin. Optimization of the reaction and purification conditions led to a reproducible synthetic method for [35-11C]eribulin with 248 << 104 MBq of radioactivity, 88.2 +/- 5.8% radiochemical purity, and 132 +/- 32 MBq/nmol molar activity. The total synthetic time was 38.0 +/- 1.3 min (n = 12). PET imaging using mice bearing brain tumors revealed a specific accumulation of [35-11C]eribulin in tumors without any significant metabolic changes. These results indi-cate the applicability of [35-11C]eribulin for the quantitative measurement of eribulin migration into tumor tissue, which would be beneficial for exploring the application of eribulin for glioblastoma treatment and estimating the appropriate dosage for each patient.

Automated summary

This study reports the successful 11C-radiolabeling of eribulin, an approved anticancer drug, which enables the quantitative measurement of eribulin migration into tumor tissue. The optimized synthetic method provides a reproducible way to produce [35-11C]eribulin with high radiochemical purity and molar activity. PET imaging using mice shows specific accumulation of [35-11C]eribulin in tumors without significant metabolic changes.