Evaluation of 18F-clofarabine as a PET probe of deoxycytidine kinase in mouse and rat models of glioblastoma

Objectives Clofarabine, 2-chloro-9-(2-deoxy-2-fluoro-b-arabinofuranosyl)-adenine, a deoxycytidine kinase (dCK) inhibitor, is a next-generation tumor treatment drug. This study aimed to evaluate the fluorinated clofarabine (¹⁸F-clo) as a PET probe for assessing dCK activity of glioblastoma.

Methods Starting from benzoate-protected arabinose triflate, ¹⁸F-clofarabine was prepared in 3.5 h via a two-step synthesis with high radiochemical purity (≧98%) and acceptable radiochemical yield (10-15%, decay corrected). NOD-SCID mice were inoculated with glioblastoma (GBM) cells in the left thigh or in the brain. F344 rats were inoculated with GBM cells in the brain. The microPET imaging of ¹⁸F-clo was performed on day 12 after tumor inoculation.

Results GBM cells exhibited the moderate cell-to-medium (C/M) ratio (21.61) during 2 h incubation compared with other cells. MicroPET imaging showed different tumor contrasts depending on tumor-bearing sites and species. The tumor-to-muscle ratio was only 1.51 in tumor-bearing mice, but the radioactivity retained in the tumor in mouse brain was higher than normal brain to achieve 12.4 of tumor-to-brain ratio due to the low dCK activity in the brain. MicroPET did not detect the tumor growth in the brain of F344 rat.

Conclusions Fluorine-18 labeled clofarabine is successfully prepared via a two-step synthesis. ¹⁸F-clo is a promising PET probe for assessing dCK activity of glioblastoma in the mouse model, but not in rat model. ¹⁸F-clo seems not to be allowed to pass through blood-brain-barrier in F344 rat.