RT Journal Article
SR Electronic
T1 Evaluation of 18F-clofarabine as a PET probe of deoxycytidine kinase in mouse and rat models of glioblastoma
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1612
OP 1612
VO 50
IS supplement 2
A1 C Wu
A1 P Chan
A1 W Chang
A1 H Wang
A1 R Liu
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/1612.abstract
AB 1612 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.