PT  - JOURNAL ARTICLE
AU  - Moon, Byung Seok
AU  - Jang, Su Jin
AU  - Lee, Tae Sup
AU  - Lee, Byung Chul
AU  - Kang, Joo Hyun
AU  - Kim, Sang Eun
TI  - Synthesis and evaluation of fluorine-18 labeled ipomeanol as a CYP4B1 expression imaging probe
DP  - 2012 May 01
TA  - Journal of Nuclear Medicine
PG  - 1571--1571
VI  - 53
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/53/supplement_1/1571.short
4100  - http://jnm.snmjournals.org/content/53/supplement_1/1571.full
SO  - J Nucl Med2012 May 01; 53
AB  - 1571 Objectives 4-Ipomeanol (1-(3-furyl)-4-hydroxy-1-pentanone, 4-IPO) is naturally occurring pulmonary toxin. The major metabolic pathway of 4-IPO by cytochrome P450 enzymes involves furan ring opening leading to the formation of unsaturated α,β-aldehyde/ketone of dialdehyde reactive metabolite. Among of cytochrome P450 isozyme, CYP4B1, efficiently converts the prodrug, 4-IPO, to the alkylating metabolite which was highly reactive and binding covanently with tissues immediately at its site of formation. The present study is the development of F-18 labeled 4-IPO which has efficient targeting of CYP4B1 gene transfected cells. Methods The target compound, 5-fluoro-4-hydroxy-1-furan-3-yl-1-pentanone (F-4-IPO), was synthesized in twelve steps from 3-furaldehyde. [18F]F-4-IPO was synthesized from mesylate precursor through three-consecutive steps - displacement of [18F]fluoride, reduction and acidic-deprotection. C6-CYP4B1 cells were established using plasmid transfection. Evaluation of CYP4B1 expression level was confirmed by RT-PCR and MTT assay. Biodistribution study of [18F]F-4-IPO was investigated in normal rats. The cellular uptake of [18F]F-4-IPO and [3H]-4-IPO was performed in parental and CYP4B1-transfected cells and compared. Results The radiochemical yield of [18F]F-4-IPO was 20-35% with >95% of radiochemical purity. [18F]F-4-IPO showed over 96% stability until 120 min in human serum. Biodistribution of [18F]F-4-IPO in normal rats showed similar uptake patterns to [3H]-4-IPO. The cellular uptake ratios of [18F]F-4-IPO and [3H]-4-IPO in C6-CYP4B1 cells increased up to about 1.8 times at 30 min for [18F]F-4-IPO and 2.3 times at 360 min for [3H]-4-IPO higher than that of parental cells. Conclusions Our results show that [18F]F-4-IPO is an excellent analog of 4-IPO, and deserves further studies to evaluate its utility for PET imaging of CYP4B1 transfected cancer cells