[18F]Fluorinated estradiol derivatives for oestrogen receptor imaging: impact of substituents, formulation and specific activity on the biodistribution in breast tumour-bearing mice.

Abstract

The biodistribution and tumour uptake of a series of 16alpha-[(18)F]fluoroestradiol ([18F]FES) derivatives was determined in oestrogen receptors-positive (ER+) tumour-bearing mice to assess the impact of substituents, formulation and specific activity on target tissue uptake. MC4-L2 and MC7-L1 murine ER+ cells were inoculated in Balb/c mice. The animals were injected with various [(18)F]FES derivatives substituted with 2- or 4-fluorine and/or an 11beta-methoxy group. The radiopharmaceuticals were formulated in 10% ethanol/saline or 10% ethanol/lipid emulsion. The organs were counted, and radioactivity concentrations were expressed as the percentage of the injected dose per gram tissue (%ID/g). To estimate the effect of specific activity on tumour uptake, the 4-fluoro-11beta-methoxy-16alpha-[(18)F]-fluoroestradiol (4F-M[(18)F]FES) was co-injected with different concentrations of non-radioactive estradiol to give an in vivo competitive inhibition curve. 4F-M[(18)F]FES exhibited the highest average uterine uptake (%ID/g = 15.7 +/- 2.1). The highest uptake by the two mammary tumours was observed with [(18)F]FES (%ID/g = 3.1 and 3.4 +/- 0.3) and 11beta-methoxy-16alpha[(18)F]-fluoroestradiol (M-[(18)F]FES) (%ID/g = 3.2 and 3.3 +/- 0.6), followed by 4F-M[(18)F]FES (%ID/g = 2.5 and 2.3 +/- 0.3). The formulation had little influence on the biodistribution pattern. Co-injection with a total mass of estradiol >10(-10) mol blocked 4F-M[(18)F]FES tumour uptake. All of the radiolabelled estradiol derivatives achieved significant target tissue uptake in vivo, both in ER+ tumours and the uterus. The formulation had little impact on the biodistribution of these compounds but some compounds (4F-M[(18)F]FES, M-[(18)F]FES and [(18)F]FES) had more favourable target tissue uptake and target-to-background ratios.