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

The biodistribution and tumour uptake of a series of 16α-[¹⁸F]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 [¹⁸F]FES derivatives substituted with 2- or 4-fluorine and/or an 11β-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-11β-methoxy-16α-[¹⁸F]-fluoroestradiol (4F-M[¹⁸F]FES) was co-injected with different concentrations of non-radioactive estradiol to give an in vivo competitive inhibition curve. 4F-M[¹⁸F]FES exhibited the highest average uterine uptake (%ID/g = 15.7 ± 2.1). The highest uptake by the two mammary tumours was observed with [¹⁸F]FES (%ID/g = 3.1 and 3.4 ± 0.3) and 11β-methoxy-16α[¹⁸F]-fluoroestradiol (M-[¹⁸F]FES) (%ID/g = 3.2 and 3.3 ± 0.6), followed by 4F-M[¹⁸F]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[¹⁸F]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[¹⁸F]FES, M-[¹⁸F]FES and [¹⁸F]FES) had more favourable target tissue uptake and target-to-background ratios. [ABSTRACT FROM AUTHOR]