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Erschienen in:
01.08.2008 | Original Article
[18F]Fluorinated estradiol derivatives for oestrogen receptor imaging: impact of substituents, formulation and specific activity on the biodistribution in breast tumour-bearing mice
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 8/2008
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Purpose
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.
Methods
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.
Results
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.
Conclusion
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.