title: [18F]Fluorinated estradiol derivatives for oestrogen receptor imaging: impact of substituents, formulation and specific activity on the biodistribution in breast tumour-bearing mice.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Sherbrooke Molecular Imaging Center, Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC, Canada, J1H 5N4. Francois.Benard@USherbrooke.ca
authors: François
authors: F
authors: Bénard
authors: Naseem
authors: N
authors: Ahmed
authors: Jean-Mathieu
authors: JM
authors: Beauregard
authors: Jacques
authors: J
authors: Rousseau
authors: Antonio
authors: A
authors: Aliaga
authors: Céléna
authors: C
authors: Dubuc
authors: Etienne
authors: E
authors: Croteau
authors: Johan E
authors: JE
authors: van Lier
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011960:Receptors, Estrogen / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D019275:Radiopharmaceuticals; D011960:Receptors, Estrogen; C037810:4-fluoroestradiol; D004958:Estradiol