title: Improved detection and measurement of low levels of [18F]fluoride metabolized from [18F]-labeled pyrimidine nucleoside analogues in biological samples.
abstract: BACKGROUND
  It is important to identify all circulating metabolites, including free fluoride, for accurate pharmacokinetic modeling of [(18)F]-labeled radiotracers. We sought to determine the most efficient method to detect and quantify low levels of free [(18)F]fluoride in biological samples.
  
  
  METHODS
  Low levels of [(18)F]fluoride were analyzed using two methods: (A) an ion-exchange cartridge and gamma counting, and (B) radio-HPLC, to compare the detection limits of these two analytical methods. Twenty microliters of [(18)F]fluoride solution was loaded onto an ion-exchange cartridge, then eluted with 20% MeCN/water (5 ml) and radioactivity trapped in the cartridge counted on a gamma counter. [(18)F]Fluoride was also determined in plasma and urine from mice injected with [(18)F]-labeled thymidine analogues using Method A.
  
  
  RESULTS
  The detection sensitivity of Method A was 9.4-fold higher than that of Method B (0.075±0.004 vs. 0.71±0.02 nCi). With Method A, [(18)F]fluoride was determined in plasma for [(18)F]FLT, [(18)F]FMAU, [(18)F]FEAU and N(3)-[(18)F]FPrT as 1.4±0.31% (n=4), 0.17±0.49% (n=3), 4.88±1.62% (n=3) and 12.94±0.48% (n=4), respectively. The amount of [(18)F]fluoride determined in the urine was 11.49±1.60% (n=4) from [(18)F]FLT, 5.36±2.34% (n=3) from [(18)F]FMAU, 13.57±1.96% (n=3) from [(18)F]FEAU and 11.19±1.98% (n=4) from N(3)-[(18)F]FPrT.
  
  
  CONCLUSIONS
  Low levels of [(18)F]fluoride in biological samples can be detected and quantified using an ion-exchange cartridge and gamma counting. This methodology is simple, accurate and superior to the standard use of radio-HPLC on a C(18) column for metabolite analysis, and it should be useful in pharmacokinetic modeling for animal imaging studies using an [(18)F]-labeled radiotracer and PET.
authors: Department of Experimental Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors: Vincenzo
authors: V
authors: Paolillo
authors: Hsin Hsien
authors: HH
authors: Yeh
authors: Uday
authors: U
authors: Mukhopadhyay
authors: Juri G
authors: JG
authors: Gelovani
authors: Mian M
authors: MM
authors: Alauddin
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005459:Fluorides / Q000032:analysis*; D005462:Fluorine Radioisotopes / Q000032:analysis*; D007474:Ion Exchange; D051379:Mice; D012680:Sensitivity and Specificity; D014556:Urine / Q000737:chemistry*
chemical_list: D005462:Fluorine Radioisotopes; D005459:Fluorides