TY - JOUR
T1 - Improved detection and measurement of low levels of [ 18F]fluoride metabolized from [ 18F]-labeled pyrimidine nucleoside analogues in biological samples
AU - Paolillo, Vincenzo
AU - Yeh, Hsin Hsien
AU - Mukhopadhyay, Uday
AU - Gelovani, Juri G.
AU - Alauddin, Mian M.
N1 - Funding Information:
This work was supported by start-up funds from The University of Texas M.D. Anderson Cancer Center to Drs. Mian M. Alauddin and Juri G. Gelovani and the NCI CCSG Core Grant CA 106672 .
PY - 2011/11
Y1 - 2011/11
N2 - Introduction: It is important to identify all circulating metabolites, including free fluoride, for accurate pharmacokinetic modeling of [ 18F]-labeled radiotracers. We sought to determine the most efficient method to detect and quantify low levels of free [ 18F]fluoride in biological samples. Methods: Low levels of [ 18F]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 [ 18F]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. [ 18F]Fluoride was also determined in plasma and urine from mice injected with [ 18F]-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, [ 18F]fluoride was determined in plasma for [ 18F]FLT, [ 18F]FMAU, [ 18F]FEAU and N 3-[ 18F]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 [ 18F]fluoride determined in the urine was 11.49±1.60% (n=4) from [ 18F]FLT, 5.36±2.34% (n=3) from [ 18F]FMAU, 13.57±1.96% (n=3) from [ 18F]FEAU and 11.19±1.98% (n=4) from N 3-[ 18F]FPrT. Conclusion: Low levels of [ 18F]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 [ 18F]-labeled radiotracer and PET.
AB - Introduction: It is important to identify all circulating metabolites, including free fluoride, for accurate pharmacokinetic modeling of [ 18F]-labeled radiotracers. We sought to determine the most efficient method to detect and quantify low levels of free [ 18F]fluoride in biological samples. Methods: Low levels of [ 18F]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 [ 18F]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. [ 18F]Fluoride was also determined in plasma and urine from mice injected with [ 18F]-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, [ 18F]fluoride was determined in plasma for [ 18F]FLT, [ 18F]FMAU, [ 18F]FEAU and N 3-[ 18F]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 [ 18F]fluoride determined in the urine was 11.49±1.60% (n=4) from [ 18F]FLT, 5.36±2.34% (n=3) from [ 18F]FMAU, 13.57±1.96% (n=3) from [ 18F]FEAU and 11.19±1.98% (n=4) from N 3-[ 18F]FPrT. Conclusion: Low levels of [ 18F]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 [ 18F]-labeled radiotracer and PET.
KW - Ion exchange cartridge
KW - PET
KW - Radiopharmaceuticals
KW - [ F]Fluoride
UR - http://www.scopus.com/inward/record.url?scp=82655172516&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=82655172516&partnerID=8YFLogxK
U2 - 10.1016/j.nucmedbio.2011.05.008
DO - 10.1016/j.nucmedbio.2011.05.008
M3 - Article
C2 - 21741850
AN - SCOPUS:82655172516
SN - 0969-8051
VL - 38
SP - 1129
EP - 1134
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
IS - 8
ER -