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Plasma radio-metabolite analysis of PET tracers for dynamic PET imaging: TLC and autoradiography
BACKGROUND: In molecular imaging with dynamic PET, the binding and dissociation of a targeted tracer is characterized by kinetics modeling which requires the arterial concentration of the tracer to be measured accurately. Once in the body the radiolabeled parent tracer may be subjected to hydrolysis...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683627/ https://www.ncbi.nlm.nih.gov/pubmed/33226509 http://dx.doi.org/10.1186/s13550-020-00705-2 |
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author | Li, Fiona Hicks, Justin W. Yu, Lihai Desjardin, Lise Morrison, Laura Hadway, Jennifer Lee, Ting-Yim |
author_facet | Li, Fiona Hicks, Justin W. Yu, Lihai Desjardin, Lise Morrison, Laura Hadway, Jennifer Lee, Ting-Yim |
author_sort | Li, Fiona |
collection | PubMed |
description | BACKGROUND: In molecular imaging with dynamic PET, the binding and dissociation of a targeted tracer is characterized by kinetics modeling which requires the arterial concentration of the tracer to be measured accurately. Once in the body the radiolabeled parent tracer may be subjected to hydrolysis, demethylation/dealkylation and other biochemical processes, resulting in the production and accumulation of different metabolites in blood which can be labeled with the same PET radionuclide as the parent. Since these radio-metabolites cannot be distinguished by PET scanning from the parent tracer, their contribution to the arterial concentration curve has to be removed for the accurate estimation of kinetic parameters from kinetic analysis of dynamic PET. High-performance liquid chromatography has been used to separate and measure radio-metabolites in blood plasma; however, the method is labor intensive and remains a challenge to implement for each individual patient. The purpose of this study is to develop an alternate technique based on thin layer chromatography (TLC) and a sensitive commercial autoradiography system (Beaver, Ai4R, Nantes, France) to measure radio-metabolites in blood plasma of two targeted tracers—[(18)F]FAZA and [(18)F]FEPPA, for imaging hypoxia and inflammation, respectively. RESULTS: Radioactivity as low as 17 Bq in 2 µL of pig’s plasma can be detected on the TLC plate using autoradiography. Peaks corresponding to the parent tracer and radio-metabolites could be distinguished in the line profile through each sample (n = 8) in the autoradiographic image. Significant intersubject and intra-subject variability in radio-metabolites production could be observed with both tracers. For [(18)F]FEPPA, 50% of plasma activity was from radio-metabolites as early as 5-min post injection, while for [(18)F]FAZA, significant metabolites did not appear until 50-min post. Simulation study investigating the effect of radio-metabolite in the estimation of kinetic parameters indicated that 32–400% parameter error can result without radio-metabolites correction. CONCLUSION: TLC coupled with autoradiography is a good alternative to high-performance liquid chromatography for radio-metabolite correction. The advantages of requiring only small blood samples (~ 100 μL) and of analyzing multiple samples simultaneously, make the method suitable for individual dynamic PET studies. |
format | Online Article Text |
id | pubmed-7683627 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-76836272020-11-27 Plasma radio-metabolite analysis of PET tracers for dynamic PET imaging: TLC and autoradiography Li, Fiona Hicks, Justin W. Yu, Lihai Desjardin, Lise Morrison, Laura Hadway, Jennifer Lee, Ting-Yim EJNMMI Res Original Research BACKGROUND: In molecular imaging with dynamic PET, the binding and dissociation of a targeted tracer is characterized by kinetics modeling which requires the arterial concentration of the tracer to be measured accurately. Once in the body the radiolabeled parent tracer may be subjected to hydrolysis, demethylation/dealkylation and other biochemical processes, resulting in the production and accumulation of different metabolites in blood which can be labeled with the same PET radionuclide as the parent. Since these radio-metabolites cannot be distinguished by PET scanning from the parent tracer, their contribution to the arterial concentration curve has to be removed for the accurate estimation of kinetic parameters from kinetic analysis of dynamic PET. High-performance liquid chromatography has been used to separate and measure radio-metabolites in blood plasma; however, the method is labor intensive and remains a challenge to implement for each individual patient. The purpose of this study is to develop an alternate technique based on thin layer chromatography (TLC) and a sensitive commercial autoradiography system (Beaver, Ai4R, Nantes, France) to measure radio-metabolites in blood plasma of two targeted tracers—[(18)F]FAZA and [(18)F]FEPPA, for imaging hypoxia and inflammation, respectively. RESULTS: Radioactivity as low as 17 Bq in 2 µL of pig’s plasma can be detected on the TLC plate using autoradiography. Peaks corresponding to the parent tracer and radio-metabolites could be distinguished in the line profile through each sample (n = 8) in the autoradiographic image. Significant intersubject and intra-subject variability in radio-metabolites production could be observed with both tracers. For [(18)F]FEPPA, 50% of plasma activity was from radio-metabolites as early as 5-min post injection, while for [(18)F]FAZA, significant metabolites did not appear until 50-min post. Simulation study investigating the effect of radio-metabolite in the estimation of kinetic parameters indicated that 32–400% parameter error can result without radio-metabolites correction. CONCLUSION: TLC coupled with autoradiography is a good alternative to high-performance liquid chromatography for radio-metabolite correction. The advantages of requiring only small blood samples (~ 100 μL) and of analyzing multiple samples simultaneously, make the method suitable for individual dynamic PET studies. Springer Berlin Heidelberg 2020-11-23 /pmc/articles/PMC7683627/ /pubmed/33226509 http://dx.doi.org/10.1186/s13550-020-00705-2 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Original Research Li, Fiona Hicks, Justin W. Yu, Lihai Desjardin, Lise Morrison, Laura Hadway, Jennifer Lee, Ting-Yim Plasma radio-metabolite analysis of PET tracers for dynamic PET imaging: TLC and autoradiography |
title | Plasma radio-metabolite analysis of PET tracers for dynamic PET imaging: TLC and autoradiography |
title_full | Plasma radio-metabolite analysis of PET tracers for dynamic PET imaging: TLC and autoradiography |
title_fullStr | Plasma radio-metabolite analysis of PET tracers for dynamic PET imaging: TLC and autoradiography |
title_full_unstemmed | Plasma radio-metabolite analysis of PET tracers for dynamic PET imaging: TLC and autoradiography |
title_short | Plasma radio-metabolite analysis of PET tracers for dynamic PET imaging: TLC and autoradiography |
title_sort | plasma radio-metabolite analysis of pet tracers for dynamic pet imaging: tlc and autoradiography |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683627/ https://www.ncbi.nlm.nih.gov/pubmed/33226509 http://dx.doi.org/10.1186/s13550-020-00705-2 |
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