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Original research
Ting-Yim Lee
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7605-9752
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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 FFAZA and 18 FFEPPA , for imaging hypoxia and inflammation respectively.
Results
Radioactivity as low as 17Bq in 2µL 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 inter-subject and intra-subject variability in radio-metabolites production could be observed with both tracers. For 18 FFEPPA, 50% of plasma activity was from radio-metabolites as early as 5 min post injection while for 18 FFAZA, 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.
Keywords
[18F]FEPPA, [18F]FAZA, Radio-metabolite Correction, Thin Layer Chromatography (TLC), Dynamic PET, Autoradiography
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CURRENT STATUS: Published
View the published article at EJNMMI Research.
Version 3
Posted 11 Sep, 2020
No community comments so far
Editorial decision: Accept
On 09 Sep, 2020
Editor assigned
On 09 Sep, 2020
Submission checks complete
On 08 Sep, 2020
Editor invited
On 08 Sep, 2020
No comments provided
Reviewers invited
Invitations sent on 29 Aug, 2020
Reviewer #1 agreed
On 29 Aug, 2020
Editor assigned
On 28 Aug, 2020
Submission checks complete
On 27 Aug, 2020
Editor invited
On 27 Aug, 2020
No comments provided
Review #1 received
Received 21 Jul, 2020
Editorial decision: Major Revision
On 21 Jul, 2020
Review #2 received
Received 18 Jul, 2020
Reviewer #2 agreed
On 08 Jul, 2020
Reviewer #1 agreed
On 04 Jul, 2020
Reviewers invited
Invitations sent on 03 Jul, 2020
Editor assigned
On 29 Jun, 2020
Editor invited
On 28 Jun, 2020
Submission checks complete
On 17 Jun, 2020
First submitted
On 12 Jun, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cellular Metabolism
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A new preprint design is coming!
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See the published version of this preprint at EJNMMI Research.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Original research
Ting-Yim Lee
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7605-9752
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at EJNMMI Research.
Version 3
Posted 11 Sep, 2020
No community comments so far
Editorial decision: Accept
On 09 Sep, 2020
Editor assigned
On 09 Sep, 2020
Submission checks complete
On 08 Sep, 2020
Editor invited
On 08 Sep, 2020
No comments provided
Reviewers invited
Invitations sent on 29 Aug, 2020
Reviewer #1 agreed
On 29 Aug, 2020
Editor assigned
On 28 Aug, 2020
Submission checks complete
On 27 Aug, 2020
Editor invited
On 27 Aug, 2020
No comments provided
Review #1 received
Received 21 Jul, 2020
Editorial decision: Major Revision
On 21 Jul, 2020
Review #2 received
Received 18 Jul, 2020
Reviewer #2 agreed
On 08 Jul, 2020
Reviewer #1 agreed
On 04 Jul, 2020
Reviewers invited
Invitations sent on 03 Jul, 2020
Editor assigned
On 29 Jun, 2020
Editor invited
On 28 Jun, 2020
Submission checks complete
On 17 Jun, 2020
First submitted
On 12 Jun, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cellular Metabolism
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at EJNMMI 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 FFAZA and 18 FFEPPA , for imaging hypoxia and inflammation respectively.
Results
Radioactivity as low as 17Bq in 2µL 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 inter-subject and intra-subject variability in radio-metabolites production could be observed with both tracers. For 18 FFEPPA, 50% of plasma activity was from radio-metabolites as early as 5 min post injection while for 18 FFAZA, 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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
The full text of this article is available to read as a PDF.
This is a list of supplementary files associated with this preprint. Click to download.
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