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Quantitative (18)F-fluorocholine positron emission tomography for prostate cancer: correlation between kinetic parameters and Gleason scoring

BACKGROUND: The use of radiolabeled choline as a positron emission tomography (PET) agent for imaging primary tumors in the prostate has been evaluated extensively over the past two decades. There are, however, conflicting reports of its sensitivity and the relationship between choline PET imaging a...

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Autores principales: Schaefferkoetter, Joshua D., Wang, Ziting, Stephenson, Mary C., Roy, Sharmili, Conti, Maurizio, Eriksson, Lars, Townsend, David W., Thamboo, Thomas, Chiong, Edmund
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360745/
https://www.ncbi.nlm.nih.gov/pubmed/28324340
http://dx.doi.org/10.1186/s13550-017-0269-0
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author Schaefferkoetter, Joshua D.
Wang, Ziting
Stephenson, Mary C.
Roy, Sharmili
Conti, Maurizio
Eriksson, Lars
Townsend, David W.
Thamboo, Thomas
Chiong, Edmund
author_facet Schaefferkoetter, Joshua D.
Wang, Ziting
Stephenson, Mary C.
Roy, Sharmili
Conti, Maurizio
Eriksson, Lars
Townsend, David W.
Thamboo, Thomas
Chiong, Edmund
author_sort Schaefferkoetter, Joshua D.
collection PubMed
description BACKGROUND: The use of radiolabeled choline as a positron emission tomography (PET) agent for imaging primary tumors in the prostate has been evaluated extensively over the past two decades. There are, however, conflicting reports of its sensitivity and the relationship between choline PET imaging and disease staging is not fully understood. Moreover, relatively few studies have investigated the correlation between tracer uptake and histological tumor grade. This work quantified (18)F-fluorocholine in tumor and healthy prostate tissue using pharmacokinetic modeling and stratified uptake parameters by histology grade. Additionally, the effect of scan time on the estimation of the kinetic exchange rate constants was evaluated, and the tracer influx parameters from full compartmental analysis were compared to uptake values quantified by Patlak and standardized uptake value (SUV) analyses. (18)F-fluorocholine was administered as a 222 MBq bolus injection to ten patients with biopsy-confirmed prostate tumors, and dynamic PET data were acquired for 60 min. Image-derived arterial input functions were scaled by discrete blood samples, and a 2-tissue, 4-parameter model accounting for blood volume (2T4k+Vb) was used to perform fully quantitative compartmental modeling on tumor, healthy prostate, and muscle tissue. Subsequently, all patients underwent radical prostatectomy, and histological analyses were performed on the prostate specimens; kinetic parameters for tumors were stratified by Gleason score. Correlations were investigated between compartmental K (1) and K (i) parameters and SUV and Patlak slope; the effect of scan time on parameter bias was also evaluated. RESULTS: Choline activity curves in seven tumors, eight healthy prostate regions, and nine muscle regions were analyzed. Net tracer influx was generally higher in tumor relative to healthy prostate, with the values in the highest grade tumors markedly higher than those in lower grade tumors. Influx terms from Patlak and full compartmental modeling showed good correlation within individual tissue groups. Kinetic parameters calculated from the entire 60-min scan data were accurately reproduced from the first 30 min of acquired data (R (2) ≈ 0.9). CONCLUSIONS: Strong correlations were observed between K (i) and Patlak slope in tumor tissue, and K (1) and SUV were also correlated but to a lesser degree. Reliable estimates of all kinetic parameters can be achieved from the first 30 min of dynamic (18)F-choline data. Although SUV, K (1), K (i), and Patlak slope were found to be poor differentiators of low-grade tumor compared to healthy prostate tissue, they are strong indicators of aggressive disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13550-017-0269-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-53607452017-04-06 Quantitative (18)F-fluorocholine positron emission tomography for prostate cancer: correlation between kinetic parameters and Gleason scoring Schaefferkoetter, Joshua D. Wang, Ziting Stephenson, Mary C. Roy, Sharmili Conti, Maurizio Eriksson, Lars Townsend, David W. Thamboo, Thomas Chiong, Edmund EJNMMI Res Original Research BACKGROUND: The use of radiolabeled choline as a positron emission tomography (PET) agent for imaging primary tumors in the prostate has been evaluated extensively over the past two decades. There are, however, conflicting reports of its sensitivity and the relationship between choline PET imaging and disease staging is not fully understood. Moreover, relatively few studies have investigated the correlation between tracer uptake and histological tumor grade. This work quantified (18)F-fluorocholine in tumor and healthy prostate tissue using pharmacokinetic modeling and stratified uptake parameters by histology grade. Additionally, the effect of scan time on the estimation of the kinetic exchange rate constants was evaluated, and the tracer influx parameters from full compartmental analysis were compared to uptake values quantified by Patlak and standardized uptake value (SUV) analyses. (18)F-fluorocholine was administered as a 222 MBq bolus injection to ten patients with biopsy-confirmed prostate tumors, and dynamic PET data were acquired for 60 min. Image-derived arterial input functions were scaled by discrete blood samples, and a 2-tissue, 4-parameter model accounting for blood volume (2T4k+Vb) was used to perform fully quantitative compartmental modeling on tumor, healthy prostate, and muscle tissue. Subsequently, all patients underwent radical prostatectomy, and histological analyses were performed on the prostate specimens; kinetic parameters for tumors were stratified by Gleason score. Correlations were investigated between compartmental K (1) and K (i) parameters and SUV and Patlak slope; the effect of scan time on parameter bias was also evaluated. RESULTS: Choline activity curves in seven tumors, eight healthy prostate regions, and nine muscle regions were analyzed. Net tracer influx was generally higher in tumor relative to healthy prostate, with the values in the highest grade tumors markedly higher than those in lower grade tumors. Influx terms from Patlak and full compartmental modeling showed good correlation within individual tissue groups. Kinetic parameters calculated from the entire 60-min scan data were accurately reproduced from the first 30 min of acquired data (R (2) ≈ 0.9). CONCLUSIONS: Strong correlations were observed between K (i) and Patlak slope in tumor tissue, and K (1) and SUV were also correlated but to a lesser degree. Reliable estimates of all kinetic parameters can be achieved from the first 30 min of dynamic (18)F-choline data. Although SUV, K (1), K (i), and Patlak slope were found to be poor differentiators of low-grade tumor compared to healthy prostate tissue, they are strong indicators of aggressive disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13550-017-0269-0) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2017-03-21 /pmc/articles/PMC5360745/ /pubmed/28324340 http://dx.doi.org/10.1186/s13550-017-0269-0 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Research
Schaefferkoetter, Joshua D.
Wang, Ziting
Stephenson, Mary C.
Roy, Sharmili
Conti, Maurizio
Eriksson, Lars
Townsend, David W.
Thamboo, Thomas
Chiong, Edmund
Quantitative (18)F-fluorocholine positron emission tomography for prostate cancer: correlation between kinetic parameters and Gleason scoring
title Quantitative (18)F-fluorocholine positron emission tomography for prostate cancer: correlation between kinetic parameters and Gleason scoring
title_full Quantitative (18)F-fluorocholine positron emission tomography for prostate cancer: correlation between kinetic parameters and Gleason scoring
title_fullStr Quantitative (18)F-fluorocholine positron emission tomography for prostate cancer: correlation between kinetic parameters and Gleason scoring
title_full_unstemmed Quantitative (18)F-fluorocholine positron emission tomography for prostate cancer: correlation between kinetic parameters and Gleason scoring
title_short Quantitative (18)F-fluorocholine positron emission tomography for prostate cancer: correlation between kinetic parameters and Gleason scoring
title_sort quantitative (18)f-fluorocholine positron emission tomography for prostate cancer: correlation between kinetic parameters and gleason scoring
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360745/
https://www.ncbi.nlm.nih.gov/pubmed/28324340
http://dx.doi.org/10.1186/s13550-017-0269-0
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