Abstract

Radiolabeled Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) has demonstrated promising results for prostate cancer (PCa) imaging. Quantification of PSMA radiotracer uptake is desired as it enables reliable interpretation of PET-images, the use of PSMA uptake as an imaging biomarker for tumor characterization, and evaluation of treatment effects. The aim of this study was to perform a full pharmacokinetic analysis of 18F-DCFPyL, a second generation 18F-labeled PSMA ligand. Based on the pharmacokinetic analysis (reference method), simplified methods for quantification of 18F-DCFPyL uptake were validated. Methods: Eight patients with metastasized PCa were included. Dynamic PET acquisitions were performed from 0-60 and 90-120 min after injection of a median dose of 313MBq 18F-DCFPyL (range 292-314 MBq). Continuous and manual arterial blood sampling provided calibrated plasma tracer input functions. Time-activity curves were derived for each PCa metastasis and 18F-DCFPyL kinetics were described using standard plasma input tissue-compartment models. Simplified methods for quantification of 18F-DCFPyL uptake (Standardized Uptake Values [SUV]; Tumor-to-Blood Ratios [TBR]) were correlated with kinetic parameter estimates obtained from full pharmacokinetic analysis. Results:N = 46 metastases were evaluated. A reversible two-tissue compartment model was the preferred model for 18F-DCFPyL kinetics in 59% of the metastases. The observed k4 was small, however, resulting in nearly irreversible kinetics during the course of the PET study. Hence, k4 was fixated (0.015) and Ki was preferred as the reference kinetic parameter. Whole-blood TBR provided excellent correlation with Ki from full kinetic analysis (R2=0.97). This TBR could be simplified further by replacing the blood samples with an image-based, single measurement of blood activity in the aorta ascendens (image-based TBR, R¬2=0.96). SUV correlated poorly with Ki (R¬2 =0.47 and R¬2=0.60 for SUV normalized to body weight and lean-body mass, respectively), most likely due to deviant blood activity concentrations (i.e. tumor tracer input) in patients with higher tumor volumes. Conclusion:18F-DCFPyL kinetics in PCa metastases are best described by a reversible two-tissue compartment model. Image-based Tumor-to-Blood ratios were validated as a simplified method to quantify 18F-DCFPyL uptake and might be applied to clinical, whole-body PET scans. SUV does not provide reliable quantification of 18F-DCFPyL uptake.

LanguageEnglish
Pagesjnumed.119.227520
JournalJournal of Nuclear Medicine
Early online date18 Apr 2019
DOIs
Publication statusPublished - 19 Apr 2019

Cite this

@article{04864f48b7ea4afbac974bb940dff039,
title = "Simplified Methods for Quantification of 18F-DCFPyL Uptake in Patients with Prostate Cancer",
abstract = "Radiolabeled Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) has demonstrated promising results for prostate cancer (PCa) imaging. Quantification of PSMA radiotracer uptake is desired as it enables reliable interpretation of PET-images, the use of PSMA uptake as an imaging biomarker for tumor characterization, and evaluation of treatment effects. The aim of this study was to perform a full pharmacokinetic analysis of 18F-DCFPyL, a second generation 18F-labeled PSMA ligand. Based on the pharmacokinetic analysis (reference method), simplified methods for quantification of 18F-DCFPyL uptake were validated. Methods: Eight patients with metastasized PCa were included. Dynamic PET acquisitions were performed from 0-60 and 90-120 min after injection of a median dose of 313MBq 18F-DCFPyL (range 292-314 MBq). Continuous and manual arterial blood sampling provided calibrated plasma tracer input functions. Time-activity curves were derived for each PCa metastasis and 18F-DCFPyL kinetics were described using standard plasma input tissue-compartment models. Simplified methods for quantification of 18F-DCFPyL uptake (Standardized Uptake Values [SUV]; Tumor-to-Blood Ratios [TBR]) were correlated with kinetic parameter estimates obtained from full pharmacokinetic analysis. Results:N = 46 metastases were evaluated. A reversible two-tissue compartment model was the preferred model for 18F-DCFPyL kinetics in 59{\%} of the metastases. The observed k4 was small, however, resulting in nearly irreversible kinetics during the course of the PET study. Hence, k4 was fixated (0.015) and Ki was preferred as the reference kinetic parameter. Whole-blood TBR provided excellent correlation with Ki from full kinetic analysis (R2=0.97). This TBR could be simplified further by replacing the blood samples with an image-based, single measurement of blood activity in the aorta ascendens (image-based TBR, R¬2=0.96). SUV correlated poorly with Ki (R¬2 =0.47 and R¬2=0.60 for SUV normalized to body weight and lean-body mass, respectively), most likely due to deviant blood activity concentrations (i.e. tumor tracer input) in patients with higher tumor volumes. Conclusion:18F-DCFPyL kinetics in PCa metastases are best described by a reversible two-tissue compartment model. Image-based Tumor-to-Blood ratios were validated as a simplified method to quantify 18F-DCFPyL uptake and might be applied to clinical, whole-body PET scans. SUV does not provide reliable quantification of 18F-DCFPyL uptake.",
author = "Jansen, {Bernard H E} and Maqsood Yaqub and Jens Voortman and Cysouw, {Matthijs C F} and Windhorst, {Albert D} and Schuit, {Robert C} and Kramer, {Gerbrand M} and {van den Eertwegh}, {Alfons J M} and Schwarte, {Lothar A} and Hendrikse, {Harry N} and Vis, {Andr{\'e} N} and {van Moorselaar}, {Reindert J A} and Hoekstra, {Otto S} and Ronald Boellaard and Oprea-Lager, {Daniela E}",
note = "Copyright {\circledC} 2019 by the Society of Nuclear Medicine and Molecular Imaging, Inc.",
year = "2019",
month = "4",
day = "19",
doi = "10.2967/jnumed.119.227520",
language = "English",
pages = "jnumed.119.227520",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",

}

TY - JOUR

T1 - Simplified Methods for Quantification of 18F-DCFPyL Uptake in Patients with Prostate Cancer

AU - Jansen, Bernard H E

AU - Yaqub, Maqsood

AU - Voortman, Jens

AU - Cysouw, Matthijs C F

AU - Windhorst, Albert D

AU - Schuit, Robert C

AU - Kramer, Gerbrand M

AU - van den Eertwegh, Alfons J M

AU - Schwarte, Lothar A

AU - Hendrikse, Harry N

AU - Vis, André N

AU - van Moorselaar, Reindert J A

AU - Hoekstra, Otto S

AU - Boellaard, Ronald

AU - Oprea-Lager, Daniela E

N1 - Copyright © 2019 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

PY - 2019/4/19

Y1 - 2019/4/19

N2 - Radiolabeled Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) has demonstrated promising results for prostate cancer (PCa) imaging. Quantification of PSMA radiotracer uptake is desired as it enables reliable interpretation of PET-images, the use of PSMA uptake as an imaging biomarker for tumor characterization, and evaluation of treatment effects. The aim of this study was to perform a full pharmacokinetic analysis of 18F-DCFPyL, a second generation 18F-labeled PSMA ligand. Based on the pharmacokinetic analysis (reference method), simplified methods for quantification of 18F-DCFPyL uptake were validated. Methods: Eight patients with metastasized PCa were included. Dynamic PET acquisitions were performed from 0-60 and 90-120 min after injection of a median dose of 313MBq 18F-DCFPyL (range 292-314 MBq). Continuous and manual arterial blood sampling provided calibrated plasma tracer input functions. Time-activity curves were derived for each PCa metastasis and 18F-DCFPyL kinetics were described using standard plasma input tissue-compartment models. Simplified methods for quantification of 18F-DCFPyL uptake (Standardized Uptake Values [SUV]; Tumor-to-Blood Ratios [TBR]) were correlated with kinetic parameter estimates obtained from full pharmacokinetic analysis. Results:N = 46 metastases were evaluated. A reversible two-tissue compartment model was the preferred model for 18F-DCFPyL kinetics in 59% of the metastases. The observed k4 was small, however, resulting in nearly irreversible kinetics during the course of the PET study. Hence, k4 was fixated (0.015) and Ki was preferred as the reference kinetic parameter. Whole-blood TBR provided excellent correlation with Ki from full kinetic analysis (R2=0.97). This TBR could be simplified further by replacing the blood samples with an image-based, single measurement of blood activity in the aorta ascendens (image-based TBR, R¬2=0.96). SUV correlated poorly with Ki (R¬2 =0.47 and R¬2=0.60 for SUV normalized to body weight and lean-body mass, respectively), most likely due to deviant blood activity concentrations (i.e. tumor tracer input) in patients with higher tumor volumes. Conclusion:18F-DCFPyL kinetics in PCa metastases are best described by a reversible two-tissue compartment model. Image-based Tumor-to-Blood ratios were validated as a simplified method to quantify 18F-DCFPyL uptake and might be applied to clinical, whole-body PET scans. SUV does not provide reliable quantification of 18F-DCFPyL uptake.

AB - Radiolabeled Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) has demonstrated promising results for prostate cancer (PCa) imaging. Quantification of PSMA radiotracer uptake is desired as it enables reliable interpretation of PET-images, the use of PSMA uptake as an imaging biomarker for tumor characterization, and evaluation of treatment effects. The aim of this study was to perform a full pharmacokinetic analysis of 18F-DCFPyL, a second generation 18F-labeled PSMA ligand. Based on the pharmacokinetic analysis (reference method), simplified methods for quantification of 18F-DCFPyL uptake were validated. Methods: Eight patients with metastasized PCa were included. Dynamic PET acquisitions were performed from 0-60 and 90-120 min after injection of a median dose of 313MBq 18F-DCFPyL (range 292-314 MBq). Continuous and manual arterial blood sampling provided calibrated plasma tracer input functions. Time-activity curves were derived for each PCa metastasis and 18F-DCFPyL kinetics were described using standard plasma input tissue-compartment models. Simplified methods for quantification of 18F-DCFPyL uptake (Standardized Uptake Values [SUV]; Tumor-to-Blood Ratios [TBR]) were correlated with kinetic parameter estimates obtained from full pharmacokinetic analysis. Results:N = 46 metastases were evaluated. A reversible two-tissue compartment model was the preferred model for 18F-DCFPyL kinetics in 59% of the metastases. The observed k4 was small, however, resulting in nearly irreversible kinetics during the course of the PET study. Hence, k4 was fixated (0.015) and Ki was preferred as the reference kinetic parameter. Whole-blood TBR provided excellent correlation with Ki from full kinetic analysis (R2=0.97). This TBR could be simplified further by replacing the blood samples with an image-based, single measurement of blood activity in the aorta ascendens (image-based TBR, R¬2=0.96). SUV correlated poorly with Ki (R¬2 =0.47 and R¬2=0.60 for SUV normalized to body weight and lean-body mass, respectively), most likely due to deviant blood activity concentrations (i.e. tumor tracer input) in patients with higher tumor volumes. Conclusion:18F-DCFPyL kinetics in PCa metastases are best described by a reversible two-tissue compartment model. Image-based Tumor-to-Blood ratios were validated as a simplified method to quantify 18F-DCFPyL uptake and might be applied to clinical, whole-body PET scans. SUV does not provide reliable quantification of 18F-DCFPyL uptake.

UR - http://www.mendeley.com/research/simplified-methods-quantification-18-fdcfpyl-uptake-patients-prostate-cancer

U2 - 10.2967/jnumed.119.227520

DO - 10.2967/jnumed.119.227520

M3 - Article

SP - jnumed.119.227520

JO - Journal of Nuclear Medicine

T2 - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

ER -