title: Quantification of 18F-fluorocholine kinetics in patients with prostate cancer.
abstract: Choline kinase is upregulated in prostate cancer, resulting in increased (18)F-fluoromethylcholine uptake. This study used pharmacokinetic modeling to validate the use of simplified methods for quantification of (18)F-fluoromethylcholine uptake in a routine clinical setting.
  
  
  METHODS
  Forty-minute dynamic PET/CT scans were acquired after injection of 204 ± 9 MBq of (18)F-fluoromethylcholine, from 8 patients with histologically proven metastasized prostate cancer. Plasma input functions were obtained using continuous arterial blood-sampling as well as using image-derived methods. Manual arterial blood samples were used for calibration and correction for plasma-to-blood ratio and metabolites. Time-activity curves were derived from volumes of interest in all visually detectable lymph node metastases. (18)F-fluoromethylcholine kinetics were studied by nonlinear regression fitting of several single- and 2-tissue plasma input models to the time-activity curves. Model selection was based on the Akaike information criterion and measures of robustness. In addition, the performance of several simplified methods, such as standardized uptake value (SUV), was assessed.
  
  
  RESULTS
  Best fits were obtained using an irreversible compartment model with blood volume parameter. Parent fractions were 0.12 ± 0.4 after 20 min, necessitating individual metabolite corrections. Correspondence between venous and arterial parent fractions was low as determined by the intraclass correlation coefficient (0.61). Results for image-derived input functions that were obtained from volumes of interest in blood-pool structures distant from tissues of high (18)F-fluoromethylcholine uptake yielded good correlation to those for the blood-sampling input functions (R(2) = 0.83). SUV showed poor correlation to parameters derived from full quantitative kinetic analysis (R(2) < 0.34). In contrast, lesion activity concentration normalized to the integral of the blood activity concentration over time (SUVAUC) showed good correlation (R(2) = 0.92 for metabolite-corrected plasma; 0.65 for whole-blood activity concentrations).
  
  
  CONCLUSIONS
  SUV cannot be used to quantify (18)F-fluoromethylcholine uptake. A clinical compromise could be SUVAUC derived from 2 consecutive static PET scans, one centered on a large blood-pool structure during 0-30 min after injection to obtain the blood activity concentrations and the other a whole-body scan at 30 min after injection to obtain lymph node activity concentrations.
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands e.verwer@vumc.nl.
authors: Eline E
authors: EE
authors: Verwer
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Daniela E
authors: DE
authors: Oprea-Lager
authors: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Alfons J M
authors: AJ
authors: van den Eertwegh
authors: Department of Urology, VU University Medical Center, Amsterdam, The Netherlands; and.
authors: Reindert J A
authors: RJ
authors: van Moorselaar
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Albert D
authors: AD
authors: Windhorst
authors: Department of Anesthesiology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Lothar A
authors: LA
authors: Schwarte
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: N Harry
authors: NH
authors: Hendrikse
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Robert C
authors: RC
authors: Schuit
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Otto S
authors: OS
authors: Hoekstra
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Adriaan A
authors: AA
authors: Lammertsma
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Ronald
authors: R
authors: Boellaard
mesh_terms: D000368:Aged; D002138:Calibration; D002794:Choline / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008198:Lymph Nodes / Q000000981:diagnostic imaging; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging*; D019275:Radiopharmaceuticals / Q000737:chemistry; D012044:Regression Analysis; D013997:Time Factors; D014057:Tomography, X-Ray Computed
chemical_list: D019275:Radiopharmaceuticals; C516370:fluoromethylcholine; C514960:fluorocholine; D002794:Choline
keywords: choline; positron emission tomography (PET); prostate cancer; standardized uptake value (SUV); tracer kinetic modeling