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 bloodpool structures distant from tissues of high 18 F-fluoromethylcholine uptake yielded good correlation to those for the blood-sampling input functions (R 2 5 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 (SUV AUC ) showed good correlation (R 2 5 0.92 for metabolite-corrected plasma; 0.65 for whole-blood activity concentrations). Conclusion: SUV cannot be used to quantify 18 F-fluoromethylcholine uptake. A clinical compromise could be SUV AUC 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.

Simplified Methods for Quantification of 18F-Fluoromethylcholine Uptake: Is SUVAUC,PP Actually an SUV?

“…This ratio provided an excellent correlation to the uptake rate constant of the full kinetic modeling ( Fig. 6C; SUV AUC,PP 5 14.54 · K 1 1 0.02; R 2 5 0.91) (1).…”

“…We would like to thank Laffon and coworkers for their interest in our paper (1), as well as for their valuable comments and for giving us the opportunity to further clarify our results.…”

“…TO THE EDITOR: Verwer et al (1) recently presented a study aimed at validating the use of simplified methods for quantification of 18 F-fluoromethylcholine uptake in a routine clinical setting of prostate cancer patients. The authors nicely demonstrated that 18 F-fluoromethylcholine uptake should be quantified using full kinetic modeling involving a single-tissue-compartment model with irreversible trapping and a blood volume parameter, in combination with a metabolite-corrected plasma input function based on invasive arterial blood sampling.…”

“…First, because in current practice A L (t) is usually expressed in kBq/mL rather than in Bq/mL, A 0 should then be expressed in kBq/mL instead of in MBq/mL, as indicated in Figure 6C (and in Supplemental Fig. 2C) (1): the corrective factor is 1/1,000. Second, because K 1 is usually expressed in min 21 rather than in s 21 (the axis units in Fig.…”

PET for Therapy Response Assessment in Glioblastoma

“…However, we could not confirm an increased choline transporter-like proteinmediated transport, nor a higher expression of CK in GBs compared to RN. The immediate metabolization of choline raises the question if 18 F-Fluorobetaine attributes to the detected choline signal, and the uptake in RN is influenced by leakage through the damaged BBB and inflammation (93,(98)(99)(100)(101). As such, correlative imaging with MRI is of utmost importance (85).…”