Nonlinear compartmental model of 18F-choline

Tavola, Federico; Janzen, Tilman; Giussani, A.; Facchinetti, Davide; Veronese, I.; Uusijärvi-Lizana, Helena; Mattsson, Sören; Hoeschen, Christoph; Cantone, M.C.

doi:10.1016/j.nucmedbio.2011.09.002

Cited by 17 publications

(16 citation statements)

References 17 publications

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“…At 6 time points (5,10,15,20,30, and 40 min after injection), manual arterial blood samples were collected, while the blood sampler operation was briefly paused. In addition, manual venous blood samples were collected at 5, 15, and 30 min after injection.…”

Section: Data Acquisitionmentioning

confidence: 99%

“…To date, 18 F-fluoromethylcholine biodistribution has been assessed with encouraging results (13)(14)(15)(16), but full kinetic analysis has not yet been reported. In the present study, pharmacokinetic modeling of dynamic PET data in combination with arterial blood sampling was used to determine the appropriate plasma input compartment model for 18 F-fluoromethylcholine.…”

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confidence: 99%

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Quantification of ¹⁸F-Fluorocholine Kinetics in Patients with Prostate Cancer

Geest

Metselaar²,

Storm³

2015

J Nucl Med

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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.

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Section: Data Acquisitionmentioning

confidence: 99%

mentioning

confidence: 99%

Quantification of ¹⁸F-Fluorocholine Kinetics in Patients with Prostate Cancer

Geest

Metselaar²,

Storm³

2015

J Nucl Med

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“…Two strategies were pursued to refine the model structure. On the one hand, the possibility of using nonlinear kinetics for some transfer processes was investigated (11). As an alternative, the so-called forcing-function approach (24) was used here: the original simple model structure was split into several independent subsystems.…”

Section: Model Developmentmentioning

confidence: 99%

“…In these investigations, biodistribution and excretion data were collected for up to 4 h after injection of the radiopharmaceutical. Previous human studies with 11 C-or 18 F-choline were limited up to 1 h after administration (3)(4)(5)(6)(7)10).…”

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A Compartmental Model for Biokinetics and Dosimetry of¹⁸F-Choline in Prostate Cancer Patients

Giussani

Janzen²,

Uusijärvi-Lizana³

et al. 2012

J Nucl Med

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PET with 18 F-choline ( 18 F-FCH) is used in the diagnosis of prostate cancer and its recurrences. In this work, biodistribution data from a recent study conducted at Skå ne University Hospital Malmö were used for the development of a biokinetic and dosimetric model. Methods: The biodistribution of 18 F-FCH was followed for 10 patients using PET up to 4 h after administration. Activity concentrations in blood and urine samples were also determined. A compartmental model structure was developed, and values of the model parameters were obtained for each single patient and for a reference patient using a population kinetic approach. Radiation doses to the organs were determined using computational (voxel) phantoms for the determination of the S factors. Results: The model structure consists of a central exchange compartment (blood), 2 compartments each for the liver and kidneys, 1 for spleen, 1 for urinary bladder, and 1 generic compartment accounting for the remaining material. The model can successfully describe the individual patients' data. The parameters showing the greatest interindividual variations are the blood volume (the clearance process is rapid, and early blood data are not available for several patients) and the transfer out from liver (the physical half-life of 18 F is too short to follow this long-term process with the necessary accuracy). The organs receiving the highest doses are the kidneys (reference patient, 0.079 mGy/MBq; individual values, 0.033-0.105 mGy/MBq) and the liver (reference patient, 0.062 mGy/MBq; individual values, 0.036-0.082 mGy/MBq). The dose to the urinary bladder wall of the reference patient varies between 0.017 and 0.030 mGy/MBq, depending on the assumptions on bladder voiding. Conclusion: The model gives a satisfactory description of the biodistribution of 18 F-FCH and realistic estimates of the radiation dose received by the patients.

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Quantification of internal dosimetry in PET patients II: Individualized Monte Carlo‐based dosimetry for [18F]fluorocholine PET

et al. 2021

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Purpose To obtain individualized internal doses with a Monte Carlo (MC) method in patients undergoing diagnostic [18F]FCH‐PET studies and to compare such doses with the MIRD method calculations. Methods A patient cohort of 17 males were imaged after intravenous administration of a mean [18F]FCH activity of 244.3 MBq. The resulting PET/CT images were processed in order to generate individualized input source and geometry files for dose computation with the MC tool GATE. The resulting dose estimates were studied and compared to the MIRD method with two different computational phantoms. Mass correction of the S‐factors was applied when possible. Potential sources of uncertainty were closely examined: the effect of partial body images, urinary bladder emptying, and biokinetic modeling. Results Large differences in doses between our methodology and the MIRD method were found, generally in the range ±25%, and up to ±120% for some cases. The mass scaling showed improvements, especially for non‐walled and high‐uptake tissues. Simulations of the urinary bladder emptying showed negligible effects on doses to other organs, with the exception of the prostate. Dosimetry based on partial PET/CT images (excluding the legs) resulted in an overestimation of mean doses to bone, skin, and remaining tissues, and minor differences in other organs/tissues. Estimated uncertainties associated with the biokinetics of FCH introduce variations of cumulated activities in the range of ±10% in the high‐uptake organs. Conclusions The MC methodology allows for a higher degree of dosimetry individualization than the MIRD methodology, which in some cases leads to important differences in dose values. Dosimetry of FCH‐PET based on a single partial PET study seems viable due to the particular biokinetics of FCH, even though some correction factors may need to be applied to estimate mean skin/bone doses.

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Nonlinear compartmental model of 18F-choline

Cited by 17 publications

References 17 publications

Quantification of ¹⁸F-Fluorocholine Kinetics in Patients with Prostate Cancer

Quantification of ¹⁸F-Fluorocholine Kinetics in Patients with Prostate Cancer

A Compartmental Model for Biokinetics and Dosimetry of¹⁸F-Choline in Prostate Cancer Patients

Quantification of internal dosimetry in PET patients II: Individualized Monte Carlo‐based dosimetry for [18F]fluorocholine PET

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Nonlinear compartmental model of 18F-choline

Cited by 17 publications

References 17 publications

Quantification of 18F-Fluorocholine Kinetics in Patients with Prostate Cancer

Quantification of 18F-Fluorocholine Kinetics in Patients with Prostate Cancer

A Compartmental Model for Biokinetics and Dosimetry of18F-Choline in Prostate Cancer Patients

Quantification of internal dosimetry in PET patients II: Individualized Monte Carlo‐based dosimetry for [18F]fluorocholine PET

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Product

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Quantification of ¹⁸F-Fluorocholine Kinetics in Patients with Prostate Cancer

Quantification of ¹⁸F-Fluorocholine Kinetics in Patients with Prostate Cancer

A Compartmental Model for Biokinetics and Dosimetry of¹⁸F-Choline in Prostate Cancer Patients