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

Abstract

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.

ICRP Publication 128: Radiation Dose to Patients from Radiopharmaceuticals: a Compendium of Current Information Related to Frequently Used Substances

“…Six new patients were later included in the study. In these investigations, biodistribution and excretion data were collected for up to 4 h after injection of the radiopharmaceutical (Janzen et al., 2010; Giussani et al., 2012; Tavola et al., 2012). Previous human studies with 11 C- or 18 F-choline were limited up to 1 h after administration (Roivainen et al., 2000; DeGrado et al., 2002; Schmid et al., 2005; Kwee et al., 2006; Steiner et al., 2009; Sutinen et al, 2004). (C50) The biokinetics of 11 C-choline and 18 F-choline differ due to the different interactions of carbon and fluorine in the organism.…”

Optimal scan time for evaluation of parathyroid adenoma with [18F]-fluorocholine PET/CT

“…There is very limited data in the literature on the kinetics of FCH – all these studies include prostate cancer patients. Giussani et al 27 have developed a model of FCH kinetics based on biodistribution measurements that describes recirculation of radiopharmaceutical from major organs of early uptake (liver, spleen, kidneys) back into the blood pool, which may provide an explanation for late SUV increase in the parathyroid tissue. Tavola et al 28 concluded in their study that the simple linear model cannot adequately describe the kinetics of FCH, due to non-linear kinetics, which is associated with the release of FCH from the organs back into the blood.…”

Suggested pathway to assess radiation safety of 18F-labeled PET tracers for first-in-human studies

“…The dosimetry of [ 18 F]-choline was estimated at 18 µSv/MBq (risk-weighted absorbed dose coefficient) [10] and 34.1 µSv/MBq (EDE) [11]. …”