A compartmental model for biokinetics and dosimetry of 18F-choline in prostate cancer patients.

UNLABELLED: 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 Skåne 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.

Nonlinear compartmental model of 18F-choline.

INTRODUCTION: This work develops a compartmental model of (18)F-choline in order to evaluate its biokinetics and so to describe the temporal variation of the radiopharmaceuticals' uptake in and clearance from organs and tissues. METHODS: Ten patients were considered in this study. A commercially available tool for compartmental analysis (SAAM II) was used to model the values of activity concentrations in organs and tissues obtained from PET images or from measurements of collected blood and urine samples. RESULTS: A linear compartmental model of the biokinetics of the radiopharmaceutical was initially developed. It features a central compartment (blood) exchanging with organs. The structure describes explicitly liver, kidneys, spleen, blood and urinary excretion. The linear model tended to overestimate systematically the activity in the liver and in the kidney compartments in the first 20 min post-administration. A nonlinear process of kinetic saturation was considered, according to the typical Michaelis-Menten kinetics. Therefore nonlinear equations were added to describe the flux of (18)F-choline from blood to liver and from blood to kidneys. The nonlinear model showed a tendency for improvement in the description of the activity in liver and kidneys, but not for the urine. CONCLUSIONS: The simple linear model presented is not able to properly describe the biokinetics of (18)F-choline as measured in prostatic cancer patients. The introduction of nonlinear kinetics, although based on physiologically plausible assumptions, resulted in nonsignificant improvements of the model predictive power.

Modelling urinary excretion of molybdenum after oral and intravenous administration of stable tracers.

An extensive study using stable isotopes of molybdenum as tracers was undertaken to investigate intestinal uptake, systemic kinetics and urinary excretion of molybdenum in healthy human volunteers. In total 63 experiments with 17 volunteers were performed administering the tracers in different chemical forms and measuring their concentrations in blood plasma and urine samples by means of activation analysis and mass spectrometry. Molybdenum was eliminated very rapidly from the circulation. The amount eliminated via the renal pathway was observed to be dependent on several factors, such as form and modality of administration and also the total amount of circulating molybdenum. The fact that the urinary excretion patterns diverged significantly from the current predictions of the International Commission on Radiological Protection model might be relevant when using the model for retrospective intake assessments in case of an accident. On the basis of the experimental data, a more realistic compartmental structure has been presented.

Rates of intestinal absorption of molybdenum in humans.

The intestinal absorption of molybdenum in healthy human volunteers has been measured by simultaneous oral and intravenous administration of the stable isotopes 95Mo and 96Mo, and the results were analysed using the convolution integral technique. The results showed that molybdenum ingested in liquid form was rapidly and totally absorbed into the circulation under ordinary intake regimes. The rates and extent of absorption were lower for composite meals, and also for increasing levels of administration. This information can be helpful in the application of the new ICRP model of the human alimentary tract.