Bias and precision analysis in curve fitting for hyperthyroidism clinical dosimetry

Optimizing uptake assessment schedules is critical for minimizing uncertainties in internal dosimetry. We performed a simulation study based on patient-specific biokinetics from iodine-131 (¹³¹I)-sodium iodide (NaI) hyperthyroidism treatments to evaluate the impact of measurement precision and sampling timing on the bias and precision of the time-integrated activity (TIA) estimates.

Patient biokinetics were simulated using a two-compartment model, with parameters derived from the distribution of a cohort undergoing planning dosimetry. Uptake measurements were then simulated with variable relative noise for each simulated patient. The bias and precision were calculated as the mean and standard deviation, respectively, of the difference between the fitted and true TIA values.

Graphs illustrate the estimated TIA bias and precision as functions of measurement precision for various uptake assessment schedules; values for 5% and 10% measurement precision are provided in tables.

For the uptake assessment schedules considered, the TIA bias is negative and for schemes with more than one uptake measurements it depends on measurement precision with increasing magnitude. The precision and bias for the (5, 24, 168)h and (24, 168)h post-administration uptake assessment schemes are comparable. The last uptake assessment should not be performed earlier than 6 days post-administration to keep the TIA precision below 15% for a 10% measurement precision. The use of error propagation and the Hessian matrix for curve fit parameter uncertainty estimation leads to an overestimation of the true curve integral uncertainty for large uptake assessment uncertainties.