A five‐compartment biokinetic model for ⁹⁰Y‐DOTATOC therapy

Abstract

Purpose Neuroendocrine tumors (NETs) are now routinely treated by radiopeptide targeted therapy using somatostatin receptor‐binding peptides such as 90Y‐ and 177Lu‐DOTATOC. The objective of this work was to develop a biokinetics model of 90Y labelled DOTATOC, which is applied in the therapy of NETs to estimate doses in kidney and tumor. Methods A multi‐compartment model described by two sets of differential equations, one set for the actual 30‐min infusion and the other set for the post‐infusion period was developed and activities were measured by liquid scintillation counting in blood (compartment 1) and the urine (compartment 3). The inter‐compartment transfer coefficients, λij, were varied to yield the best fit of the calculated to the measured time‐activity data and the 90Y‐DOTATOC time‐activity data in the five‐compartments comprising the human body were thus determined. The resulting time‐activity curves were integrated over the interval from 0 to 72 h post administration to obtain the number of radioactive decays in each compartment and, in case of the kidneys and tumor, then multiplied by the self‐dose 90Y beta particle absorbed fraction, determined by Monte Carlo (MC) simulation, the kidney and tumor absorbed doses. Results Transfer coefficients λij, were determined for five‐compartments for all patients. Time‐ activity curves of 90Y‐DOTATOC in 14 patients were determined, and two typical ones are shown graphically. Absorbed doses in the tumor and kidneys, obtained by the developed method, were determined. The mean absorbed dose in a kidney per unit of administered activity is 1.43 mGy/MBq (range 0.73–2.42 mGy/MBq). The tumor dose was determined as 30.94 mGy/MBq (range 20.05–42.31 mGy/MBq). Conclusion Analytical solution of a biokinetic model for 90Y‐DOTATOC therapy enabled determination of the transfer coefficients and derivation of time‐activity curves and kidney and tumor absorbed doses for 14 treated patients. The model can be applied to other radionuclides where elimination is predominantly through urine, which is often the case in radiopharmaceuticals.

Classification of tolerable/intolerable mucosal toxicity of head‐and‐neck radiotherapy schedules with a biomathematical model of cell dynamics

“…Systems of differential equations have previously been used to model dynamics of cell populations in normal tissues, including, for example, toxicity 14 and cancer induction, 15 tumor reoxygenation, 16 or response to molecular radiotherapy. 17 , 18 We validate our model in an extended dataset of tolerability/intolerability of head‐and‐neck schedules, building upon those provided in Refs. [ 7 , 8 ], and adding some additional schedules.…”