Tumour-to-Kidney Absorbed Dose Ratios for Alpha-Emitter PRRTs Estimated with [¹⁷⁷Lu]Lu-DOTATATE SPECT Images and Biokinetic Models: Patient Variations Impact Contribution from Redistributing Daughters.

Abstract

Biokinetics for potential alpha-emitter peptide receptor radionuclide therapies (PRRTs) were simulated to estimate tumour-to-kidney absorbed dose ratios for ²²⁵Ac, ²²⁷Th, ²¹²Pb, ²³⁰U, ²²⁶Ac, ²¹¹At, and ¹⁴⁹Tb. The impact of daughter redistribution was studied, along with the effects of differing biokinetics and modelling assumptions. Post-injection whole body probe measurements and SPECT/CT images at five and four time points, respectively, of 14 patients receiving [¹⁷⁷Lu]Lu-DOTATATE were used to estimate whole body, tumour, and kidney time-activity curves. Alpha-emitter PRRT biokinetics were estimated by adjusting time-activity curves by the physical half-lives of parent radionuclides. Daughter redistribution was included, assuming all alpha decays and separate scenarios with 0%, 16%, 36%, and 100% of beta decays released daughters to ICRP biokinetic models. The initial conditions of the biokinetic models were changed to assess the impact of modelling assumptions. The tumour-to-kidney absorbed dose ratios were compared. Variations between patients was assessed by coefficient of variation (CoV). Inter-patient variation in whole body time-integrated activities increased with physical half-life of the parent radionuclide. For ²¹²Pb, ²²⁵Ac, and ²²⁷Th there was large inter-patient variation in kidney absorbed dose change when incorporating daughter redistribution (absolute CoV >40%), while for ²²⁶Ac and ²³⁰U it was consistent between patients (absolute CoV <3%). Modifying the distribution in the biokinetic models impacted the kidney absorbed dose, but different modifications impacted different decay chains. Tumour-to-kidney absorbed dose ratios tended to increase with parent half-life, but for some decay chains the effect of rate of daughter release from tumours was notable. The trend for tumour-to-kidney absorbed dose ratios should be weighed against other important aspects for radionuclide therapies, and considered with the uncertainty in the underlying assumption of equivalent biokinetics. The large inter-patient variations resulting from daughter redistribution for ²¹²Pb, ²²⁵Ac, and ²²⁷Th kidney absorbed doses underline the need for representative patient cohorts.