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.