Biodistribution study of lutetium hydroxyapatite (177Lu-HA) for liver cancer therapy

Abstract

This study aimed to determine the organ at risk (OAR) of 177Lu-HA in liver cancer therapy using the biodistribution study and model selections method. Administration of 177Lu-HA was carried out directly on the intra-artery of Wistar rat liver by surgery. Pharmacokinetics data of 177Lu-HA in Wistar rats from different organs, such as liver, kidneys, and spleen, were obtained from the literature. Thirteen sums of exponentials (SOE) functions and one logistic function were used and fitted to the pharmacokinetics data in different organs. The goodness of fit was tested based on the visualization of the fitted graphs, coefficient of variations of the fitted parameters (CV<50%), and the elements of the correlation matrix (0,8≤CM≤0,8). The best function was selected based on the corrected Akaike information criterion (AICc) and was used for the subsequent calculation of time-integrated activity coefficients (TIACs). Human TIACs were predicted by extrapolating rat TIACs using the time-scaling method, as suggested in the literature. In this study, an organ with the highest TIACs/organ mass values in humans was identified as the OAR. In general, mathematical functions were successfully fitted to the pharmacokinetic data of 177Lu-HA in all organs with a good fit based on the goodness of fit criteria. The best functions were f2b(t)=A1e−(λ1+λp)t+(100−A1)e−λpt, f3a(t)=A1e−(λ1+λp)t+A2e−λpt, Lf1(t)=A1+Ce−Bt' and f4c(t)=−A1e−(λ1+λp)t+A2e−(λ2+λp)t+(100−A1−A2) for blood/kidney/GI, stomach, skeleton/spleen and liver, respectively. The calculated human TIACs/organ mass (hour/gram) were 2.78E+0, 5.59E-4, 4.57E-3, 1.56E-2, 1.15E-3, 7.40E-2, 5.55E-2 for liver, blood, kidneys, GI, stomach, skeleton, and spleen, respectively. Based on these calculations, it can be concluded that the OAR of 177Lu-HA that was administrated directly into the intra-arterial liver of the Wistar rat are liver, skeleton, and spleen.