The in vivo disposition and in vitro transmembrane transport of two model radiometabolites of DOTA‐conjugated receptor‐specific peptides labelled with 177Lu

In vivo metabolism of the radiolabelled receptor‐specific peptides has been described; however, information regarding the pharmacokinetic behaviour of the degradation products within the body is very scarce. The present study was designed to obtain new knowledge on the disposition and elimination of low‐molecular radiometabolites of receptor‐specific peptides in the organism and to reveal the potential involvement of selected membrane transport mechanisms in the cellular uptake of radiometabolites, especially in the kidney. The study compared pharmacokinetics of two radiometabolites: a final metabolite of somatostatin analogues, ¹⁷⁷Lu‐DOTA‐DPhe, and a tripeptide metabolite of ¹⁷⁷Lu‐DOTA‐minigastrin 11, ¹⁷⁷Lu‐DOTA‐DGlu‐Ala‐Tyr. Their pharmacokinetics was compared with that of respective parent ¹⁷⁷Lu‐radiopeptide. Both radiometabolites exhibited relative rapid clearing from most body tissues in rats in vivo along with predominant renal excretion. The long‐term renal retention of the smaller radiometabolite ¹⁷⁷Lu‐DOTA‐DPhe was lower than that of ¹⁷⁷Lu‐DOTA‐DGlu‐Ala‐Tyr. An uptake of ¹⁷⁷Lu‐DOTA‐DPhe by human renal influx transporter organic cation transporter 2 was found in vitro in a cellular model. The study brings the first experimental data on the in vivo pharmacokinetics of radiometabolites of receptor‐specific somatostatin and gastrin analogues. The found results may indicate a negative correlation between the degree of decomposition of the parent peptide chain and the renal retention of the metabolite.