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The in vivo disposition and in vitro transmembrane transport of two model radiometabolites of DOTA‐conjugated receptor‐specific peptides labelled with 177 Lu
Author(s) -
Volková Marie,
Mandíková Jana,
Bárta Pavel,
Navrátilová Lucie,
Lázníčková Alice,
Trejtnar František
Publication year - 2015
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3352
Subject(s) - chemistry , in vivo , pharmacokinetics , metabolite , dota , in vitro , renal physiology , pharmacology , stereochemistry , biochemistry , chelation , organic chemistry , renal function , biology , medicine , microbiology and biotechnology
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, 177 Lu‐DOTA‐ D Phe, and a tripeptide metabolite of 177 Lu‐DOTA‐minigastrin 11, 177 Lu‐DOTA‐ D Glu‐Ala‐Tyr. Their pharmacokinetics was compared with that of respective parent 177 Lu‐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 177 Lu‐DOTA‐ D Phe was lower than that of 177 Lu‐DOTA‐ D Glu‐Ala‐Tyr. An uptake of 177 Lu‐DOTA‐ D Phe 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.