The in vivo disposition and in vitro transmembrane transport of two model radiometabolites of DOTA-conjugated receptor-specific peptides labelled with (177) Lu
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26526343
DOI
10.1002/jlcr.3352
Knihovny.cz E-resources
- Keywords
- minigastrins, nephrotoxicity, organic anion transporter, organic cation transporter, pharmacokinetics, somatostatin analogues,
- MeSH
- Madin Darby Canine Kidney Cells MeSH
- Phenylalanine analogs & derivatives chemistry pharmacokinetics MeSH
- Gastrins chemistry pharmacokinetics MeSH
- HeLa Cells MeSH
- Coordination Complexes chemistry pharmacokinetics MeSH
- Rats MeSH
- Kidney metabolism MeSH
- Humans MeSH
- Oligopeptides chemistry pharmacokinetics MeSH
- Rats, Wistar MeSH
- Organic Cation Transport Proteins metabolism MeSH
- Dogs MeSH
- Radiopharmaceuticals chemistry pharmacokinetics MeSH
- Somatostatin analogs & derivatives chemistry MeSH
- Tissue Distribution MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Dogs MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 177Lu-DOTA-Glu-Ala-Tyr MeSH Browser
- 177Lu-DOTA-minigastrin 11 MeSH Browser
- 177Lu-DOTA-Phe MeSH Browser
- Phenylalanine MeSH
- Gastrins MeSH
- Coordination Complexes MeSH
- minigastrin MeSH Browser
- Oligopeptides MeSH
- Organic Cation Transport Proteins MeSH
- Radiopharmaceuticals MeSH
- Somatostatin MeSH
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-DPhe, and a tripeptide metabolite of (177)Lu-DOTA-minigastrin 11, (177)Lu-DOTA-DGlu-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-DPhe was lower than that of (177)Lu-DOTA-DGlu-Ala-Tyr. An uptake of (177)Lu-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.
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