The involvement of selected membrane transport mechanisms in the cellular uptake of (177)Lu-labeled bombesin, somatostatin and gastrin analogues
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25288534
DOI
10.1016/j.nucmedbio.2014.09.003
PII: S0969-8051(14)00507-1
Knihovny.cz E-resources
- Keywords
- Fluid phase endocytosis, Megalin, Nephrotoxicity, Organic anion transporter, Organic cation transporter, Peptides,
- MeSH
- Biological Transport MeSH
- Bombesin chemistry metabolism MeSH
- Cell Membrane metabolism MeSH
- Endocytosis * MeSH
- Gastrins chemistry metabolism MeSH
- HeLa Cells MeSH
- Isotope Labeling MeSH
- Humans MeSH
- Lutetium * MeSH
- Peptide Hormones chemistry metabolism MeSH
- Swine MeSH
- Organic Anion Transporters, Sodium-Independent metabolism MeSH
- Organic Anion Transport Protein 1 metabolism MeSH
- Somatostatin chemistry metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Bombesin MeSH
- Gastrins MeSH
- Lutetium * MeSH
- Peptide Hormones MeSH
- Organic Anion Transporters, Sodium-Independent MeSH
- Organic Anion Transport Protein 1 MeSH
- SLC22A7 protein, human MeSH Browser
- Somatostatin MeSH
INTRODUCTION: Radiolabeled receptor-targeting peptides are a useful tool for the diagnostic imaging and radiotherapy of some malignancies. However, the retention of radioactivity in the kidney may result in renal radiotoxic injury. This study seeks to evaluate the role of endocytic receptor megalin, renal SLC influx transporters and fluid phase endocytosis (FPE) in the cellular accumulation of radiolabeled peptides. METHODS: In vitro transport cellular studies using megalin ligands (RAP, albumin), fluid phase endocytosis (FPE) inhibitor rottlerin and low temperature were employed to evaluate the transport mechanisms of the peptides. Cells transfected with hOAT1 or hOCT2 were used to analyze the role of these SLC transporters. Somatostatin ((177)Lu-DOTA-[Tyr(3)]octreotate, (177)Lu-DOTA-[1-Nal(3)]octreotide), gastrin ((177)Lu-DOTA-sargastrin) and bombesin ((177)Lu-DOTA-[Pro(1),Tyr(4)]bombesin, (177)Lu-DOTA-[Lys(3)]bombesin, (177)Lu-PCTA-[Lys(3)]bombesin) analogues were involved in the study. RESULTS: RAP, albumin and low temperature decreased the accumulation of all the studied peptides significantly. With one exception, rottlerin caused the concentration dependent inhibition of the cellular accumulation of the radiopeptides. No significant differences in the uptake of the peptides between the control cells and those transfected with hOAT1 or hOCT2 were observed. CONCLUSION: The study showed that active transport mechanisms are decisive for the cellular accumulation in all tested (177)Lu-labeled somatostatin, gastrin and bombesin analogues. Besides receptor-mediated endocytosis by megalin, FPE participates significantly in the uptake. The tested types of renal SLC transporters are not involved in this process.
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