| Tumour uptake of the radiolabelled somatostatin analogue [DOTA0, TYR3]octreotide is dependent on the peptide amount. | |
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MedLine Citation:
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PMID: 10398816 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Radiolabelled tumour receptor-binding peptides can be used for in vivo scintigraphic imaging. Recently, the somatostatin analogue [Tyr3]octreotide (D-Phe-c(Cys-Tyr-D-Trp-Lys-Thr-Cys)-Thr(ol)) was derivatized with the chelator DOTA (tetra-azacyclododecane-tetra-acetic acid), enabling stable radiolabelling with both the high-energy beta particle-emitter yttrium-90 and the Auger electron-emitter indium-111. The thus produced radiolabelled compounds are promising for peptide receptor radionuclide therapy. Our previous in vitro and in vivo (rat) experiments with these radiolabelled compounds showed favourable binding and biodistribution characteristics with high uptake and retention in the target organs. We also demonstrated receptor-specific, time- and temperature-dependent internalization of radiolabelled [DOTA0,Tyr3]octreotide in somatostatin receptor subtype 2 (sst2)-positive rat pancreatic tumour cell lines. In this study we have investigated the effects of differences in the amount of injected peptide on tissue distribution of 111In-labelled [DOTA0, Tyr3]octreotide in normal, i.e. non-tumour-bearing, and CA20948 tumour-bearing rats. This was done in order to find the amount of peptide at which the highest uptake in target tissues is achieved, and thereby to increase the potential of radionuclide therapy while simultaneously ensuring the lowest possible radiotoxicity in normal organs. Uptake of radiolabelled [DOTA0,Tyr3]octreotide in sst2-positive organs showed different bell-shaped functions of the amount of injected peptide, being highest at 0.05 (adrenals), 0.05-0. 1 (pituitary and stomach) and 0.25 (pancreas) microg. Uptake in the tumour was highest at 0.5 microg injected peptide. The highest uptake was found at peptide amounts that were lower than those reported for [111In-DTPA0]octreotide ((D-Phe-c(Cys-Phe-D-Trp-Lys-Thr-Cys)-Thr(ol), DTPA = diethylene-triamine-penta-acetic acid), consistent with the higher receptor affinity of the first compound. Our observations of mass-dependent differences in uptake of radiolabelled [DOTA0, Tyr3]octreotide, being the resultant of a positive effect of increasing amounts of peptide on, for example, receptor clustering and a negative effect of receptor saturation, are of consequence for rat radionuclide therapy studies with radiolabelled peptides and may also be of consequence for human radionuclide therapy studies with this compound. |
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Authors:
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M de Jong; W A Breeman; B F Bernard; A van Gameren; E de Bruin; W H Bakker; M E van der Pluijm; T J Visser; H R Mäcke; E P Krenning |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of nuclear medicine Volume: 26 ISSN: 0340-6997 ISO Abbreviation: Eur J Nucl Med Publication Date: 1999 Jul |
Date Detail:
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Created Date: 1999-09-16 Completed Date: 1999-09-16 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7606882 Medline TA: Eur J Nucl Med Country: GERMANY |
Other Details:
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Languages: eng Pagination: 693-8 Citation Subset: IM |
Affiliation:
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Department of Nuclear Medicine, University Hospital Dijkzigt, Rotterdam, The Netherlands. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Indium Radioisotopes / diagnostic use* Octreotide / analogs & derivatives*, diagnostic use, pharmacokinetics Pancreatic Neoplasms / radionuclide imaging* Radiopharmaceuticals / diagnostic use*, pharmacokinetics Rats Rats, Inbred Lew Tissue Distribution |
| Chemical | |
Reg. No./Substance:
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0/Indium Radioisotopes; 0/Radiopharmaceuticals; 0/octreotide, DOTA-Tyr(3)-; 83150-76-9/Octreotide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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