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The biodistribution of NC100668 and the effect of excess NC100668 on the biodistribution and kidney retention of Tc-99m-NC100668 in the rat
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- Edwards, David (author)
- Uppsala universitet,Enheten för radiologi,Ahlström
- Lewis, Joanne (author)
- Battle, Mark (author)
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- Lear, Rochelle (author)
- Farrar, Gill (author)
- Barnett, D. Jon (author)
- Godden, Vanessa (author)
- Edwards, Catherine (author)
- Oliveira, Alexandra (author)
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- (creator_code:org_t)
- Elsevier BV, 2007
- 2007
- English.
- In: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 34:3, s. 315-323
- Journal article (peer-reviewed)
Abstract
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- INTRODUCTION: (99m)Tc-NC100668 is being developed to aid the diagnosis of thromboemboli. The purpose of this study was to investigate if the presence of excess NC100668 interferes with the biodistribution and blood clot uptake of (99m)Tc-NC100668. The secondary aim was to investigate the causes underlying the kidney retention of (99m)Tc-NC100668. METHODS: The uptake of a (14)C-labelled analogue of NC100668, as well as (99m)Tc-NC100668, into plasma (in vitro) and blood (in vivo) clots was determined. The biodistribution of (99m)Tc-NC100668 at a range of NC100668 doses was studied in normal Wistar rats and those bearing experimentally induced deep venous thrombosis. The biodistribution of a negative control peptide and (99m)Tc-NC100668 plus L-lysine was studied in healthy male Wistar rats. RESULTS: The biodistribution as well as plasma clot uptake of [Asn-U-(14)C]NC100668 and (99m)Tc-NC100668 was similar. Apart from some reduction in kidney retention, the biodistribution and uptake of radioactivity into the blood clot were not significantly affected by the presence of up to 1000 times the clinical dose of NC100668. Kidney retention of radioactivity could be more effectively reduced by coadministration of 889 microg/kg NC100668 than 450 mg/kg L-lysine. A negative control peptide with no affinity for FXIIIa demonstrated very little kidney retention. CONCLUSIONS: The biodistribution and blood clot uptake of (99m)Tc-NC100668 and [Asn-U-(14)C]NC100668 are similar. With the exception of the kidneys, (99m)Tc-NC100668 biodistribution and blood clot uptake are unaffected by the presence of unlabelled NC100668. The kidney retention of radioactivity is probably due to transglutaminase activity and, to a lesser extent, nonspecific charge-mediated endocytosis.
Keyword
- 99mTc-NC100668
- Biodistribution
- Ligand dose
- Thrombus
- Rat
- MEDICINE
- MEDICIN
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- ref (subject category)
- art (subject category)
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- Edwards, David
- Lewis, Joanne
- Battle, Mark
- Lear, Rochelle
- Farrar, Gill
- Barnett, D. Jon
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- Edwards, Catheri ...
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- Ahlström, Håkan
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