Synthesis and in Vitro Characterization of Organometallic Rhenium and Technetium Glucose Complexes against Glut 1 and Hexokinase
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- 作者：Roger Schibli ; Cé ; cile Dumas ; Jeannine Petrig ; Loredana Spadola ; Leonardo Scapozza ; Elisa Garcia-Garayoa ; and P. August Schubiger
- 刊名：Bioconjugate Chemistry
- 出版年：2005
- 出版时间：January 2005
- 年：2005
- 卷：16
- 期：1
- 页码：105 - 112
- 全文大小：573K
- 年卷期：v.16,no.1(January 2005)
- ISSN：1520-4812
文摘
A series of nine organometallic technetium-99m and rhenium complexes of glucose are presented andcharacterized in vitro regarding their potential as surrogates of [18F]-2-fluoro-desoxy glucose ([18F]-FDG). The glucose derivatives are functionalized at positions C-1, C-2, C-3, and C-6. Different spacerlengths and chelating systems have been introduced at these sites. For the (radio)labeling, theorganometallic precursors [99mTc(H2O)3(CO)3]+ and [ReBr3(CO)3]2- respectively have been used. Theresulting complexes have been characterized chemically and radiochemically. The formation of uniformproducts has been observed on the macroscopic (Re) and no-carrier-added level (99mTc). The Tc-99mcomplexes revealed good inertness against ligand exchange (Cys and His) and excellent stability inphysiological buffered saline as well as in human plasma over a period of 24 h at 37 
C. The rheniumcomplexes have been tested for competitive inhibition of the (yeast) hexokinase. Only for C-2 derivatizedglucose complexes with extended spacer functionalities Ki values in the millimolar and sub-millimolarrange have been observed. In silico molecular docking experiments supported these experimentalfindings. However, the competitive inhibitors are not recognized as a pseudosubstrate of hexokinase.The cellular uptake of all 99mTc-complexes into HT-29 colon carcinoma cells via Glut1 was generallylow and unspecific independent of the position at the hexose ring, the chelating systems, or the overallcharge of the corresponding metal complexes. The current results seem to preclude the use of thesecompounds as [18F]-FDG surrogates primarily due to the low cellular uptake via Glut1.
C. The rheniumcomplexes have been tested for competitive inhibition of the (yeast) hexokinase. Only for C-2 derivatizedglucose complexes with extended spacer functionalities Ki values in the millimolar and sub-millimolarrange have been observed. In silico molecular docking experiments supported these experimentalfindings. However, the competitive inhibitors are not recognized as a pseudosubstrate of hexokinase.The cellular uptake of all 99mTc-complexes into HT-29 colon carcinoma cells via Glut1 was generallylow and unspecific independent of the position at the hexose ring, the chelating systems, or the overallcharge of the corresponding metal complexes. The current results seem to preclude the use of thesecompounds as [18F]-FDG surrogates primarily due to the low cellular uptake via Glut1.