Abstract
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Objectives The recent development of positron emission tomography imaging has been correlated with a crucial need for new techniques to introduce radionuclides onto biologically active molecules. However, the introduction of fluorine atom may be difficult on many molecules but we describe herein a methodology using silicon as fluorine acceptor. We wish to report the design, the synthesis and preliminary biological results of these new hypoxia tracers based on a nitroimidazole group.
Methods The synthesis and fluorination of various silyl ethers used as precursor were conducted by means of SN2 reaction. The design of molecular library is based on various parameters such as nitroimidazole group to reach hypoxic tissues, silicon atom as fluoride acceptor and a linker. Fig. 1.
Results To a solution of silamisonidazole in acetonitrile (0.1 mL, 0.15M) was added 18F-fluoride potassium (150 mCi) and glacial acetic acid (0.05 mL). This mixture was stirred at 75°C for 20 min. The crude product was submitted to an HPLC purification (H2O/ACN : 20/80).R1 = R2 = Me: Yield: >90%, T(1/2) = <5 min.R1 = R2 = iPr: Yield: >70%, T(1/2) = 7 min.R1 = R2 = Np: Yield: >60%, T(1/2) = 130 min.
Conclusions A series of new hypoxia tracers, structurally related to misonidazole, exhibited an easier fluoro-labeling. Stability of these compounds increased if R2 and R3 were bulky, and correlated with the steric hindrance.
- © 2009 by Society of Nuclear Medicine