Design of silicon-based misonidazole analogues and (18)F-radiolabelling.
BACKGROUND
Development of new (18)F-labeled tracers for positron emission tomography (PET) imaging is increasingly important. Herein, we described the synthesis of silicon analogues of [(18)F]fluoromisonidazole in order to develop new radiolabelled compounds for the detection of tumour hypoxic domain. Their stabilities and their in vivo biodistribution were evaluated.


METHODS
(18)F-labeled silicon-based misonidazole analogues were synthesized by alkylating 2-nitroimidazole with alkyloxy-(3-chloropropyl)dialkyl or diarylsilane. These intermediates were labeled with [(18)F]F(-) with a mixture of K(18)F and Kryptofix (K222) in acetonitrile as standard condition. PET imaging was performed using a dedicated small animal PET scanner.


RESULTS
(18)F-labeled silicon-based misonidazole analogues were easily synthesized in three steps. The hydrolytic and radiolytic stability of these new fluorosilanes depend on the steric hindrance at the silicon center. Indeed, partial uptake of dimethylfluorosilane [(18)F]2a(1-(3-(Fluorodimethylsilyl)propyl)-2-nitro-1H-imidazole) in tumor hypoxic area was observed but defluorination also appeared. Moreover, PET studies indicated that, owing to its high lipophilicity, the most stable dinaphtylfluorosilane [(18)F]2d is retained mainly by the lungs.


CONCLUSIONS
We have described an efficient and versatile approach for the synthesis of (18)F-labeled, silicon-based misonidazole analogues. PET imaging of one of these compounds revealed that hypoxia could be detected. Controlling the biodistribution of (18)F-labeled silicon-based misonidazole analogues will require additional studies.
Bohn
Pierre
P
Department of Nuclear Medicine, Henri Becquerel Center and Rouen University Hospital and QuantIF- LITIS (EA4108), Rouen Cedex, France.
Deyine
Abdallah
A
Azzouz
Rabah
R
Bailly
Laetitia
L
Fiol-Petit
Catherine
C
Bischoff
Laurent
L
Fruit
Corinne
C
Marsais
Francis
F
Vera
Pierre
P
D000818:Animals; D045744:Cell Line, Tumor; D005354:Fibrosarcoma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008809:Mice, Inbred C3H; D008920:Misonidazole / Q000737:chemistry* / Q000493:pharmacokinetics*; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D012825:Silicon / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D008920:Misonidazole; D012825:Silicon