A new 18F-labelled derivative of the MMP inhibitor CGS 27023A for PET: radiosynthesis and initial small-animal PET studies.
The CGS 27023A derivative (R)-2-(N-((6-fluoropyridin-3-yl)methyl)-4-methoxyphenyl-sulphonamido)-N-hydroxy-3-methylbutanamide 1a was identified as a very potent matrix metalloproteinase inhibitor. Here, we describe a one-step radiosynthesis of the target compound [(18)F]1a. The syntheses of [(18)F]1a resulted in a radiochemical yield of 12.1+/-5.9% (decay-corrected), a radiochemical purity of 98.8+/-0.6%, and a specific activity of 39+/-27 GBq/micromol at the end of synthesis within 160+/-18 min from the end of radionuclide production (n=5). Initial small-animal PET studies in wild-type mice (C57/BL6) showed no unfavourable tissue accumulation of [(18)F]1a.
Wagner
Stefan
S
Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Str. 33, D-48149 Münster, Germany. stwagner@uni-muenster.de
Breyholz
Hans-Jörg
HJ
Höltke
Carsten
C
Faust
Andreas
A
Schober
Otmar
O
Schäfers
Michael
M
Kopka
Klaus
K
D000818:Animals; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006877:Hydroxamic Acids / Q000138:chemical synthesis*; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D049268:Positron-Emission Tomography; D011480:Protease Inhibitors / Q000138:chemical synthesis*; D011719:Pyrazines / Q000138:chemical synthesis*; D013449:Sulfonamides / Q000138:chemical synthesis
C097658:CGS 27023A; D005462:Fluorine Radioisotopes; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D011719:Pyrazines; D013449:Sulfonamides