C-glyco“RGD” as αIIbβ3 and αvβ integrin ligands for imaging applications: Synthesis, in vitro evaluation and molecular modeling

Fully automated radiosynthesis of [18F]fluoro-C-glyco-c(RGDfC): exploiting all the abilities of the AllInOne synthesizer

“…C-glycosidic compounds, thanks to their robust C-C link at pseudo-anomeric position, are resistant to acidic and enzymatic hydrolysis and are thus stable in vivo. 9,44,45 A C-glucoside derivative in beta configuration was designed with a spacer-arm bearing an azido group, necessary for the CuAAC. A three carbons spacer-arm has shown a good flexibility and steric arrangement in the final C-glyco-c(RGDfC), conferring an affinity in the same range than native c(RGDfC) toward  v  3 integrin.…”

“…A three carbons spacer-arm has shown a good flexibility and steric arrangement in the final C-glyco-c(RGDfC), conferring an affinity in the same range than native c(RGDfC) toward  v  3 integrin. 9 This is of particular importance, because the introduction of prosthetic group on biomolecules can sometimes generate an affinity decrease.…”

“…Radiolabeling precursor 2 was easily obtained from 1 by reacting triflic anhydride with pyridine as base in 80% yield (Scheme 1). 9 Triflate was chosen as leaving group for its high reactivity. Triflated compounds could be less stable compared to tosylated compounds for example, but 2 was stable several weeks and even months at -20°C.…”

“…The first step was the 18 Fradiolabeling of precursor 2 in the reactor 1. By taking advantage of our previous work on glycoside based prosthetic groups, 9,10 in order to obtain a high radiolabeling rate and a better repeatability, different parameters such as the amount of precursor, the reaction duration and the temperature were screened upstream. The following conditions were found to be optimal for the 18 F-radiofluorination: 5 mg of precursor in 2 mL of dry acetonitrile and reaction of 5 min at 95°C.…”

“…[6][7][8] For example, cyclic arginine-glycine-aspartic acid(RGD)-containing peptides have been the focus of intense investigations toward the development of PET radiotracers in cancer diagnosis because they bind with high specificity and affinity to α v β 3 integrin. [9][10][11][12][13][14][15] Several labeled cyclic RGD peptides have been investigated and some of them are nowadays employed in clinical use for PET imaging of angiogenesis in cancer. 11,12,[15][16][17][18] Fluorine-18 ( 18 F) is a commonly used radioelement for peptide radiolabeling because of its ease of production, low positron energy, high specific activity and appropriate half-life (t 1/2 = 109.8 min) compatible with multistep synthesis.…”