Radiosynthesis and Bioevaluation of (99m)Tc-Labeled Isocyanide Ubiquicidin 29-41 Derivatives as Potential Agents for Bacterial Infection Imaging

放射合成和生物活性评价(99m)Tc标记的异氰化物泛素29-41衍生物作为细菌感染成像的潜在试剂

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Abstract

To develop a novel (99m)Tc-labeled ubiquicidin 29-41 derivative for bacterial infection single-photon emission computed tomography (SPECT) imaging with improved target-to-nontarget ratio and lower nontarget organ uptake, a series of isocyanide ubiquicidin 29-41 derivatives (CNnUBI 29-41, n = 5-9) with different carbon linkers were designed, synthesized and radiolabeled with the [(99m)Tc]Tc(I)(+) core, [(99m)Tc][Tc(I)(CO)(3)(H(2)O)(3)](+) core and [(99m)Tc][Tc(V)N](2+) core. All the complexes are hydrophilic, maintain good stability and specifically bind Staphylococcus aureus in vitro. The biodistribution in mice with bacterial infection and sterile inflammation demonstrated that [(99m)Tc]Tc-CN5UBI 29-41 was able to distinguish bacterial infection from sterile inflammation, which had an improved abscess uptake and a greater target-to-nontarget ratio. SPECT imaging study of [(99m)Tc]Tc-CN5UBI 29-41 in bacterial infection mice showed that there was a clear accumulation in the infection site, suggesting that this radiotracer could be a potential radiotracer for bacterial infection imaging.

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