18F-Trifluoroborate Derivatives of [Des-Arg10]Kallidin for Imaging Bradykinin B1 Receptor Expression with Positron Emission Tomography

摘要: Bradykinin B1 receptor (B1R) is involved in pain and inflammation pathways upregulated inflamed tissues cancer. Due to its minimal expression healthy tissues, B1R an attractive target for the development of therapeutic agents treat inflammation, chronic pain, The goal this study synthesize compare two (18)F-labeled peptides derived from potent antagonists B9858 B9958 imaging with positron emission tomography (PET). Azidoacetyl-B9858 2 azidoacetyl-B9958 3 were synthesized by a solid-phase approach subsequently clicked ammoniomethyl-trifluoroborate (AmBF3)-conjugated alkyne 1 obtain AmBF3-B9858 AmBF3-B9958, respectively. AmBF3-B9958 bound high affinity, Ki values at 0.09 ± 0.08 0.46 0.03 nM, respectively, as measured vitro competition binding assays. (18)F labeling was performed via (18)F-(19)F isotope exchange reaction. radiofluorinated tracers obtained within synthesis time 30 min 23-32% non-decay-corrected radiochemical yield, >99% purity, 43-87 GBq/μmol specific activity end synthesis. PET biodistribution studies carried out mice bearing both B1R-positive (B1R(+)) HEK293T::hB1R B1R-negative (B1R(-)) HEK293T tumors. Both cleared rapidly most organs/tissues, mainly through renal pathway. High uptake B1R(+) tumors ((18)F-AmBF3-B9858: 3.94 1.24% ID/g, tumor-to-muscle ratio 21.3 4.33; (18)F-AmBF3-B9958: 4.20 0.98% 48.6 10.7) observed h postinjection. These results indicate that (18)F-AmBF3-B9858 (18)F-AmBF3-B9958 are promising vivo PET.