The biological properties of receptor-targeted peptides have made them popular diagnostic imaging and therapeutic agents. Typically, the synthesis of fluorine-18 radiolabeled receptor-targeted peptides for positron emission tomography (PET) imaging is a time consuming, complex, multi-step synthetic process that is highly variable based on the peptide. The complexity associated with the radiolabeling route and lack of robust automated protocols can hinder translation into the clinic. A fully automated batch production to radiolabel three peptides (YGGFL, cRGDyK, and Pyr-QKLGNQWAVGHLM) from fluorine-18 using the ELIXYS FLEX/CHEM® radiosynthesizer in a two-step process is described. First, the prosthetic group, 6-[ 18 F]fluoronicotinyl-2,3,5,6-tetrafluorophenyl ester ([ 18 F]FPy-TFP) was synthesized and subsequently attached to the peptide. The [ 18 F]FPy-peptides were synthesized in 13-26% decay corrected yields from fluorine-18 with high molar activity 1-5 Ci mmol À1 and radiochemical purity of >99% in an overall synthesis time of 97 AE 3 minutes.
We previously reported the identification and structure-activity analysis of bithiazole-based correctors of defective cellular processing of the cystic fibrosis-causing CFTR mutant, ΔF508-CFTR. Here, we report the synthesis and uptake of a functional, fluorescently labeled bithiazole corrector. Following synthesis and functional analysis of four bithiazole-fluorophore conjugates, we found that 5, a bithazole-based BODIPY conjugate, had low micromolar potency for correction of defective δF508-CFTR cellular misprocessing, with comparable efficacy to benchmark corrector corr-4a. Intravenous administration of 5 to mice established its stability in extrahepatic tissues for tens of minutes. By fluorescence imaging of whole-body frozen slices, fluorescent corrector 5 was visualized strongly in gastrointestinal organs, with less in lung and liver. Our results provide proof-of-concept for mapping the biodistribution of a ΔF508-CFTR corrector by fluorophore labeling and fluorescence imaging of whole-body slices.
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