Synthesis And Evaluation Of Al¹⁸F-NODA Complex Conjugated Benzothiazole Analog As Potential Imaging Agents

OBJECTIVES To develop Al¹⁸F-radiolabled tracers,derivated from2-phenylbenzothiazole analogs,as PET probes for tumor or cerebral amyloid angiopathy?CAA?imaging.METHODS Probes for tumor imaging(Al¹⁸F-1.5)and CAA imaging(Al¹⁸F-2.9,Al¹⁸F-2.10)were prepared through a“one-pot,two-step”radiolabelling process and evaluated in vitro by competition studies.Uptake study and fluorescent staining were displayed to Al¹⁸F-1.5 in addition.Furthermore,biodistribution studies was performed with these three probes and PET imaging was implied extra for Al¹⁸F-1.5.RESULTS Al¹⁸F-1.5 exhibited high uptake in HeLa cells?24.7±0.9%ID/10⁶ cells?and MCF-7 cells?6.8±0.3%ID/10⁶ cells?in uptake experiments.In competition assay,Al¹⁸F-1.5 displayed specificity for HeLa cells and MCF-7 cells(IC₅₀=63.8±13.6 nM and 331.1±33.7 nM,respectively).The nonradioactive compound,Al¹⁹F-1.5,visibly marked HeLa cells and MCF-7 cells but did not stain HEB cells in florescent staining.In in vivo PET imaging,HeLa and MCF-7 tumors were clearly delineated by specific accumulation of Al¹⁸F-1.5.Biodistribution study in mice bearing HeLa and MCF-7 xenografts revealed that Al¹⁸F-1.5 exhibited good tumor uptake?4.66±0.13%ID/g and 3.69±0.56%ID/g,respectively?,good tumor-to-muscle ratio?3.38 and 2.48,respectively?at 1h post injection.For CAA imaging agents,competition assay showed Al¹⁹F-2.9?K_i=75.3±31.5 nM?and Al¹⁹F-2.10?K_i=82.4±19.8 nM?have moderate affinities to A?_1-42 in vitro.Lower uptake and faster clearance were displayed from the result of biodistribution in vivo as well.CONCLUSIONS We successfully synthesized three PET agents called Al¹⁸F-1.5 for tumor imaging and Al¹⁸F-2.9/2.10 for CAA imaging.Al¹⁸F-1.5 showed great stability and activity to tumors,Al¹⁸F-2.9 and Al¹⁸F-2.10 improved characters in vivo with introducing PEG linker,which indicated they are all the potential candidates to be developed as positron imaging agents.