Inflammation plays a significant role in many physiological and pathological processes. Molecular imaging could provide functional as well as anatomical information for visualizing various inflammatory diseases. Advancements in imaging tracers for inflammation would improve the accuracy of diagnosis and monitoring, thus facilitating patient care. The positron emission tomography (PET) imaging tracer, 68 Ga-labeled antagonist peptide Trp-Arg-Trp-Trp-Trp-Trp (WRWWWW, WRW 4 ), targets formyl peptide receptor 2 (FPR2), which is in turn widely distributed in a variety of tissues and is associated with many inflammatory diseases. In the current study, we aimed to investigate the potential of 68 Ga-WRW 4 for detecting and monitoring inflammatory lesions in mice. We established an inflammation mouse model by the intramuscular injection of turpentine oil into the left thigh. WRW 4 was labeled with 68 Ga with an overall radiochemical yield >90% and radiochemical purity >99%. 68 Ga-WRW 4 uptake in inflamed muscle peaked on day 2 (1.14 ± 0.01 percentage of the injected dose per gram of tissue (%ID/g)) and the uptake ratio of inflammatory/normal muscle also reached a maximum (12.36 ± 2.35). Strong PET signals were detected in the left thigh at 60 min after the injection of 68 Ga-WRW 4 in experimental mice, but weak or no signals were detected in mice in the blocking and control groups. 68 Ga-WRW 4 uptake was in agreement with the dynamics of immune cell infiltration during the inflammatory reaction. These results suggest that 68 Ga-WRW 4 is a promising PET tracer suitable for the noninvasive detection of FPR2 expression and for monitoring inflammatory activity in inflammation-bearing mice.
Positron emission tomography (PET)/near-infrared fluorescence (NIRF) dual-modal imaging presents an enticing prospect for tumor diagnosis and surgical navigation. In this study, we developed a novel probe IR808-DOTA for tumor-targeted PET/NIRF imaging, image-guided surgery, and photothermal therapy. This construct had better water solubility and pharmacokinetics than IR808 and had similar photophysical properties, tumor targeting ability, and photothermal anticancer effect to IR808. By a simple labeling process, IR808-DOTA was labeled with gallium-68 and applied as a PET probe for tumor imaging in MCF-7 tumor xenografted mice. IR808-DOTA itself acted as an NIRF imaging agent in the following surgery for intraoperative navigation to aid surgeons in the delineation of tumor margins and visualizing sentinel lymph nodes to facilitate a more thorough tumor resection. Irradiation by laser, IR808-DOTA could prominently inhibit tumor growth in MCF-7 subcutaneous tumor model mice by directly ablating tumor cells, inhibiting tumor proliferation, and promoting tumor cell apoptosis. In summary, 68Ga-DOTA-IR808 could enable a convenient and user-friendly workflow for tumor imaging and guided surgery, and therefore, it may have great prospects for clinical translation as a PET/NIRF dual-modal probe.
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