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Radiosynthesis and preclinical evaluation of [68Ga]Ga-NOTA-folate for PET imaging of folate receptor ?-positive macrophages.


ABSTRACT: Folate receptor ? (FR-?), a marker expressed on macrophages, is a promising target for imaging of inflammation. Here, we report the radiosynthesis and preclinical evaluation of [68Ga]Ga-NOTA-folate (68Ga-FOL). After determining the affinity of 68Ga-FOL using cells expressing FR-?, we studied atherosclerotic mice with 68Ga-FOL and 18F-FDG PET/CT. In addition, we studied tracer distribution and co-localization with macrophages in aorta cryosections using autoradiography, histology, and immunostaining. The specificity of 68Ga-FOL was assessed in a blocking study with folate glucosamine. As a final step, human radiation doses were extrapolated from rat PET data. We were able to produce 68Ga-FOL with high radiochemical purity and moderate molar activity. Cell binding studies revealed that 68Ga-FOL had 5.1 nM affinity for FR-?. Myocardial uptake of 68Ga-FOL was 20-fold lower than that of 18F-FDG. Autoradiography and immunohistochemistry of the aorta revealed that 68Ga-FOL radioactivity co-localized with Mac-3-positive macrophage-rich atherosclerotic plaques. The plaque-to-healthy vessel wall ratio of 68Ga-FOL was significantly higher than that of 18F-FDG. Blocking studies verified that 68Ga-FOL was specific for FR. Based on estimations from rat data, the human effective dose was 0.0105 mSv/MBq. Together, these findings show that 68Ga-FOL represents a promising new FR-?-targeted tracer for imaging macrophage-associated inflammation.

SUBMITTER: Moisio O 

PROVIDER: S-EPMC7423886 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Folate receptor β (FR-β), a marker expressed on macrophages, is a promising target for imaging of inflammation. Here, we report the radiosynthesis and preclinical evaluation of [<sup>68</sup>Ga]Ga-NOTA-folate (<sup>68</sup>Ga-FOL). After determining the affinity of <sup>68</sup>Ga-FOL using cells expressing FR-β, we studied atherosclerotic mice with <sup>68</sup>Ga-FOL and <sup>18</sup>F-FDG PET/CT. In addition, we studied tracer distribution and co-localization with macrophages in aorta cryosec  ...[more]

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