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- Title
Radiosynthesis and preclinical evaluation of [68Ga]Ga-NOTA-folate for PET imaging of folate receptor β-positive macrophages.
- Authors
Moisio, Olli; Palani, Senthil; Virta, Jenni; Elo, Petri; Liljenbäck, Heidi; Tolvanen, Tuula; Käkelä, Meeri; Miner, Maxwell G.; Herre, Erika Atencio; Marjamäki, Päivi; Örd, Tiit; Heinäniemi, Merja; Kaikkonen, Minna U.; Zhang, Fenghua; Srinivasarao, Madduri; Knuuti, Juhani; Low, Philip S.; Saraste, Antti; Li, Xiang-Guo; Roivainen, Anne
- Abstract
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 [68Ga]Ga-NOTA-folate (68Ga-FOL). After determining the affinity of 68Ga-FOL using cells expressing FR-β, 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-β. 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-β–targeted tracer for imaging macrophage-associated inflammation.
- Subjects
JUNO protein; MACROPHAGES; EMISSION-computed tomography; ATHEROSCLEROSIS; RADIOACTIVITY; LABORATORY mice
- Publication
Scientific Reports, 2020, Vol 10, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-020-70394-3