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 [ 68 Ga]Ga-notAfolate (68 Ga-FOL). After determining the affinity of 68 Ga-FOL using cells expressing FR-β, we studied atherosclerotic mice with 68 Ga-FOL and 18 F-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 68 Ga-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 68 Ga-FOL with high radiochemical purity and moderate molar activity. Cell binding studies revealed that 68 Ga-FOL had 5.1 nM affinity for FR-β. Myocardial uptake of 68 Ga-FOL was 20-fold lower than that of 18 F-FDG. Autoradiography and immunohistochemistry of the aorta revealed that 68 Ga-FOL radioactivity co-localized with Mac-3-positive macrophage-rich atherosclerotic plaques. The plaqueto-healthy vessel wall ratio of 68 Ga-FOL was significantly higher than that of 18 F-FDG. Blocking studies verified that 68 Ga-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 68 Ga-FOL represents a promising new FR-β-targeted tracer for imaging macrophage-associated inflammation.

Purpose Photoperiod determines the metabolic activity of brown adipose tissue (BAT) and affects the food intake and body mass of mammals. Sympathetic innervation of the BAT controls thermogenesis and facilitates physiological adaption to seasonal changes, but the exact mechanism remains elusive. Previous studies have shown that central opioid signaling regulates BAT thermogenesis, and that the expression of the brain mu-opioid receptor (MOR) varies seasonally. Therefore, it is important to know whether MOR expression in BAT shows seasonal variation. Methods We determined the effect of photoperiod on BAT MOR availability using [11C]carfentanil positron emission tomography (PET). Adult rats (n = 9) were repeatedly imaged under various photoperiods in order to simulate seasonal changes. Results Long photoperiod was associated with low MOR expression in BAT (β =  − 0.04, 95% confidence interval: − 0.07, − 0.01), but not in muscles. We confirmed the expression of MOR in BAT and muscle using immunofluorescence staining. Conclusion Photoperiod affects MOR availability in BAT. Sympathetic innervation of BAT may influence thermogenesis via the peripheral MOR system. The present study supports the utility of [11C]carfentanil PET to study the peripheral MOR system.