PFKFB3, a glycolysis-related enzyme upregulated in inflammatory conditions and angiogenesis, is an emerging target for diagnosis and therapy of atherosclerosis. The fluorinated phenoxindazole [ 18 F]ZCDD083 was synthesised, radiolabelled in 17 ±5% radiochemical yield and >99% radiochemical purity, and formulated for pre-clinical PET/CT imaging in mice. In vivo stability analysis showed no significant metabolite formation. Biodistribution studies showed high blood pool activity and slow hepatobiliary clearance. Significant activity was detected in the lung 2 h post-injection (pi) (11.0 ±1.5 %ID/g), while at 6 h pi no pulmonary background was observed. Ex vivo autoradiography at 6 h pi showed significant high uptake of [ 18 F]ZCDD083 in the arch region and brachiocephalic artery of atherosclerotic mice, and no uptake in control mice, matching plaques distribution seen by lipid staining along with PFKFB3 expression seen by immunofluorescent staining. In vivo PET scans showed higher aortic region uptake of [ 18 F]ZCDD083 in atherosclerotic ApoE -/-Fbn1 C1039G+/than in control mice (0.78 ± 0.05 vs 0.44 ± 0.09 %ID/g). [ 18 F]ZCDD083 was detected in aortic arch and brachiocephalic artery of ApoE -/-(with moderate atherosclerosis) and ApoE -/-Fbn1 C1039G+/-(with severe, advanced atherosclerosis) mice, suggesting this tracer may be useful for the non-invasive detection of atherosclerotic plaques in vivo.
The DAMIC-M (DArk Matter In CCDs at Modane) experiment employs thick, fully depleted silicon charged-coupled devices (CCDs) to search for dark matter particles with a target exposure of 1 kg-year. A novel skipper readout implemented in the CCDs provides single electron resolution through multiple non-destructive measurements of the individual pixel charge, pushing the detection threshold to the eV-scale. DAMIC-M will advance by several orders of magnitude the exploration of the dark matter particle hypothesis, in particular of candidates pertaining to the so-called “hidden sector.” A prototype, the Low Background Chamber (LBC), with 20g of low background Skipper CCDs, has been recently installed at Laboratoire Souterrain de Modane and is currently taking data. We will report the status of the DAMIC-M experiment and first results obtained with LBC commissioning data.
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