Fusion PET/MRI of neuromelanin in substantia nigra using 18F-P3BZA in Patients with Parkinson’s Disease: preliminary results
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更新:2021-11-05 16:47:55
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摘要
Background: The degeneration of melanized dopaminergic neurons in substantia nigra (SN) is a hallmark of several neurodegenerative diseases such as Parkinson’s disease (PD). A tracer for accurate assessment of neuromelanin (NM) level in SN in vivo is thus required, but until now it still represents as an unmet medical need.
Purpose:We previously demonstrated that N-(2-(diethylamino)-ethyl)-18F-5-fluoropicolinamide (18F-P3BZA) is a promising positron emission tomography (PET) probe for imaging melanin in living subject. In this study, we aim to investigate the feasibility of 18F-P3BZA PET combined with MRI for quantitative detection of neuromelanin (NM) in SN in healthy human volunteers and patients with parkinson’s disease.
Materials and Methods: Specific binding assay of 18F-P3BZA to NM was performed by testing the cell uptake of the probe in neuromelanotic PC12 cells, melanin-rich B16F10 cells, and amelanotic SKOV3 cells at 15, 30, 60, and 120 minutes post-incubation. Ex vivo biodistribution studies were also conducted in melanoma or amelanoma xenografts. 18F-P3BZA PET was performed in 10 healthy human volunteers (median age, 31 years; range, 27–35 years; 3 men) and 30 patients with parkinson’s disease, accompanied with magnetic resonance imaging (MRI) for co-registration. Autoradiography of human brain slides samples was performed accompanied with gross midbrain photos and Fontana-Masson stains for co-registration of SN neuromelanin.
Results:18F-P3BZA accumulation in neuromelanotic PC12 cells and melanotic-rich melanoma cells were significantly higher than that in amelanotic cells. Fusion PET/MRI revealed that 18F-P3BZA accumulated in SN rapidly in healthy human volunteers. Autoradiography showed significant 18F-P3BZA accumulation in healthy SN which contains a high concentration of NM, while no observed 18F-P3BZA uptake outside SN zones in the midbrain. PET/CT scans revealed that the activity of SN in patients with PD decreased compared to healthy controls, as evidenced by a reduction in (18)F-P3BZA uptake (1.36% ID/g ± 0.14 and 3.75% ID/g ± 0.52, respectively; P < .05).
Conclusion The 18F-P3BZA PET is feasible to visualize the nigral neuromelanin in substantia nigra, suggesting it may be used a potential tracer for assessment of pigmented neuronal loss in PD.
关键字
Substantia nigra;neuromelanin;18F-P3BZA;positron emission tomography;Magnetic resonance imaging (MRI);Parkinson’s disease
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