Abstract
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Objectives: Neuromelanin (NM), which is mostly concentrated in the substantia nigra (SN), is a crucial component in the brain that playing a pivotal role in neurofunction and neurodegenerative diseases such as Parkinson’s disease (PD). 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 imaging ability of 18F-P3BZA to quantitatively detect the NM in SN in healthy human volunteers.
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 healthy human volunteers (n=3), 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. PET/MRI revealed that 18F-P3BZA accumulated in SN rapidly in healthy human volunteers. Autoradiography showed significant 18F-P3BZA accumulation in healthy SN which has a high concentration of NM, while noobserved 18F-P3BZA uptake in the SN tissue of severe PD patients.
Conclusions: The 18F-P3BZA PET/MRI clearly images the neuromelanin in the substantia nigra, suggesting it is a potential probe for imaging neurological diseases associated with neuromelanin abnormal expression such as PD.