Intrastriatal transplantation of retinal pigment epithelial cells for the treatment of Parkinson disease: in vivo longitudinal molecular imaging with 18F-P3BZA PET/CT.

Abstract

To evaluate the performance of N-[2-(diethylamino)ethyl]-(18)F-5-fluoropicolinamide ((18)F-P3BZA) for visualizing porcine retinal pigment epithelium (pRPE) cells transplanted in the striatum for the treatment of Parkinson disease and to monitor the long-term activity of implanted pRPE cells by means of (18)F-P3BZA positron emission tomography (PET)/computed tomography (CT) in vivo. Animal work was conducted in accordance with the administrative panel on laboratory animal care. In vitro cell uptake of (18)F-P3BZA was determined with incubation of melanotic pRPE or amelanotic ARPE-19 cells with (18)F-P3BZA. To visualize the implanted pRPE cells in vivo, normal rats (four per group) were injected with pRPE or ARPE-19 cells attached to gelatin microcarriers in the left striatum and with control gelatin microcarriers in the right striatum and followed up with small animal PET/CT. Longitudinal PET/CT scans were acquired in 12 rats up to 16 days after surgery. Postmortem analysis, which included autoradiography and hematoxylin-eosin, Fontana-Masson, and immunofluorescence staining, was performed. Data were compared with the Student t test, analysis of variance, and regression analysis. (18)F-P3BZA accumulated in pRPE cells effectively (3.48% of the injected dose [ID] per gram of brain tissue ± 0.58 at 1 hour after injection of the probe at 2 days after surgery in vivo) but not in control ARPE-19 cells (P < .05). Longitudinal PET/CT scans revealed that the activity of implanted pRPE cells decreased over time, as evidenced by a reduction in (18)F-P3BZA uptake (3.39% ID/g ± 0.18, 2.49% ID/g ± 0.41, and 1.20% ID/g ± 0.13 at days 2, 9, and 16, respectively; P < .05). Postmortem analysis helped confirm the results of in vivo imaging. (18)F-P3BZA PET/CT is a feasible technique for visualizing and detecting the activity of implanted RPE cells in vivo.