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


METHODS
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.


RESULTS
(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.


CONCLUSIONS
(18)F-P3BZA PET/CT is a feasible technique for visualizing and detecting the activity of implanted RPE cells in vivo.
From the Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University, 1201 Welch Rd, Lucas Center, Room P095, Stanford, CA 94305-5484 (L.B., R.L., H.L., Z.C.); Molecular Imaging Center, Department of Radiology, The 4th Hospital of Harbin Medical University, Harbin, Heilongjiang, P.R. China (L.B., R.L., B.S.); and Departments of Genetics (W.F., D.V.) and Neurosurgery (X.X., H.Z.), School of Medicine, Stanford University, Stanford, Calif.
Lihong
L
Bu
Renfei
R
Li
Hongguang
H
Liu
Wei
W
Feng
Xiaoxing
X
Xiong
Heng
H
Zhao
Douglas
D
Vollrath
Baozhong
B
Shen
Zhen
Z
Cheng
D000818:Animals; D001345:Autoradiography; D003342:Corpus Striatum; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D007150:Immunohistochemistry; D057054:Molecular Imaging / Q000379:methods*; D064847:Multimodal Imaging; D010300:Parkinson Disease / Q000628:therapy*; D010848:Picolinic Acids / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000000981:diagnostic imaging / Q000637:transplantation*; D013194:Staining and Labeling; D013552:Swine; D014057:Tomography, X-Ray Computed
D005462:Fluorine Radioisotopes; C000591167:N-(2-(diethylamino)ethyl)-5-fluoropicolinamide; D010848:Picolinic Acids; D019275:Radiopharmaceuticals