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

Radiology. 2014 Jul;272(1):174-83. doi: 10.1148/radiol.14132042. Epub 2014 Apr 20.

Abstract

Purpose: 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.

Materials and 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.

Conclusion: (18)F-P3BZA PET/CT is a feasible technique for visualizing and detecting the activity of implanted RPE cells in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Autoradiography
  • Corpus Striatum
  • Female
  • Fluorine Radioisotopes / pharmacokinetics*
  • Immunohistochemistry
  • Molecular Imaging / methods*
  • Multimodal Imaging*
  • Parkinson Disease / therapy*
  • Picolinic Acids / pharmacokinetics*
  • Positron-Emission Tomography*
  • Radiopharmaceuticals / pharmacokinetics*
  • Rats
  • Rats, Wistar
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / diagnostic imaging
  • Retinal Pigment Epithelium / transplantation*
  • Staining and Labeling
  • Swine
  • Tomography, X-Ray Computed*

Substances

  • Fluorine Radioisotopes
  • N-(2-(diethylamino)ethyl)-5-fluoropicolinamide
  • Picolinic Acids
  • Radiopharmaceuticals