Impact of residual (18)F-fluoride in (18)F-FDOPA for the diagnosis of neuroblastoma

Ann Nucl Med. 2015 Jul;29(6):489-98. doi: 10.1007/s12149-015-0970-x. Epub 2015 Apr 8.

Abstract

Objective: PET imaging with (18)F-FDOPA has been successfully applied in the diagnosis and surveillance of neuroblastoma (NB) by targeting the overexpression of aromatic L-amino acid decarboxylase. This study aims to assess the impact of residual (18)F-fluoride on (18)F-FDOPA PET in NB and to implement a method to maintain low (18)F-fluoride content in future studies.

Methods: Automatic synthesis of (18)F-FDOPA was based on the electrophilic method using TRACERlab FXFE module. Radio-TLC was employed to determine residual (18)F-fluoride levels. We analyzed the impact of residual (18)F-fluoride on the images of 35 patients undergoing (18)F-FDOPA PET at initial diagnosis and/or follow-ups of NB.

Results: In 35 batches of (18)F-FDOPA products from 9/28/2010 to 07/27/2011, the mean residual (18)F-fluoride level was 4.4 % (range 0.2-19.1 %). Residual (18)F-fluoride level ≥4.0 % was associated with dense uptake in the growth plates, skull, and pelvis on PET scans, which may interfere with the interpretation of (18)F-FDOPA imaging in NB. By applying stringent restraints in (18)F-FDOPA production, including regular renewal of reagents, exclusive use of NH4OH, and timely replacement of HPLC column, the incidence of (18)F-FDOPA batches with residual (18)F-fluoride level ≥4.0 % was reduced from 33 to 4 % (P < 0.0001) during 7/30/2011-4/29/2013.

Conclusion: By monitoring residual (18)F-fluoride levels and keeping stringent restraint procedures, low (18)F-fluoride content was achieved in most batches of (18)F-FDOPA, which diminished false-positive skeletal uptake. An appropriate upper limit of (18)F-fluoride level is suggested to be included in the criteria of routine quality control of (18)F-FDOPA productions.

MeSH terms

  • Bone Neoplasms / diagnosis
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / genetics
  • Bone Neoplasms / secondary
  • Child
  • Child, Preschool
  • Chromatography
  • Dihydroxyphenylalanine / analogs & derivatives*
  • Female
  • Fluorine Radioisotopes*
  • Follow-Up Studies
  • Humans
  • Infant
  • Male
  • Multimodal Imaging
  • N-Myc Proto-Oncogene Protein
  • Neuroblastoma / diagnosis*
  • Neuroblastoma / diagnostic imaging*
  • Neuroblastoma / genetics
  • Neuroblastoma / pathology
  • Nuclear Proteins / genetics
  • Oncogene Proteins / genetics
  • Positron-Emission Tomography*
  • Radiopharmaceuticals*
  • Tomography, X-Ray Computed
  • Whole Body Imaging

Substances

  • Fluorine Radioisotopes
  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins
  • Oncogene Proteins
  • Radiopharmaceuticals
  • fluorodopa F 18
  • Dihydroxyphenylalanine