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

Objective: PET imaging with ¹⁸F-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 ¹⁸F-fluoride on ¹⁸F-FDOPA PET in NB and to implement a method to maintain low ¹⁸F-fluoride content in future studies. Methods: Automatic synthesis of ¹⁸F-FDOPA was based on the electrophilic method using TRACERlab FX_FE module. Radio-TLC was employed to determine residual ¹⁸F-fluoride levels. We analyzed the impact of residual ¹⁸F-fluoride on the images of 35 patients undergoing ¹⁸F-FDOPA PET at initial diagnosis and/or follow-ups of NB. Results: In 35 batches of ¹⁸F-FDOPA products from 9/28/2010 to 07/27/2011, the mean residual ¹⁸F-fluoride level was 4.4 % (range 0.2–19.1 %). Residual ¹⁸F-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 ¹⁸F-FDOPA imaging in NB. By applying stringent restraints in ¹⁸F-FDOPA production, including regular renewal of reagents, exclusive use  of NH₄OH, and timely replacement of HPLC column, the incidence of ¹⁸F-FDOPA batches with residual ¹⁸F-fluoride level ≥4.0 % was reduced from 33 to 4 % (P < 0.0001) during 7/30/2011–4/29/2013. Conclusion: By monitoring residual ¹⁸F-fluoride levels and keeping stringent restraint procedures, low ¹⁸F-fluoride content was achieved in most batches of ¹⁸F-FDOPA, which diminished false-positive skeletal uptake. An appropriate upper limit of ¹⁸F-fluoride level is suggested to be included in the criteria of routine quality control of ¹⁸F-FDOPA productions.