Impact of residual [18F]Fluoride in diagnosis of neuroblastoma patients from [18F]FDOPA routine production

Objectives [18F]FDOPA(FDOPA) has been used in the diagnosis of Neuroblastoma (NB) by targeting the overexpression of amino acid decarboxylase in NB cells. A great portion of NB patients may have skeletal metastases. Detection of [18F]F- is not included in the USP monograph specification of FDOPA. The residual [18F]F- content in FDOPA production may result in bony uptake instead of tumor uptake. The aim of our study is to assess the impact of residual [18F]F- in NB diagnosis and to implement a method to maintain low [18F]F- content.

Methods Automatic synthesis of FDOPA was based on the electrophilic method using TRACERlab FXFE module. Radio-TLC method was employed with RP-18 TLC plate for determination of the residual [18F]F- level. We recruited 60 patients (age 0.1-18 years) with NB to receive FDOPA PET at initial diagnosis and follow-ups. The residual [18F]F- levels in each FDOPA batch were correlated with the skeleton uptakes in PET images.

Results From Sep. 2010 to Mar. 2012, the residual [18F]F- levels were in the range of 0.2%-19.1% in 82 batches of production. 181 FDOPA PET scans were performed. Comparing the PET images of same patients in different studies, we found that the residual [18F]F- levels (>4.0%) would show significant growth plate uptake and may disturb the interpretation. 80% of FDOPA productions showed that the [18F]F- levels were >4.0 %. To achieve a low level of residual [18F]F-, we replaced the HPLC column and chemical reagents (NH4(aq)) every 30 runs or when [18F]F- level >3.0%. Up to Dec. 2012, the level of residual [18F]F- were kept <4.0% in all FDOPA batches (n=60).

Conclusions By monitoring the residual [18F]F- level in final [18F]FDOPA product and keeping the stringent procedures, we can keep the [18F]F- content to be lower than 4% in all [18F]FDOPA productions. We expect that there will be no more significant bony uptake in future studies. Furthermore, the appropriate level of [18F]F- (<4.0%) maybe needed to be included in the criteria of routine quality control of [18F]FDOPA.