Page 31 - Towards personalized therapy for metastatic prostate cancer: technical validation of [18F]fluoromethylcholine

Dual-phase [18F]FCH PET/CT in prostate cancer
PSA relapse, suspected to be associated with residual or recurrent disease, was defined
as a serum concentration level above 0.2 ng/ml, after RP and after the combination
of RP with other types of therapy. A rising PSA level > 2 ng/ml above the nadir value in
patients treated by means of EBRT was considered suspect for persistent or recurrent
disease [18]. Increased serum PSA was confirmed by two consecutive exams for all
patients. The maximal time interval between performing the PET/CT scan and the last 2 PSA determination was 14 days.
Based on histology, the primary PC was classified as low (Gl <7), intermediate (Gl = 7) and high grade (Gl > 7), according to the modified Gleason Grading System [19].
Lymph node classification
We classified lymph nodes as benign or malignant using the following approach: inguinal lymph nodes with enhanced [18F]FCH uptake were considered benign since the prostatic lymph node drainage pattern does not include inguinal nodes [20–22]. Pelvic nodes with a short axis diameter ≥ 8mm were classified as malignant [23]. Additional confirmation was obtained using histopathology (whenever feasible), and with clinical follow-up of 6-12 months in all patients. Follow-up consisted of PSA measurements over time (as above mentioned) and/or evaluation of other imaging (i.e., contrast-enhanced abdominopelvic CT, pelvic MRI). We applied the following radiological criteria to classify change [24]: an increase by 30% versus initial size as progression, a decrease by 30% as regression, and intermediate values or no change in size as stable.
Therefore, malignancy was defined as a positive histopathological result; radiologically confirmed progression in size of the pertaining lymph nodes; decrease or normalization of serum PSA and radiological response after therapy, providing these were the only abnormal findings on the initial PET/CT scan; decrease or normalization of serum PSA with nodal regression after RT, with the RT field including the site of the suspected LN.
Synthesis of [18F]FCH
[18F]FCH was synthesized according to the methods proposed by DeGrado et al. [1, 25] and Iwata et al. [26], with minor modifications and by use of automated modules built in-house [27]. In short, cyclotron produced [18F]fluoride was reacted with dibromomethane, the formed [18F]fluorobromomethane was purified and used in the alkylation of 2-(dimethylamino)ethanol to obtain 2.6±0.9 GBq [18F]FCH after semi-preparative high performance liquid chromatography (HPLC) purification, reformulation in aqueous 0.9% NaCl and sterile filtration.
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