Page 29 - Towards personalized therapy for metastatic prostate cancer: technical validation of [18F]fluoromethylcholine

Dual-phase [18F]FCH PET/CT in prostate cancer
INTRODUCTION
Choline-based PET has proven value in several neoplasms, and especially in prostate
cancer (PC) [1, 2]. [18F]FCH PET/CT seems to become a useful imaging tool to solve the
clinical problem of rising serum prostate-specific antigen (PSA) after initially treated
PC [3-5], with PET/CT sensitivity being proportionally related to the PSA level [6, 7]. 2
Choline is the precursor of phosphatidylcholine, an essential phospholipid of cell membranes. The phosphorylation process is catalyzed by choline kinase (CK) [2]. In PC, enhanced choline uptake is explained by both increased mitogenic activity as well as up regulation of CK [8]. However, the signal is not tumor specific [9, 10]. Since biopsy of presumed regional lymph node metastases is often not trivial due to their localization in PC, false positive readings may induce serious problems in the clinical context.
Both [18F] and [11C]-labeled choline derivates have been developed and studied as possible metabolic imaging tools in the detection of primary PC, regional LN and distant metastases [11, 12]. The main advantages of [18F] over [11C]-labeled tracers are the longer half-life (110 min versus 20 min) and a better spatial resolution due to the shorter positron range of 18F. However, [18F]choline is excreted in urine [13] and this can compromise the interpretation of the pelvic area. Since [18F]FCH is rapidly cleared from the blood pool, acquisition protocols have been designed with imaging of the pelvis prior to bladder filling (within minutes after injection), followed by a whole body scan after e.g., 30 min [1, 14–16] – the dual-phase protocol. Patterns of tracer uptake as a function of time have shown to be helpful in discriminating intraprostatic tracer uptake [8, 15] as well as sites of suspected haematogeneous metastases [17].
It was suggested that increasing or stable [18F]FCH uptake over time (3-7 min versus 30-60 min after injection) was compatible with malignancy, while a decreasing tracer uptake is associated with benign status [8, 15, 17]. For lymph node assessment this hypothesis has not been validated. Beheshti et al. [8] described an interesting early [18F] FCH wash-out pattern of false-positive LN in the preoperative setting of 130 patients with high and intermediate risk for disseminated PC. This phenomenon was deemed highly important for the differentiation of malignant versus benign nodes. However, the study could not support this finding with a statistically relevant number of lesions.
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