Page 21 - Towards personalized therapy for metastatic prostate cancer: technical validation of [18F]fluoromethylcholine

restaging of PC in case of biochemical relapse, with a diagnostic performance that 1 appears to improve with increasing PSA level, although it is not recommended for
routine use when the PSA level is less than 1 ng/mL [36]. A systematic review and meta-
analysis [43] on the role of choline PET or PET/CT by biochemical relapse of PC showed
a pooled sensitivity and specificity to identify all recurrent/ metastatic localizations (prostatic region, bone, or lymph node) of 86% (95% CI 83–88%) and 93% (95% CI 90–95%), respectively.
If uptake of radiolabeled choline would reflect viable tumor tissue, changes over time of the choline signal might serve as a measure of response to therapy. For monitoring response to systemic treatment in metastasized PC, however, accurate quantification is required. To date, [18F]FCH biodistribution and radiation dosimetry have been studied [40, 44–46], but full kinetic analysis has not yet been reported.
Response evaluation and prediction in prostate cancer
The actual response to (chemo)therapeutic regimens in individual PC patients is variable. It is important to monitor therapeutic (in)efficacy in time, to prevent patients from undergoing futile and expensive therapy for too long, since alternative and potentially effective drugs are available. Presently, monitoring of progression is based on a response metrics construct requiring various diagnostic tests, including PSA measurement, CT and bone scintigraphy [47]. The limitations of the current approach are related to the heterogeneity of metastasized PC (i.e., coexistence of androgen sensitive and insensitive components with different impact on e.g., PSA [48]) and to its skeletal predominance (with bone- and CT-scans having difficulties in timely and accurately detecting response). Therefore, there is a clear need for alternative and more accurate response monitoring methods [49–51].
With each new radiopharmaceutical the challenge is to validate reliable simplified quantitative procedures, applicable in daily clinical practice, in WB setting. Whether [18F]FCH could also be employed in monitoring treatment response in PC patients receiving docetaxel and cabazitaxel therapy is unclear. Definitive data from clinical studies have not yet become available. Nevertheless, experiments in-vitro have shown promising results on the use of PET tracers to monitor anti-androgen treatment or chemotherapy [52, 53].
Introduction and outline of the thesis
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