Page 22 - Towards personalized therapy for metastatic prostate cancer: technical validation of [18F]fluoromethylcholine

Chapter 1
Summarizing, PET imaging is a promising approach, both in clinical and research applications. PET allows for quantitative measurements with high sensitivity, yielding non-invasive information about biological processes through the body. Standard methods of PET quantification are difficult to implement in daily clinical practice. Simplified methods of quantification are available but should be validated versus the standard methods. To distinguish biological change from noise, repeatability of a tracer should be known. Due to the increasing role of [18F]FCH PET in PC, clinically feasible protocols, based on reliable and repeatable indices characterizing tumor activity, are essential for monitoring response to therapy. Complex quantitative analysis methods are likely to become widely available in clinical setting. This enhances the potential of radiolabeled choline PET to “tailor” treatment by timely evaluating the effectiveness of therapy, thus avoiding ineffective, costly or risky treatments.
Outline of this thesis
The aim of the present thesis was to investigate the role of [18F]FCH as a potential response evaluation tool in patients with prostate cancer.
In chapter two we studied the diagnostic role of dual-phase [18F]FCH PET/CT in a clinical setting. Therefore, we analyzed whether time-trends of enhanced [18F]FCH in lymph nodes of PC patients can help to discriminate reactive from malignant ones, and whether single time point SUV measurements may also suffice.
In chapter three we studied an alternative potential application of [18F]FCH in metastatic PC. In this context, we investigated whether uptake of [18F]FCH, in comparison with [18F] FDG, accurately reflects chemotherapy efficacy at the tumor cell level in PC.
In chapter four we investigated how [18F]FCH can be reliably measured in a routine clinical setting. For this purpose, pharmacokinetic modeling of dynamic PET data in combination with arterial blood sampling was used to determine the appropriate plasma input compartment model for [18F]FCH. In addition, the validity of using simplified methods for quantification of [18F]FCH was assessed.
In chapter five we investigated whether the simplified methods for [18F]FCH uptake measuring, as proposed in chapter four, are repeatable in daily practice. For this purpose, we assessed repeatability of various quantitative [18F]FCH parameters in PC, also including metabolic tumor volume and total lesion choline uptake.
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