Page 86 - Quantitative Imaging of Small Tumours with Positron Emission Tomography

Introduction The androgen receptor (AR) axis plays a central role in hormone sensitive as well as castrate resistant prostate cancer (CRPC) (1). In the last decades several AR signalling inhibitor (ARSi) therapies have been developed and approved for treatment of metastatic (m)CRPC patients (2-5). Results of initial treatment with ARSi therapies (e.g. enzalutamide and abiraterone) are excellent, with mild toxicity profiles. Unfortunately, initial treatment response and response durability are variable, and response to second-line ARSi therapies is often short (3,5). Therefore, a predictive biomarker for response to these ARSi drugs is urgently needed. 4 Currently used imaging modalities (e.g. CT and bone scintigraphy) for restaging and detection of disease progression in CRPC are not suited for this purpose (6). 18F-fluorodihydrotestosterone ([18F]FDHT) positron emission tomography- computed tomography (PET-CT) directly targets the AR in whole body imaging (7,8). Hereby it can assess AR-status on a lesion-by-lesion level allowing for characterization of AR expression and its intra-patient heterogeneity in-vivo(9). This may not only enable prognostication for ARSi therapies, but also facilitate novel AR-targeted drug development (10,11). Recently, technical validation studies on the optimal simplified metrics and their repeatability have been performed and clinical studies evaluating the value of 18F-FDHT PET/CT as imaging biomarker in clinical setting are ongoing (8,12). Crucial elements of validation and clinical implementation of novel oncologic PET tracers and their imaging protocols are patient burden and cost of imaging. The latter two should be as low as possible, whilst maintaining high quantitative and qualitative accuracy for clinical purposes such as prediction or monitoring of treatment response. Until now, whole-body [18F]FDHT PET-CT studies have been acquired at 3-4 minutes per bed position, resulting in a typical in-scanner time of about 30 min for a single scan session (7,12). As mCPRC patients often have extensive (painful) metastatic disease, frequently involving the spine, reducing acquisition time could diminish patient burden, reduce cost of imaging, and improve department efficiency. This requires that the effect of count statistics on the performance of [18F]FDHT PET-CT is known. For [18F]FDG PET- CT it has been shown that reducing acquisition times may reduce image quality, but does not necessarily affect lesion detection rates (13,14). The finite spatial resolution of current PET scanners lead to blurring of images and cause partial-volume effects. Therefore, the EANM Research Ltd. [18F]FDHT PET repeatability 85