Thesis

183 Denosumab reduces lesional Fluoride skeletal burden on Na[18F]F PET-CT Introduction Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS) is caused by a postzygotic activating mutation of the α-subunit of the stimulatory G-protein (Gsα) [1] causing overproduction of cAMP in affected cells of the osteogenic lineage, leading to the accelerated production of bone marrow stromal cells, whilst inhibiting the differentiation of these progenitor cells into mature osteoblasts. Despite expressing early osteoblast biomarkers such as alkaline phosphatase (ALP), these immature cells are dysfunctional, leading to the laying down of fibro-osseous tissue that is undermineralized, of poor quality and of disturbedmicro-architecture [1]. 99mTc-radiolabelled bisphosphonate bone scintigraphy (BS) is the most widely used molecular imaging method for assessing FD-burden using the skeletal burden score (SBS) [2]. The SBS is the weighted sum of the per-segment estimation of the percentage of affected normal bone volume on planar BS. The weighting factors used are based on average representation of that segment to a healthy adult skeleton, however this might be an underestimation for FD-affected expansile segments, e.g. in the ribs [2-4]. Despite that BS is widely used as an adjunct for primary characterization of FD, the use in follow-up remains controversial: Collins, et al. reported no change in BS and SBS after bisphosphonate treatment whereas others report clinical improvement in combination with a skeletal burden response in FD [2, 5]. Still, so far there are no objective local parameters available to assess lesional response to treatment. Granting the use of Na[18F]F PET-CT in benign disease is still scarce, the combination of substantive advantages over other techniques, improving availability and decreasing costs, has led to an increasingly renewed interest in this tracer beyond bone metastases [6-10]. We and others recently showed that positron emission tomography with integrated computed tomography using sodium fluoride-18 (Na[18F]F PET-CT) provides quantitative parameters of disease burden using the volume-based parameters Fluoride Tumor Volume (FTV) and Total Lesion Fluorination (TLF) that has a high correlation with serum biomarkers of bone turnover (BTMs): P1NP, ALP, N‐ telopeptides and osteocalcin [3, 4]. TLF is based on both the volume of increased bone activity (FTV) and its mean level of bone activity (mean standardized Na[18F]F uptake value, SUVmean). In previous observations high correlations betweenmolecular imaging and BTMs were mainly driven by the volumetric parameter FTV, without a significant contribution of the intensity parameter SUVmean, for which the optimal normalization method is still under debate [11, 12]. Therefore FTV is to be preferred over the compound parameter TLF. Compared to standard 99mTc-radiolabelled bisphosphonate BS with hybrid single photon emission tomography and CT (SPECT8

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