Performance of simplified methods for quantification of [18F]NaF uptake in fibrodysplasia ossificans progressiva

R. D. de Ruiter, Esmée Botman, B. Teunissen, Adriaan A. Lammertsma, Ronald Boellaard, Pieter G. Raijmakers, Lothar A. Schwarte, Jakko A. Nieuwenhuijzen, Dinko Gonzalez Trotter, E. M. Eekhoff, M. Yaqub
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Abstract

Fibrodysplasia Ossificans Progressiva (FOP) is a rare, genetic disease in which heterotopic bone is formed in muscles, tendons and ligaments throughout the body. Disease progression is variable over time and between individuals. 18F-fluoride uptake in newly formed bone can be evaluated using [18F]NaF (i.e., sodiumfluoride) PET/CT, identifying active areas of bone formation in FOP. The purpose of this study was to assess the performance of various semi-quantitative methods with full kinetic analysis.Seven patients (age range: 20–31 years) with FOP underwent dynamic [18F]NaF scans at baseline and after one year. [18F]NaF uptake was measured in aorta descendens, vertebrae, heterotopic bone lesions and metabolically active regions on PET, and quantified using nonlinear regression (NLR) analysis together with standardized uptake value (SUV) and target-to-blood ratio (TBR). SUV was on measured the 40–45 min frame of the dynamic sequence (SUV40–45) and on the subsequent static sweep (SUVStatic). Correlations between and SUV40–45 and NLR-derived Ki were comparable when normalized to body weight (r = 0.81, 95% CI 0.64–0.90), lean body mass (r = 0.79, 95% CI 0.61–0.89) and body surface area (r = 0.84, 95% CI 0.70–0.92). Correlation between TBR40–45 and NLR-derived Ki (r = 0.92, 95% CI 0.85–0.96) was higher than for SUV40–45. Correlation between TBR40–45 and NLR-derived Ki was similar at baseline and after one year (r = 0.93 and 0.94). The change in TBR40–45 between baseline measurement and after one year correlated best with the change in NLR-derived Ki in the PET-active lesions (r = 0.87).The present data supports the use of TBR for assessing fluoride uptake in PET-active lesions in FOP.Sub-study of the Lumina-1 trial (clinicaltrials.gov, NCT03188666, registered 13-06-2017).
用于量化渐进性骨化性纤维软化症[18F]NaF 摄取的简化方法的性能
纤维增生性骨质疏松症(FOP)是一种罕见的遗传性疾病,患者全身的肌肉、肌腱和韧带都会形成异位骨。疾病的进展随时间和个体差异而变化。使用[18F]NaF(即氟化钠)PET/CT 可评估新形成骨中的 18F -氟化物摄取量,从而确定 FOP 中骨形成的活跃区域。本研究的目的是评估各种半定量方法与全动力学分析的性能。七名 FOP 患者(年龄范围:20-31 岁)在基线和一年后接受了动态 [18F]NaF 扫描。在 PET 上测量了主动脉降部、椎骨、异位骨病变和代谢活跃区域的[18F]NaF 摄取量,并使用非线性回归(NLR)分析以及标准化摄取值(SUV)和靶血比(TBR)进行量化。SUV是在动态序列的40-45分钟帧(SUV40-45)和随后的静态扫描(SUVStatic)中测量的。当与体重(r = 0.81,95% CI 0.64-0.90)、瘦体重(r = 0.79,95% CI 0.61-0.89)和体表面积(r = 0.84,95% CI 0.70-0.92)归一化时,SUV40-45 和 NLR 导出 Ki 之间的相关性相当。TBR40-45 与 NLR 导出 Ki 之间的相关性(r = 0.92,95% CI 0.85-0.96)高于 SUV40-45。基线时和一年后,TBR40-45 与 NLR 派生 Ki 之间的相关性相似(r = 0.93 和 0.94)。TBR40-45在基线测量和一年后的变化与PET活性病变中NLR衍生Ki的变化相关性最好(r = 0.87)。本数据支持使用TBR评估FOP PET活性病变中的氟吸收。
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