de Ruiter Ruben D, Zwama Jolien, Raijmakers Pieter G H M, Yaqub Maqsood, Burchell George L, Boellaard Ronald, Lammertsma Adriaan A, Eekhoff Elisabeth M W
Department of Endocrinology and Metabolism, Rare Bone Disease Center, Amsterdam University Medical Centers (UMC), Vrije Universiteit, Amsterdam Movement Sciences, Amsterdam, The Netherlands.
Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers (UMC), Vrije Universiteit, Amsterdam, The Netherlands.
Ann Nucl Med. 2025 Feb;39(2):98-149. doi: 10.1007/s12149-024-01991-9. Epub 2024 Dec 27.
[F]NaF PET has become an increasingly important tool in clinical practice toward understanding and evaluating diseases and conditions in which bone metabolism is disrupted. Full kinetic analysis using nonlinear regression (NLR) with a two-tissue compartment model to determine the net rate of influx (K) of [F]NaF is considered the gold standard for quantification of [F]NaF uptake. However, dynamic scanning often is impractical in a clinical setting, leading to the development of simplified semi-quantitative parameters. This systematic review investigated which uptake parameters have been used to evaluate bone disorders and how they have been validated to measure disease activity.
A literature search (in PubMed, Embase.com, and Clarivate Analytics/Web of Science Core Collection) was performed up to 28th November 2023, in collaboration with an information specialist. Each database was searched for relevant literature regarding the use of [F]NAF PET/CT to measure disease activity in bone-related disorders. The main aim was to explore whether the reported semi-quantitative uptake values were validated against full kinetic analysis. A second aim was to investigate whether the chosen uptake parameter correlated with a disease-specific outcome or marker, validating its use as a clinical outcome or disease marker.
The initial search included 1636 articles leading to 92 studies spanning 29 different bone-related conditions in which [F]NaF PET was used to quantify [F]NaF uptake. In 12 bone-related disorders, kinetic analysis was performed and compared with simplified uptake parameters. SUV (standardized uptake value) and SUV were used most frequently, though normalization of these values varied greatly between studies. In some disorders, various studies were performed evaluating [F]NaF uptake as a marker of bone metabolism, but unfortunately, not all studies used this same approach, making it difficult to compare results between those studies.
When using [F]NaF PET to evaluate disease activity or treatment response in various bone-related disorders, it is essential to detail scanning protocols and analytical procedures. The most accurate outcome parameter can only be obtained through kinetic analysis and is better suited for research. Simplified uptake parameters are better suited for routine clinical practice and repeated measurements.
[F]NaF PET已成为临床实践中理解和评估骨代谢紊乱疾病及状况的一项日益重要的工具。使用双组织房室模型通过非线性回归（NLR）进行全动力学分析以确定[F]NaF的净流入率（K），被认为是定量[F]NaF摄取的金标准。然而，动态扫描在临床环境中通常不切实际，导致了简化半定量参数的发展。本系统评价调查了哪些摄取参数已被用于评估骨疾病，以及它们如何被验证以测量疾病活动。
与信息专家合作，截至2023年11月28日进行了文献检索（在PubMed、Embase.com和科睿唯安/科学网核心合集）。在每个数据库中搜索有关使用[F]NAF PET/CT测量骨相关疾病疾病活动的相关文献。主要目的是探讨所报告的半定量摄取值是否针对全动力学分析进行了验证。第二个目的是研究所选摄取参数是否与疾病特异性结局或标志物相关，以验证其作为临床结局或疾病标志物的用途。
初步检索纳入1636篇文章，得到92项研究，涵盖29种不同的骨相关状况，其中使用[F]NaF PET定量[F]NaF摄取。在12种骨相关疾病中，进行了动力学分析并与简化摄取参数进行了比较。SUV（标准化摄取值）和SUV使用最为频繁，尽管这些值的标准化在不同研究之间差异很大。在某些疾病中，进行了各种研究来评估[F]NaF摄取作为骨代谢标志物，但遗憾的是，并非所有研究都采用相同的方法，这使得难以比较这些研究之间的结果。
当使用[F]NaF PET评估各种骨相关疾病的疾病活动或治疗反应时，详细说明扫描方案和分析程序至关重要。最准确的结局参数只能通过动力学分析获得，更适合用于研究。简化摄取参数更适合常规临床实践和重复测量。
