Validation of quantitative [¹⁸F]NaF PET uptake parameters in bone diseases: a systematic review

[¹⁸F]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_i) of [¹⁸F]NaF is considered the gold standard for quantification of [¹⁸F]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 [¹⁸F]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 [¹⁸F]NaF PET was used to quantify [¹⁸F]NaF uptake. In 12 bone-related disorders, kinetic analysis was performed and compared with simplified uptake parameters. SUV_mean (standardized uptake value) and SUV_max were used most frequently, though normalization of these values varied greatly between studies. In some disorders, various studies were performed evaluating [¹⁸F]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 [¹⁸F]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.