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Review
. 2024 Oct 10;14(10):1276.
doi: 10.3390/biom14101276.

[18F]NaF PET/CT as a Marker for Fibrodysplasia Ossificans Progressiva: From Molecular Mechanisms to Clinical Applications in Bone Disorders

Jolien Zwama  1   2   3   4 , Neeltje M Rosenberg  1   2   3   4 , Vincent A Verheij  1   3   4 , Pieter G H M Raijmakers  4   5 , Maqsood Yaqub  4   5 , Esmée Botman  1   4 , Ruben D de Ruiter  1   4   6 , Mark R Garrelfs  4   7 , Arend Bökenkamp  4   8 , Dimitra Micha  2   3   4   9 , Lothar A Schwarte  4   10 , Bernd P Teunissen  4   5 , Adriaan A Lammertsma  4   5   11 , Ronald Boellaard  4   5 , Elisabeth M W Eekhoff  1   2   3   4
Affiliations
Review

[18F]NaF PET/CT as a Marker for Fibrodysplasia Ossificans Progressiva: From Molecular Mechanisms to Clinical Applications in Bone Disorders

Jolien Zwama et al. Biomolecules. .

Abstract

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic bone disorder characterized by episodic flare-ups in connective tissue, which are frequently followed by the formation of heterotopic ossification. The absence of available plasma-soluble biomarkers for flare-ups or heterotopic bone formation poses severe challenges to the monitoring of disease activity to measure or predict disease progression. Recently, 18-fluor-sodium fluoride positron emission tomography/computed tomography ([18F]NaF PET/CT) was introduced as a potential marker for ossifying FOP activity. This review discusses the pharmacokinetics of [18F]NaF in relation to the pathophysiology of FOP, and its use as a marker of local bone metabolism in a variety of bone-related disorders. In addition, the review specifically addresses the applicability of [18F]NaF PET/CT imaging in FOP as a monitoring modality.

Keywords: 18F-sodium fluoride (18F-NaF); fibrodysplasia ossificans progressiva; heterotopic ossification; musculoskeletal development; osteoblasts; positron emission tomography/computed tomography (PET/CT); rare bone diseases.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
(A): Fused axial [18F]NaF PET/CT of the right and left knee of a patient with FOP. Tracer uptake appears as orange-to-white, with white indicating a higher metabolic activity. In the right knee, a lesion with increased focal uptake in the lateral collateral ligament is apparent, while no increased uptake is seen in the left knee. (B): A schematic overview of [18F]NaF uptake incorporation. Chondrocytes create a cartilage matrix, in which adjacent osteoblasts secrete extracellular bone matrix and regulate the mineralization of hydroxyapatite crystals. After intravenous injection, [18F]NaF travels through plasma to areas of bone metabolism. Ionic substitution then results in the replacement of an OH-group by [18F] in hydroxyapatite forming fluoroapatite.
Figure 2
Figure 2
Whole-body [18F]NaF PET maximum intensity projection (MIP) (left panel) and corresponding low-dose CT 3D reconstruction (right panel) of a patient with FOP (Nov. 2015) and consecutive scan (July 2016). [18F]NaF tracer uptake is displayed on a grey scale, with black indicating a higher tracer accumulation. [18F]NaF PET shows initially a lesion with increased tracer uptake in the upper right leg in the quadriceps muscle, while the corresponding CT shows no apparent HO. Eight months later, the increased tracer uptake in the right quadriceps muscle subsided, while the low-dose CT shows a large HO lesion, analogous to the site of increased tracer uptake in Nov. 2015. (Reprinted from Bone, Vol. 109, Eekhoff EMW, Botman E, Coen Netelenbos J, et al., [18F]NaF PET/CT scan as an early marker of heterotopic ossification in fibrodysplasia ossificans progressiva, 143–146, Copyright (2018), with permission from Elsevier.).
See this image and copyright information in PMC

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