Novel Application of 18F-NaF PET/CT Imaging for Evaluation of Active Bone Remodeling in Diabetic Patients With Charcot Neuropathy: A Proof-of-Concept Report

Abstract

Charcot neuropathic osteoarthropathy (CN) is a serious and potentially limb-threatening complication for patients with diabetes mellitus and peripheral arterial disease. In recent decades, nuclear medicine-based approaches have been used for non-invasive detection of CN; however, to date, a positron emission tomography (PET) radionuclide specifically focused on targeted imaging of active bone remodeling has not been explored or validated for patients with CN. The radionuclide 18F-sodium fluoride (NaF) has historically been used as a bone imaging probe due to its high sensitivity for targeting hydroxyapatite and bone turnover, but has not been applied in the context of CN. Therefore, the present study focused on novel application of 18F-NaF PET/computed tomography (CT) imaging to three clinical cases of CN to evaluate active bone remodeling at various time courses of CN. PET/CT imaging in all 3 cases demonstrated focal uptake of 18F-NaF in the bones of the feet afflicted with CN, with bone retention of 18F-NaF persisting for up to 5 years following surgical reconstruction of the foot in two cases. On a group level, 18F-NaF bone uptake in the CN foot was significantly higher compared to the healthy, non-CN foot (p = 0.039). 18F-NaF PET/CT imaging may provide a non-invasive tool for monitoring active bone remodeling in the setting of CN, thereby offering novel opportunities for tracking disease progression and improving treatment and surgical intervention.

Keywords: bone remodeling; charcot; computed tomography; positron emission tomography; sodium fluoride.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Tram, Chou, Patel, Ettefagh, Go, Atway and Stacy.

Figures

Figure 1

Multimodality imaging evaluation of a 65-year old male patient with a history of Charcot foot, type 2 DM, and PAD. X-rays acquired at (A) the time of external fixation and (B) 5 years after surgery reveal the architecture of the foot. (C) Maximum intensity projection (MIP) images and (D) axial, sagittal, and coronal 18F-NaF PET/CT images of the foot 5 years after surgery demonstrate focal increased uptake of 18F-NaF in the bones of the foot, indicating ongoing physiological remodeling of the afflicted foot 5 years after surgical reconstruction.

Figure 2

Imaging assessment of a 49-year old female patient with a history of right foot Charcot deformity. X-rays were acquired at (A) the time of navicular bone removal and (B) 5 years after surgical reconstruction of the foot. (C) MIP and (D) PET/CT images acquired 5 years after surgery revealed heterogeneous boney uptake of 18F-NaF and suggested potential for ongoing remodeling of the foot.

Figure 3

Imaging evaluation of 40-year old male patient with history of Charcot joint of the right ankle. (A) X-rays acquired 9 months after surgical reconstruction revealed stable bone architecture. (B) MIP and (C) PET/CT images acquired 9 months after surgery demonstrated focal uptake of 18F-NaF in the region of the surgically reconstructed ankle impacted by CN, suggesting ongoing remodeling of the bones of the ankle.

Figure 4

CT image-guided segmentation of the bones of the foot and quantitative 18F-NaF PET/CT image analysis. (A) Semiautomated segmentation of the bones of the foot and ankle (bone VOI outlined in red). (B) Quantitative analysis of PET/CT imaging demonstrated significantly higher bone uptake of 18F-NaF in the CN foot compared to the healthy non-CN foot. N = three patients. Values represent means ± SD.