Heterogeneous bone manifestations in a patient with Gaucher disease demonstrated by ¹⁸F-FDG positron emission tomography/computed tomography (PET/CT) and Al¹⁸F-FAPI-04 PET/CT: a case description

Introduction

Gaucher disease is a rare genetic disease with diverse bone manifestations. Al¹⁸F-fibroblast activation protein inhibitor (FAPI)-04 positron emission tomography/computed tomography (PET/CT) and ¹⁸F-fluorodeoxyglucose (FDG) PET/CT can evaluate functional and anatomic abnormalities within a whole-body scan, which can help in diagnosis, disease burden evaluation, and biopsy guidance of Gaucher disease. Studies based on PET/CT to evaluate Gaucher disease are scarce (1,2). In this case, we reported a patient with Gaucher disease who demonstrated heterogeneous bone disease at different sites.

Case presentation

A 34-year-old male presented with pain in the right hip. Multiple imaging methods were applied to figure out the reason of the symptom, including X-ray, magnetic resonance imaging (MRI), bone scan, CT, Al¹⁸F-FAPI-04 PET/CT and ¹⁸F-FDG PET/CT. Multiple bone lesions were revealed by these examinations and biopsies targeting bone lesions were performed twice. However, the cause of the disease could not be confirmed. Finally, the patient was diagnosed with Gaucher disease 8 months later by genetic testing [GBA:NM_001005741.3c.1448T>C(p.Leu483Pro), 1504C>T(p.Arg502Cys)] and decreased glucocerebrosidase (0.86 µmol/L/h, normal range: 1.19–22.23 µmol/L/h). Gaucher disease is a rare genetic disease with diverse bone manifestations, including bone marrow infiltration, cortical bone thinning, osteonecrosis and osteosclerosis (3). As fibrosis and chronic inflammation are present in pathology (4), Al¹⁸F-FAPI-04 PET/CT and ¹⁸F-FDG PET/CT can evaluate functional and anatomic abnormalities at the same time. This patient received ¹⁸F-FDG PET/CT (Figure 1) and Al¹⁸F-FAPI-04 PET/CT (Figure 2) within 1 month, which revealed heterogeneous bone disease. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Figure 1 ¹⁸F-FDG PET/CT of a patient with Gaucher disease. Maximum intensity projection (A,B) showed intense and uneven uptake in multiple bones. Mildly elevated uptake of ¹⁸F-FDG can also be observed in spleen. Axial PET (C), CT (D), and PET/CT fusion (E) of humeral head showed cortical bone thinning, dilation of bone marrow cavity and intense uptake of ¹⁸F-FDG in bone marrow (arrows). Coronal PET (F,I), CT (G,J), and PET/CT fusion (H,K) of femur and tibia showed osteosclerosis which exhibited slight ¹⁸F-FDG uptake and dilation of bone marrow cavity with intense ¹⁸F-FDG uptake. Axial PET (L), CT (M), and PET/CT fusion (N) showed osteosclerosis and deformities of femur head. Sagittal PET (O), CT (P), and PET/CT fusion (Q) of spine showed bone marrow infiltration. Axial PET (R), CT (S), and PET/CT fusion (T) of pelvis showed osteosclerosis and intense uptake of ¹⁸F-FDG. CT, computed tomography; FDG, fluorodeoxyglucose; PET, positron emission tomography.

Figure 2 Al¹⁸F-FAPI-04 PET/CT of the same patient performed 1 month after ¹⁸F-FDG PET/CT. Maximum intensity projection (A) showed uptake of Al¹⁸F-FAPI-04 in multiple bones. The bones involved in Al¹⁸F-FAPI-04 PET/CT were almost the same as in ¹⁸F-FDG PET/CT, while intensity and extent of uptake were different in these two examinations. This may indicate diverse underlying pathological process at different disease sites. Axial PET (B), CT (C), and PET/CT fusion (D) of humeral head showed cortical bone thinning, dilation of bone marrow cavity and moderate uptake of Al¹⁸F-FAPI-04 in bone marrow (arrows). Coronal PET (E), CT (F), and PET/CT fusion (G) of femur and tibia showed osteosclerosis which exhibited slight Al¹⁸F-FAPI-04 uptake. Axial PET (H), CT (I), and PET/CT fusion (J) showed osteosclerosis and deformities of femur head. Sagittal PET (K), CT (L), and PET/CT fusion (M) of spine showed bone marrow infiltration. Axial PET (N), CT (O), and PET/CT fusion (P) of pelvis showed osteosclerosis and slight uptake of Al¹⁸F-FAPI-04. CT, computed tomography; FAPI, fibroblast activation protein inhibitor; FDG, fluorodeoxyglucose; PET, positron emission tomography.

Gaucher disease influences mineralized components as well as bone marrow, and the manifestation is complex even in a single patient (5). While genetic testing and decreased glucocerebrosidase remains the cornerstone for definitive diagnosis of Gaucher disease, ¹⁸F-FDG and Al¹⁸F-FAPI-04 PET/CT offer unique and complementary clinical utilities that extend beyond what genetic testing and glucocerebrosidase test alone can provide. First of all, genetic testing and glucocerebrosidase confirms the diagnosis but cannot determine which organs/tissues are currently affected or the severity of involvement. Besides, the combination of ¹⁸F-FDG and Al¹⁸F-FAPI-04 PET/CT help distinguish different disease stages. Apart from this, Gaucher disease could not always be diagnosed timely due to the low incidence of the disease. The tracer uptake patterns in PET/CT would help doctors to recognize Gaucher disease and arrange test for definitive diagnosis.

Skeletal involvement is common and often causes pain and disability (6-8). Currently, bone manifestations are usually evaluated with MRI and X-rays (3,9,10). Although MRI and X-rays could provide structural details, they lack functional data about disease activity. In contrast, ¹⁸F-FDG PET/CT and Al¹⁸F-FAPI-04 PET/CT enable early detection before structural damage appears on MRI/X-rays. Besides, PET/CT has advantage in whole-body burden assessment and guiding interventions. This case demonstrated the value of Al¹⁸F-FAPI-04 PET/CT and ¹⁸F-FDG PET/CT in evaluation of Gaucher disease, which may be used in diagnosis, disease burden evaluation, and biopsy guidance in patients with Gaucher disease. Al¹⁸F-FAPI-04 PET/CT indicates the activation of fibroblast activation protein, and is related to fibrosis. ¹⁸F-FDG PET/CT indicates the severity of inflammation and is sensitive to early bone marrow involvement. ¹⁸F-FDG PET/CT could be used to guide biopsy toward metabolically active regions. Discrepancies between FDG and FAPI uptake may reflect disease stage differences. FDG-high/FAPI-low lesions may benefit from anti-inflammatory therapy, while FAPI-high regions might require interventions for fibrosis.

Acknowledgments

None.

Footnote

Funding: This work was supported by the National High Level Hospital Clinical Research Funding (No. 2025-PUMCH-D-003) and Peking Union Medical College Hospital Talent Cultivation Program Category D (No. UHB12835).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-999/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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