Single photon emission computed tomography/computed tomography clue to pulmonary metastasis in osteosarcoma: a diagnostic pitfall of technetium-99m methylene diphosphonate uptake

Introduction

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents (1), frequently arising in the metaphyseal regions of long bones and exhibiting early metastatic potential, particularly to the lungs (2,3). Although pulmonary metastases are common (4), reports describing their detection via technetium-99m methylene diphosphonate (^99mTc-MDP) single photon emission computed tomography/computed tomography (SPECT/CT) remain limited. Given its osteogenic nature, OS often produces osteoblastic metastases, enabling visualization on ^99mTc-MDP bone scans, even within soft tissue sites (5,6). Compared with planar imaging, SPECT/CT offers superior anatomical localization and can detect early-stage metastases not yet demonstrating overt osteoid formation, thereby enhancing diagnostic accuracy.

This study, through analyzing a case of a 15-year-old female patient with pulmonary metastasis of OS, not only deepens our understanding of OS and expands the application scope of SPECT/CT, but also provides valuable experience for the diagnosis and treatment of such diseases.

Case presentation

A 15-year-old girl presented with a 3-month history of right knee pain. Needle biopsy of a lesion in the right proximal tibia confirmed conventional OS (Ki-67 labeling index: ~40%). To evaluate the extent of disease and guide treatment planning, a whole-body bone scintigraphy using ^99mTc-MDP was performed. The scan revealed intense radiotracer uptake in the right knee, corresponding to the primary tumor. Additionally, an unexpected focus of increased uptake was noted in the posterior left eighth rib region on planar imaging (Figure 1, black arrow), raising the possibility of skeletal metastasis. However, SPECT/CT localized the lesion to the lower lobe of the left lung (Figure 2A, yellow arrows), excluding osseous involvement. Another pulmonary nodule without MDP uptake was also identified (Figure 2B, yellow arrowheads). These findings suggested pulmonary metastases. The patient subsequently received one cycle of neoadjuvant chemotherapy with methotrexate and cisplatin, followed by two cycles of adjuvant chemotherapy with adriamycin and ifosfamide. Wide excision of the right tibial tumor was performed, followed by resection of the pulmonary nodules at an outside institution. Pathological analysis confirmed both lung lesions as OS metastases. At 2-year follow-up, repeat whole-body bone scintigraphy demonstrated reduced tracer activity in the right knee, consistent with postoperative changes, and no abnormal extraskeletal MDP uptake elsewhere (Figure 3, anterior and posterior views). The patient remains in good general condition and is under routine surveillance.

Figure 1 The ^99mTc-MDP whole-body bone scan indicated intense radiotracer uptake in the right knee and in the posterior region of the left eighth rib on planar imaging (black arrow). ^99mTc-MDP, technetium-99m methylene diphosphonate.

Figure 2 Axial CT, SPECT, and SPECT/CT fusion after ^99mTc-MDP administration. (A) SPECT/CT localized the lesion to the lower lobe of the left lung (yellow arrows). (B) SPECT/CT identified another pulmonary nodule without MDP uptake (yellow arrowheads). CT, computed tomography; SPECT, single photon emission computed tomography; ^99mTc-MDP, technetium-99m methylene diphosphonate.

Figure 3 Two years later, repeat whole-body bone scintigraphy showed no abnormal extraskeletal uptake of MDP (anterior and posterior views). MDP, methylene diphosphonate.

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 Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient’s parents 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.

Discussion

OS is a highly malignant disease prone to lung metastasis (7). The poor prognosis of OS patients is closely related to the development of lung metastasis, which is almost the cause of death for all OS patients (8). Therefore, early detection of pulmonary metastases is critical for timely management and improved survival outcomes. Clinically, both whole-body bone scintigraphy and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/CT (PET/CT) are routinely used for staging. While FDG PET/CT plays a major role in systemic evaluation, bone scintigraphy remains more sensitive for detecting osteogenic metastases.

As shown in this case, whole-body bone scan is more sensitive to osteogenic metastases, and the unexpected tracer uptake in the lung was initially ambiguous on planar imaging. However, SPECT/CT precisely localized it to the pulmonary parenchyma, excluding rib involvement and prompting further clinical intervention. This case highlights the important clinical value of SPECT/CT in characterizing indeterminate extraosseous MDP-avid foci detected on routine bone scintigraphy in OS patients. Such non-specific uptake can indicate osteoblastic metastases, but differentiation based on planar imaging alone is often difficult due to limited spatial resolution. The fusion of anatomical and functional data provided by SPECT/CT enables precise lesion localization and objective characterization of potential extraosseous osteogenic foci. This enhances early detection of occult metastases and supports more accurate clinical decision-making. Consistent with previous findings (9), this case confirms the irreplaceable role of SPECT/CT in improving lesion localization and diagnostic confidence. Notably, SPECT/CT also revealed an additional pulmonary metastasis that showed no MDP uptake on planar scintigraphy, emphasizing its superior sensitivity and the added value of multimodal imaging integration in comprehensive disease evaluation.

Extraosseous uptake of ^99mTc-MDP has been reported in various conditions, including primary malignancies (10), osseous metastases (5,11), amyloidosis (12), and iatrogenic microembolism (13). This phenomenon may be influenced by factors such as extracellular fluid expansion, increased vascular permeability, and elevated local calcium concentration (14). In both benign and malignant tumors, MDP accumulation is generally associated with soft tissue calcification, hyperemia, or both. Therefore, when encountering extraosseous MDP uptake in clinical practice, a comprehensive differential diagnosis should be considered, including neoplastic lesions (e.g., OS metastasis) and non-neoplastic causes such as post-traumatic callus formation. Careful integration of imaging findings with the patient’s medical history, laboratory results, and clinical presentation is essential to accurately determine the etiology and avoid diagnostic pitfalls. In the present case, pulmonary metastases from OS demonstrated focal MDP uptake, likely due to tumor-induced calcification within the lung parenchyma. This underscores the importance of recognizing abnormal extraosseous tracer uptake as a potential indicator of metastatic disease and reinforces the utility of bone scintigraphy in the comprehensive evaluation of osteogenic tumors. The findings in this case offer valuable insights for clinical interpretation and highlight the expanded diagnostic capabilities of whole-body bone imaging in pediatric oncology.

Conclusions

In conclusion, this study, through the analysis of a case of pulmonary metastasis from OS, confirms the irreplaceable sensitivity of SPECT/CT in precisely localizing lesions, enhancing diagnostic confidence, and detecting occult metastatic lesions. It also highlights the value of multimodal imaging integration for comprehensive assessment of osteogenic tumors.

Acknowledgments

None.

Footnote

Funding: This research was supported by Hubei Provincial Natural Science Foundation Project (No. 2024AFB633).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1937/coif). X.X. reports that this research was supported by Hubei Provincial Natural Science Foundation Project (No. 2024AFB633). The other 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 Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient’s parents 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/.

References

1. Cersosimo F, Lonardi S, Bernardini G, Telfer B, Mandelli GE, Santucci A, Vermi W, Giurisato E. Tumor-Associated Macrophages in Osteosarcoma: From Mechanisms to Therapy. Int J Mol Sci 2020;21:5207. [Crossref] [PubMed]
2. Sadoughi F, Maleki Dana P, Asemi Z, Yousefi B. DNA damage response and repair in osteosarcoma: Defects, regulation and therapeutic implications. DNA Repair (Amst) 2021;102:103105. [Crossref] [PubMed]
3. Raymond AK, Jaffe N. Osteosarcoma multidisciplinary approach to the management from the pathologist's perspective. Cancer Treat Res 2009;152:63-84. [Crossref] [PubMed]
4. Chiesa AM, Spinnato P, Miceli M, Facchini G. Radiologic Assessment of Osteosarcoma Lung Metastases: State of the Art and Recent Advances. Cells 2021;10:553. [Crossref] [PubMed]
5. Shen C. Peritoneal Metastasis of Osteosarcoma in 99m Tc-MDP SPECT/CT Imaging. Clin Nucl Med 2024;49:e587-8. [Crossref] [PubMed]
6. Subedi U, Mahdi RA, Mittal BR, Singh H, Kumar R, Bachhal V. Solitary Peritoneal Metastasis in Case of Osteosarcoma Detected by FDG PET/CT. Clin Nucl Med 2025;50:e62-3. [Crossref] [PubMed]
7. Liu S, Tang H, Li S, Guan J, Cai Y, Li H, Yan W, Dai W, Xiao D, Zou Z, Feng W, Zhan X, Liu Y, He J. Single-Cell RNA Sequencing Reveals the Critical Role of SEC16B in Lung Metastasis of Osteosarcoma. FASEB Bioadv 2025;7:e70025. [Crossref] [PubMed]
8. Reinecke JB, Jimenez Garcia L, Saraf AJ, Hinckley J, Gross AC, Le Pommellet H, Gutpell KM, Cam M, Cannon MV, Gust MJ, Vatelle S, Gryder BE, Dries R, Roberts RD. Metastasis-Initiating Osteosarcoma Subpopulations Establish Paracrine Interactions with Lung and Tumor Cells to Create a Metastatic Niche. Cancer Res 2025;85:4341-58. [Crossref] [PubMed]
9. Mebarki M, Medjahedi A, Menemani A, Betterki S, Terki S, Berber N. Osteosarcoma pulmonary metastasis mimicking abnormal skeletal uptake in bone scan: utility of SPECT/CT. Clin Nucl Med 2013;38:e392-4. [Crossref] [PubMed]
10. Zhang L, He Q, Zhou T, Zhang B, Li W, Peng H, Zhong X, Ma L, Zhang R. Accurate characterization of (99m)Tc-MDP uptake in extraosseous neoplasm mimicking bone metastasis on whole-body bone scan: contribution of SPECT/CT. BMC Med Imaging 2019;19:44. [Crossref] [PubMed]
11. Huang W, Zhou Y, Yang Q, Li L, Kang L. Extraosseous Uptake and Multiple Metastases of Splenic Composite Hemangioendothelioma on 99m Tc-MDP Scintigraphy. Clin Nucl Med 2023;48:1107-10. [Crossref] [PubMed]
12. Agarwal KK, Karunanithi S, Roy SG, Bal C, Kumar R. 99mTc-MDP SPECT/CT demonstrating extraosseous periarticular amyloid deposits in primary systemic amyloidosis associated with multiple myeloma. Clin Nucl Med 2015;40:189-90. [Crossref] [PubMed]
13. Lei L, Deng Y, Ding H, Zhang W. Iatrogenic Lung Microembolism Resulted in Extraosseous Uptake of 99mTc-MDP. Clin Nucl Med 2020;45:871-2. [Crossref] [PubMed]
14. Peller PJ, Ho VB, Kransdorf MJ. Extraosseous Tc-99m MDP uptake: a pathophysiologic approach. Radiographics 1993;13:715-34. [Crossref] [PubMed]