False-positive and true-positive orbital iodine-131 uptake after radioiodine therapy: two contrasting cases clarified by SPECT/CT

Introduction

Radioactive iodine [iodine-131 (¹³¹I)] therapy is the recommended treatment for ablation of thyroid remnant and metastatic lesions after surgery for differentiated thyroid cancer (DTC), significantly reducing the risk of recurrence (1). Post-treatment ¹³¹I single-photon emission computed tomography/computed tomography (SPECT/CT) whole-body imaging occasionally reveals abnormal radioactive accumulation in the ocular region (2). Abnormal orbital ¹³¹I uptake on post-treatment ¹³¹I SPECT/CT is uncommon and may indicate either benign false-positive activity or metastatic disease. Distinguishing these entities is clinically important. This paper presents two contrasting cases of DTC patients who exhibited abnormal ocular uptake after ¹³¹I therapy—one attributable to an artificial eyeball and the other to orbital metastasis from thyroid cancer. By comparing their clinical presentations and ¹³¹I uptake characteristics on SPECT/CT imaging, we highlight key distinguishing features between benign artifact and true malignant uptake, offering a practical reference for the differential diagnosis of similar rare findings.

Case presentation

A 34-year-old male previously underwent total thyroidectomy for papillary thyroid carcinoma (PTC). Pathology confirmed classic PTC with metastasis to 6 of 7 right central lymph nodes, staging as T3aN1aM0 [American Joint Committee on Cancer (AJCC) 8th Edition (3)]. According to 2025 American Thyroid Association (ATA) guidelines (4), the patient was classified as low-to-intermediate risk. Four months postoperatively, after discontinuing levothyroxine for three weeks, the patient’s stimulated thyroglobulin level was measured at 0.887 µg/L. Subsequently, he underwent ¹³¹I therapy (120 mCi), followed by a whole-body scan 3 days post-treatment.

Post-therapy ¹³¹I SPECT/CT was performed at 72 hours using a GE Discovery NM/CT 670 scanner. SPECT acquisition parameters included a 128×128 matrix, a high-energy general-purpose (HEGP) collimator, a 364 keV (±10%) energy window, 60 projections (15 sec each). CT parameters were 140 kV and 220 mA. Reconstruction utilized ordered subset expectation maximization (OSEM) with CT-based attenuation correction. Images were fused on a Xeleris workstation.

Post-treatment ¹³¹I whole-body scan revealed intense uptake in the thyroid bed region (Figure 1, blue arrowheads), suggesting residual thyroid tissue. Notably, focal ¹³¹I uptake was visible in the right eye, which necessitated dedicated SPECT/CT for localization. This abnormal uptake was localized between the orbital implant and the ocular prosthesis without structural abnormality (Figure 1, red arrows). Given the patient’s history of right enucleation with ocular prosthesis implantation following a motor vehicle accident, the abnormal uptake was attributed to the right ocular prosthesis.

Figure 1 Post-treatment ¹³¹I whole-body scan and fused SPECT/CT images reveal physiological thyroid bed uptake and focal ¹³¹I uptake in the right eye. (A,B) Anterior-posterior views of the post-treatment ¹³¹I whole-body scan. Blue arrowheads: thyroid bed uptake. Red arrows: focal uptake in the eye (ocular prosthesis). (C) Axial SPECT/CT cross-section showing ¹³¹I uptake in the right eye (red arrows). ¹³¹I, iodine-131; SPECT/CT, single-photon emission computed tomography/computed tomography.

A 52-year-old female patient presented with occasional tearing and blurred vision. A magnetic resonance imaging (MRI) at a local hospital suggested an intracranial mass lesion. She was subsequently transferred to our hospital for skull base surgery. Postoperative pathology confirmed metastatic follicular thyroid carcinoma (FTC) involving the right temporal pole, lateral orbital wall, and pterygopalatine fossa. One month later, she underwent total thyroidectomy. Pathology confirmed FTC with skeletal muscle invasion and metastasis to six supraclavicular lymph nodes, staging as T3bN1bM1 (AJCC 8th Edition) (3). According to 2025 ATA guidelines (4), this patient was classified as high-risk. One month postoperatively, after discontinuing levothyroxine for three weeks, her stimulated thyroglobulin level reached 5,733 µg/L. The patient subsequently underwent oral ¹³¹I therapy (200 mCi), followed by a whole-body scan 3 days post-treatment.

Post-therapy ¹³¹I SPECT/CT was performed at 72 hours using a GE Discovery NM/CT 670 scanner. SPECT acquisition parameters included a 128×128 matrix, an HEGP collimator, a 364 keV (±10%) energy window, 60 projections (15 sec each). CT parameters were 140 kV and 220 mA. Reconstruction utilized OSEM with CT-based attenuation correction. Images were fused on a Xeleris workstation.

Post-treatment ¹³¹I whole-body scan revealed intense uptake in the thyroid bed region (Figure 2, blue arrowheads), suggesting residual thyroid tissue. Notably, focal ¹³¹I uptake was observed in both orbital regions, prompting further cerebral SPECT/CT imaging. Cerebral SPECT/CT revealed localized uptake confined to the bilateral greater wings of the sphenoid bone and the right orbital wall, highly suggestive of bone metastases from FTC (Figure 2, red arrows). Pre-therapeutic whole-body bone imaging revealed abnormal hyperactivity in the right orbital region, mild hyperactivity along the lateral margin of the left orbital bone, and minimal hyperactivity in occipital bone (Figure 2, purple arrows).

Figure 2 Post-treatment ¹³¹I whole-body scan, SPECT/CT fusion images, and pre-treatment imaging findings: thyroid bed uptake, bilateral focal ocular ¹³¹I uptake (bone metastasis), and intracranial bone metastases. (A,B) Anterior-posterior views of post-treatment ¹³¹I whole-body scan. Blue arrowheads: thyroid bed uptake. Red arrows: focal ocular uptake (bone metastasis). (C,D) Anterior-posterior views of whole-body bone imaging. Purple arrows: bilateral orbital bone metastases. (E) Axial pre-iodine therapy cerebral MRI and axial SPECT/CT cross-section showing bilateral sphenoid wing and right orbital lateral wall ocular ¹³¹I uptake. Orange arrows: T1 enhancing destructive soft-tissue lesion, and focal ¹³¹I uptake at the right orbital posteroinferolateral wall and adjacent to right sphenoid sinus. Yellow arrows: T1 enhancing nodule and focal ¹³¹I uptake in the left temporal pole. ¹³¹I, iodine-131; MRI, magnetic resonance imaging; SPECT/CT, single-photon emission computed tomography/computed tomography; T1WI+C, T1-weighted imaging with contrast enhancement.

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 patients 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

We report two rare cases of ocular uptake identified on post-therapy whole-body iodine scans in patients with thyroid carcinoma. Although neither case is individually novel, the comparison of these two cases provides a practical framework for differential diagnosis: one patient had benign uptake attributable to an artificial eye, while the other had malignant uptake from orbital bone metastasis confirmed by pathology. Through SPECT/CT fusion imaging integrated with pathological and clinical data, these contrasting cases demonstrate how a structured differential approach can definitively distinguish benign entities from malignant pathology, thereby preventing misdirected therapy.

There are four principal categories associated with the abnormal ocular radioactive iodine uptake: (I) tumoral/functional sodium/iodide symporter (NIS)-mediated uptake, most critically metastatic disease; (II) retention-related uptake due to tear pooling or drainage obstruction; (III) inflammatory uptake from benign or postoperative conditions; and (IV) external contamination.

Distant metastases in differentiated thyroid carcinoma most commonly occur in the lungs and bones. Ocular involvement presents a rarity (2), and when observed, may indicate advanced-stage disease carrying a more aggressive clinical course (5). If whole-body ¹³¹I scan reveals radioactive concentration at an ocular metastatic lesion, it indicates that the lesion retains intact iodine metabolism pathways, including functional NIS membrane localization and sufficient organelle capacity (2). To determine whether the iodine-uptake lesion is located within the orbital wall or intraocular tissues, SPECT/CT fusion imaging is recommended to be performed. For tumoral causes, cortical bone destruction with localized uptake suggests orbital bone metastasis (6), as exemplified by our second case, in which cerebral SPECT/CT demonstrated discontinuity of the right cranial vault with an associated soft tissue mass and abnormal tracer accumulation in the bilateral greater wings of the sphenoid bone, the lateral wall of the right orbit, and the occipital bone—findings corroborated by skull base pathology. In contrast, nodular uptake involving the scleral wall or intraocular space may suggest choroidal or iris metastasis (7). If necessary, whole-body bone imaging and high-resolution MRI should be added to further confirm the burden of bone metastasis and assess involvement of the optic nerve and lens.

Benign ocular lesions can also exhibit ¹³¹I uptake, primarily through two mechanisms: retention and inflammation. Retention-related causes include nasolacrimal duct stenosis and artificial eyes, both of which can cause ¹³¹I uptake artifacts due to obstructed tear drainage and poor tear circulation likely due to retention of iodine-containing tears within the conjunctival fornix surrounding the prosthesis, respectively (8-11). Such artifacts diminish or disappear after tear duct irrigation (11). Our first case illustrated this mechanism: SPECT/CT revealed mild tracer uptake around the orbital implant and artificial eye; combined with the patient’s history of prosthesis replacement, this was considered to be physiological and benign. Clinicians should take precautions before scanning (such as early detection and irrigation) to reduce potential radiation injury to the ocular surface (11,12).

Inflammatory and cystic causes encompass several benign etiologies. Cystic lesions—both ocular (conjunctival inclusion cysts) and extrapulmonary cysts at sites such as the bronchi, kidneys, and liver—can demonstrate iodine uptake, likely due to passive tracer diffusion into cyst fluid (13-18). Inflammatory lesions include dacryocystitis and postoperative inflammatory responses (19). Walsh et al. previously reported focal iodine uptake following left supraorbital metal clip placement, attributed to postoperative inflammatory response induced by metallic foreign bodies (20).

Contamination-related causes represent the simplest but often overlooked source of false-positive ocular uptake. Contamination of the eye with ¹³¹I-containing tears, saliva, or sweat may also yield false positives, which can be distinguished by repeat scanning after simple saline irrigation (21).

Conclusions

In summary, abnormal ocular radioactive iodine uptake on post-treatment scans requires careful differential diagnosis. We have summarized the category, the cause, imaging findings, history and diagnostic confirmation of the orbital ¹³¹I uptake in Table 1. SPECT/CT provides decisive anatomical localization and enables accurate distinction between benign causes and true metastatic disease, thereby guiding appropriate management.

Acknowledgments

None.

Footnote

Funding: This study was supported by National Natural Science Foundation of China (grant No. 82102102).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2026-1-0355/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 Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patients 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. Wartofsky L, Sherman SI, Gopal J, Schlumberger M, Hay ID. The use of radioactive iodine in patients with papillary and follicular thyroid cancer. J Clin Endocrinol Metab 1998;83:4195-203. [Crossref] [PubMed]
2. Palaniswamy SS, Subramanyam P. Unusual Sites of Metastatic and Benign I 131 Uptake in Patients with Differentiated Thyroid Carcinoma. Indian J Endocrinol Metab 2018;22:740-50. [Crossref] [PubMed]
3. Perrier ND, Brierley JD, Tuttle RM. Differentiated and anaplastic thyroid carcinoma: Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin 2018;68:55-63.
4. Ringel MD, Sosa JA, Baloch Z, Bischoff L, Bloom G, Brent GA, Brock PL, Chou R, Flavell RR, Goldner W, Grubbs EG, Haymart M, Larson SM, Leung AM, Osborne JR, Ridge JA, Robinson B, Steward DL, Tufano RP, Wirth LJ. 2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer. Thyroid 2025;35:841-985. [Crossref] [PubMed]
5. Pagsisihan DA, Aguilar AH, Maningat MP. Orbital metastasis as initial manifestation of a widespread papillary thyroid microcarcinoma. BMJ Case Rep 2015; [Crossref]
6. Varadarajan VV, Pace EK, Patel V, Sawhney R, Amdur RJ, Dziegielewski PT. Follicular thyroid carcinoma metastasis to the facial skeleton: a systematic review. BMC Cancer 2017;17:225. [Crossref] [PubMed]
7. Besic N, Luznik Z. Choroidal and orbital metastases from thyroid cancer. Thyroid 2013;23:543-51. [Crossref] [PubMed]
8. Suresh A, Esposito G, Davidson B, Doroslovački P, Jonklaas J. Radioactive Iodine Treatment for Thyroid Cancer Complicated by Lacrimal Sac Retention of Iodine. JCEM Case Rep 2025;3:luae234. [Crossref] [PubMed]
9. Kim IH, Yoon JK, Lee SJ, Jeong E, An YS. A Case of Radioactive Iodine Uptake Found in Artificial Eye. Clin Nucl Med 2019;44:317-8. [Crossref] [PubMed]
10. Lee JY, Song HS, Kang M. Physiological Uptake of Radioactive Iodine Around an Artificial Eyeball Observed with Single-Photon Emission Computed Tomography/Computed Tomography After Radioactive Iodine Treatment. Nucl Med Mol Imaging 2020;54:204-6. [Crossref] [PubMed]
11. Bakheet SM, Hammami MM, Hemidan A, Powe JE, Bajaafar F. Radioiodine secretion in tears. J Nucl Med 1998;39:1452-4.
12. Ali MJ. Iodine-131 Therapy and Nasolacrimal Duct Obstructions: What We Know and What We Need to Know. Ophthalmic Plast Reconstr Surg 2016;32:243-8. [Crossref] [PubMed]
13. García-Moreno RM, Escabias C, Utrilla C, Ruiz-Bravo E, Sánchez M, Lecumberri B. Orbital Radioiodine Uptake on Scintigraphy in a Patient with Thyroid Cancer. Eur Thyroid J 2019;8:221-4. [Crossref] [PubMed]
14. Makarewicz M, Skierkowski W, Makarewicz J. Orbital Radioiodine Uptake in Epithelial Conjunctival Inclusion Cyst on Scintigraphy in a Patient With Differentiated Thyroid Cancer. Clin Nucl Med 2023;48:e382-4. [Crossref] [PubMed]
15. Jiang X, Zeng H, Gong J, Huang R. Unusual uptake of radioiodine in a retroperitoneal bronchogenic cyst in a patient with thyroid carcinoma. Clin Nucl Med 2015;40:435-6. [Crossref] [PubMed]
16. Barbaro D, Campennì A, Forleo R, Lapi P. False-positive radioiodine uptake after radioiodine treatment in differentiated thyroid cancer. Endocrine 2023;81:30-5. [Crossref] [PubMed]
17. Al-Houwari R, Moghrabi S, Abu Shattal M, Al-Ibraheem A. Hepatic Cyst Radioiodine Uptake on Whole-Body Scan in Differentiated Thyroid Cancer: Implications for Lesion Characterization and Misdiagnosis Avoidance. Cureus 2025;17:e82789. [Crossref] [PubMed]
18. Brucker-Davis F, Reynolds JC, Skarulis MC, Fraker DL, Alexander HR, Weintraub BD, Robbins J. False-positive iodine-131 whole-body scans due to cholecystitis and sebaceous cyst. J Nucl Med 1996;37:1690-3.
19. Bakheet SM, Hammami MM. False-positive radioiodine whole-body scan in thyroid cancer patients due to unrelated pathology. Clin Nucl Med 1994;19:325-9. [Crossref] [PubMed]
20. Walsh JP, Sims JB, Iranpour P. False-Positive Radioiodine Uptake From an Intracranial Surgical Clip. Clin Nucl Med 2022;47:e279-e280. [Crossref] [PubMed]
21. Ibis E, Wilson CR, Collier BD, Akansel G, Isitman AT, Yoss RG. Iodine-131 contamination from thyroid cancer patients. J Nucl Med 1992;33:2110-5.