Dual-Tracer PET/CT Pinpoints Rare Tumor Behind Severe Bone Pain

A 25-year-old man whose year-long, progressively worsening bone pain had been mistaken for spondyloarthritis and severe osteoporosis finally received the right diagnosis thanks to a two-tracer imaging strategy: ⁶⁸Ga-DOTATATE PET/CT lit up a small tumor in his mandible that ¹⁸F-FDG PET/CT had shown only dimly. The case, published as an open-access case report in EJNMMI Reports in August 2026, describes how molecular imaging identified a phosphaturic mesenchymal tumor—the cause of his tumor-induced osteomalacia—and how surgery reversed his metabolic disease within days.

Tumor-induced osteomalacia is a paraneoplastic syndrome in which a tumor, usually a tiny and slow-growing mesenchymal one, drives kidney wasting of phosphate. The culprit tumors secrete fibroblast growth factor-23, a hormone that inhibits renal phosphate reabsorption. Localization is the critical step: finding the lesion makes curative resection possible.

In the reported case, the young man arrived with progressive generalized joint pain, fatigue, and a 15-kilogram weight loss over the course of a year. His initial workup pointed to spondyloarthritis, severe osteoporosis, and femoral head necrosis, and symptomatic treatment brought little relief. Laboratory tests told a different, more telling story: severe hypophosphatemia at 0.45 millimoles per liter against a normal range of 0.81 to 1.45, hypocalcemia, an elevated alkaline phosphatase of 520 units per liter, and a normal parathyroid hormone level. That biochemical signature—phosphate wasting without parathyroid overactivity—is the classic fingerprint of tumor-induced osteomalacia.

Whole-body bone scintigraphy added anatomical breadth to the picture, showing multifocal tracer uptake in the ribs, pelvis, large joints, and mandible, a pattern consistent with metabolic bone disease rather than a single orthopedic problem. The next step was a pair of positron emission tomography scans, each built around a different molecular target, performed to hunt down the lesion secreting the phosphate-wasting hormone.

The first scan, ¹⁸F-FDG PET/CT, the workhorse glucose-metabolism tracer of oncology, revealed an osteolytic lesion in the left mandible with moderate uptake, quantified as a maximum standardized uptake value of 5.2. The lesion was visible, but its metabolic signal was muted—bright enough to flag, not bright enough to stand out from the many benign and malignant bone tumors that can show moderate FDG avidity. In oncology at large, FDG PET is everywhere; for phosphaturic mesenchymal tumors, the authors note, its sensitivity is variable.

The second scan told a far more decisive story. ⁶⁸Ga-DOTATATE PET/CT, which binds to somatostatin receptors overexpressed on the surface of these tumors, demonstrated intense tracer uptake at exactly the same mandibular site, with a maximum standardized uptake value of 18.7—more than three times the FDG signal. No other suspicious lesions appeared anywhere in the body. Taken together with the biochemical findings, the imaging team strongly suspected a phosphaturic mesenchymal tumor of the mandible as the source of the patient’s osteomalacia.

Surgical resection of the mandibular mass confirmed the suspicion. Histopathology revealed a spindle cell tumor with chondroid matrix differentiation. Immunohistochemistry showed positivity for vimentin, focal positivity for SATB2, and negativity for S-100, an immunophenotype consistent with a phosphaturic mesenchymal tumor. The diagnostic chain—biochemistry, dual-tracer imaging, and pathology—closed cleanly. The clinical payoff was swift: serum phosphate normalized within 15 days of the operation, and the patient’s bone pain subsided significantly.

The case illustrates a clinical paradigm the authors spell out explicitly: when tumor-induced osteomalacia is confirmed biochemically but conventional imaging with CT or MRI fails to localize the culprit—which happens often, especially when the tumor sits in an atypical location—⁶⁸Ga-DOTATATE PET/CT should be considered the imaging modality of choice. Somatostatin receptor subtype 2 is overexpressed on these tumors, giving the somatostatin-targeted tracer a molecular handle that glucose imaging lacks. The authors argue that this precision not only localizes the tumor but also aids surgical planning, and they note that recent studies suggest a theranostic potential for somatostatin-targeted radioligands in cases that are unresectable or metastatic, extending the same molecular target from diagnosis toward treatment.

Enthusiasm needs tempering, and the authors themselves supply the caveats. This is a single case report; the rarity of phosphaturic mesenchymal tumors means that no head-to-head tracer comparison trials exist to settle the question of sensitivity in a rigorous way. Notably, serum fibroblast growth factor-23 was not measured in this patient, because the assay was not clinically available at the institution at the time of diagnosis. The authors acknowledge that although FGF-23 is a key biomarker for tumor-induced osteomalacia, its measurement is not considered mandatory for diagnosis when the clinical, biochemical, imaging, and histopathological findings all point the same way—but its absence remains a limitation of the report.

With those limits in mind, the takeaway is procedural rather than revolutionary. Diffuse bone pain combined with unexplained hypophosphatemia should trigger a search for a phosphate-wasting tumor, and when conventional imaging comes up empty, somatostatin-receptor PET offers a targeted, high-signal hunt that in this case converted a year of misdirected treatment into a localized lesion, a successful resection, and a normalized blood phosphate level within two weeks. For patients with this rare disease, the difference between a vague rheumatologic label and a curable tumor can come down to which radiotracer is injected first.

Subject of Research: Using dual-tracer ¹⁸F-FDG and ⁶⁸Ga-DOTATATE PET/CT to localize a phosphaturic mesenchymal tumor causing tumor-induced osteomalacia

Article Title: Precise localization of phosphaturic mesenchymal tumor causing tumor-induced osteomalacia: the value of dual-tracer imaging with ¹⁸F-FDG and ⁶⁸Ga-DOTATATE PET/CT

Article References: Ye, T., Wen, X., & Wang, R. (2026). Precise localization of phosphaturic mesenchymal tumor causing tumor-induced osteomalacia: the value of dual-tracer imaging with ¹⁸F-FDG and ⁶⁸Ga-DOTATATE PET/CT. EJNMMI Reports, 10(1), Article 30. https://doi.org/10.1186/s41824-026-00299-3

Image Credits: AI Generated

DOI: 10.1186/s41824-026-00299-3

Keywords: tumor-induced osteomalacia, phosphaturic mesenchymal tumor, 68Ga-DOTATATE PET/CT, 18F-FDG PET/CT, FGF-23, hypophosphatemia, somatostatin receptor imaging, mandibular tumor, molecular imaging, case report, bone pain, nuclear medicine