Oncogenic Osteomalacia: Exact Tumor Localization by Co-Registration of Positron Emission and Computed Tomography

Abstract

In oncogenic osteomalacia, the causative tumor is almost always difficult to find. A novel diagnostic approach is presented that facilitates a precise and rapid localization of the associated lesion by PET-CT co-registration using the radiotracer (68)Ga-DOTANOC. Oncogenic osteomalacia (OOM) is an uncommon disorder characterized by hyperphosphaturia, hypophosphatemia, decreased vitamin D(3) serum levels, and osteomalacia. The paraneoplastic syndrome is exclusively driven by a small somatostatin receptor (sst)-positive tumor that produces phosphatonins, proteins that cause renal phosphate loss. OOM can be cured completely on tumor removal. However, the exact tumor localization is the most challenging step, because the lesion is notoriously difficult to detect by common imaging techniques. A 60-year-old woman complained of severe pain in her back and chest wall, muscle weakness, and reduced physical activity for >1 year. She suffered a metatarsal fracture and presented with hyperphosphaturia and hypophosphatemia. OOM was suspected, and a meticulous search for the tumor was initiated by conventional imaging techniques, sst-mediated imaging using (111)In-octreotide scintigraphy, and (68)Ga-DOTANOC-based positron emission tomography (PET)-CT co-registration. (68)Ga-DOTANOC is a novel radiopharmaceutical compound in which the somatostatin analog octreotide is modified at position 3, chelated with DOTA, and complexed with (68)Gallium. (68)Ga-DOTANOC has an improved affinity to sst2 and sst5 relative to other radiopeptides. Whereas common imaging techniques such as CT failed to localize the tumor, (111)In-octreotide scintigraphy was able to detect the lesion, but only PET-CT using (68)Ga-DOTANOC revealed the exact tumor localization in the right femoral head. On tumor resection, the well being of the patient improved significantly, and biochemical parameters returned to normal. (68)Ga-DOTANOC-based PET-CT is a novel and powerful approach to detect sst-positive tumors in a timely manner and to provide highly resolved images facilitating the development of a therapeutic strategy.