Soft tissue musculoskeletal sarcoma (STS) is a rare and varied class of mesenchymal-derived malignancies. Due to its histopathological heterogeneity and presence in different body locations, its diagnosis and treatment continue to present a significant medical challenge. In nuclear medicine, 18F-FDG PET/CT (FDG PET/CT) has been used to grade sarcomas, predict their prognosis, and assess therapy response. Although prostate-specific membrane antigen (PSMA) has been mainly used to detect prostate cancer metastases with PSMA PET/CT imaging and treat with 225Ac/177Lu-PSMA, this antigen has been shown to accumulate in non-prostatic tissues, including several types of sarcomas.

Evaluate the potential of PSMA PET/CT in diagnosing different types of STSs compared to FDG PET/CT, with the aim of expanding the clinical management of these patients and the potential of a Theranostics strategy with radiolabeled PSMA.

Forty-four participants (20 females) with STS were prospectively enrolled and submitted to FDG PET/CT and PSMA PET/CT for primary staging, with a 48-hour interval between studies. SUVmax values were obtained in both studies of the primary STS lesion, locoregional lymph node metastases (LRLNs), distant lymph node metastases (DLNs), and bone metastases. SUVmax values among FDG PET/CT and PSMA PET/CT studies were normalized using the mediastinum SUVmax as a standard reference. The number of metastases detected by FDG PET/CT and PSMA PET/CT were also compared, as well as the absolute SUVmax values.

The absolute SUVmax values were higher on PSMA PET/CT compared to FDG PET/CT, respectively for the primary STS lesions (18.5 vs 12.8), for LRLNs (8.0 vs 4.5) and bone metastases (8.7 vs 3.2), while these values were similar for DLNs (3.0 vs 4.0). When the SUVmax values were normalized using the mediastinum as a reference the ratio comparing PSMA PET/CT to FDG PET/CT showed, respectively: 10.3 vs 5.3 for the primary STS; 4.7 vs 2.0 for LRLNs; 4.8 vs 2.9 for bone metastases; and 1.7 vs 1.7 for DLNs. PSMA PET/CT detected more LRLNs compared to FDG PET/CT (10 patients vs 7 patients, respectively) and more bone metastases (5 patients vs 3 patients). The detectability of DLNs was equal in both studies (7 patients).

Our preliminary findings indicate that PSMA PET/CT is a potential diagnostic tool for staging sarcomas patients. Due to the high uptake in the primary STS lesions and metastases, there is a potential for a theranostics approach. This study received financial support from the São Paulo State Foundation for Teaching and Research Support (Cancer Theranostics Innovation Center, (CancerThera), CEPID FAPESP #2021/10265-8).