PET/CT with prostate-specific membrane antigen (PSMA) has been investigated in various scenarios beyond prostate cancer, with PSMA expression reported in multiple solid tumor tissues, including their neovascular endothelium.[1] We present the case of a patient with esophageal cancer who developed brain metastasis, emphasizing the critical role of 18 F-PSMA PET/CT imaging in detecting metastatic lesions and its potential impact on guiding treatment strategies.

G. H. B., a 71-year-old Brazilian male with a history of smoking, alcohol consumption and gastroesophageal reflux disease, was diagnosed with esophagogastric adenocarcinoma in 2024. 18 F-FDG PET/CT staging revealed a localized neoplasm at the esophagogastric junction (6.4 cm, SUV=15.1) and regional paratracheal lymphadenopathy (SUV = 17.2), with no evidence of distant metastasis. The patient initiated neoadjuvant chemotherapy with the FLOT regimen (fluorouracil, leucovorin, oxaliplatin, and docetaxel) and after four cycles, he underwent 18 F-FDG and 18 F-PSMA PET/CT. 18 F-FDG PET/CT revealed disease progression with increased primary lesion metabolic activity, new paratracheal lymphadenopathy and a right temporal lobe lesion consistent with metastasis. In comparison, 18 F-PSMA PET/CT showed higher 18 F-PSMA uptake in the temporal lobe lesion, similar uptake in the distal esophagus, and reduced uptake in the mediastinal lymph nodes. The multidisciplinar team contraindicated esophagectomy, recommending radiotherapy for the central nervous system metastasis over neurosurgery, and palliative systemic treatment.

To our knowledge, this is the first reported case of brain metastasis from esophageal cancer identified using 18 F-PSMA PET/CT. The increased 18 F-PSMA uptake in the brain lesion, compared to 18 F-FDG PET/CT, may be attributed to PSMA overexpression in the neovascular endothelium of non-prostate cancers.[2] 18 F-PSMA PET/CT represents a novel diagnostic tool for non-prostate cancers, potentially offering higher sensitivity for detecting brain metastases than 18 F-FDG PET/CT. Further clinical trials are warranted to investigate its role in gastrointestinal malignancies.