One Tracer, Whole Syndrome: CAIX-Targeted PET Unmasks the Multisystem Tumor Landscape of Von Hippel-Lindau Disease

Von Hippel-Lindau (VHL) is hereditary syndrome characterized with benign and malignant neoplasms resulting from dysregulation of hypoxia-sensitive pathway. Fifty-year-old man with VHL underwent multimodal imaging for remaining CNS disease. ⁶⁸Ga-DOTATATE PET/CT showed single cerebellar lesion, while ¹⁸F-FDG PET/CT remained negative despite active disease; [⁶⁸Ga]Ga-DPI-4452 CAIX-targeted PET/CT revealed multisystem tumor burden; cerebellar and spinal hemangioblastomas, recurrent and contralateral ccRCC lesions and epididymal involvement. This case demonstrates the ability of CAIX-targeted imaging to visualize the pervasive hypoxia-induced phenotype underlying VHL-associated neoplasms, detect biologically active but metabolically latent disease, and may represent promising molecular imaging approach for phenotype-focused evaluation of inherited tumor syndromes.