CXCR4-targeted PET/CT with Al18F-NOTA-Pentixather shows superior sensitivity to 18F-FDG in thyroid follicular lymphoma.

Primary thyroid follicular lymphoma (FL) is exceedingly rare with frequently low fluorine-18-fluorodeoxyglucose (18F-FDG) avidity, challenging accurate staging. We report the case of a 49-year-old female who underwent left thyroid lobectomy for a thyroid imaging reporting and data system (TI-RADS) 4a nodule, with histopathology confirming low-grade FL. Postoperative 18F-FDG positron emission tomography/computed tomography (PET/CT) showed only mild uptake at the surgical bed and cervical lymph nodes, interpreted as reactive change. A subsequent aluminum fluoride-18-1,4,7-triazacyclononane-1,4,7-triacetic acid-Pentixather (Al18F-NOTA-Pentixather) C-X-C chemokine receptor type 4 (CXCR4)-targeted PET/CT, however, revealed multiple intensely avid cervical and abdominal nodal lesions and spleen involvement. This imaging discrepancy underscores the limitations of 18F-FDG in low-grade lymphomas and suggests that CXCR4-targeted PET/CT may offer a more accurate reflection of disease burden, with potential implications for staging and therapeutic management.