Targeting Amyloids with [¹⁸F]AV-45 for Medullary Thyroid Carcinoma Positron Emission Tomography/Computed Tomography...

Medullary thyroid carcinoma (MTC) is a malignant neuroendocrine tumor with a high recurrence rate. Amyloid plaques formed from the misfolding of calcitonin are the key characteristics of MTC. Herein, we conducted a first-in-human pilot clinical study by applying a β-amyloid-specific radiotracer, [¹⁸F]AV-45, to positron emission tomography (PET)/computed tomography (CT) imaging of MTC. The presence of amyloid plaques in the tumor tissue sections from five MTC patients was confirmed by hematoxylin and eosin (H&E) and Congo Red staining. [¹⁸F]AV-45 selectively accumulated in the amyloid plaques in the continued tumor tissue sections with similar distribution patterns to the H&E and Congo Red staining. In addition, the [¹⁸F]AV-45 uptake can be largely blocked by its nonradioactive reference compound. The [¹⁸F]AV-45 accumulation in the thyroid, neck lymph nodes, and muscles in healthy human subjects is close to the background indicated by PET/CT imaging. In the comparison PET/CT imaging study of a recurrent MTC patient, 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) showed an elevated uptake by multiple neck lymph nodes. In contrast, only one of these neck lymph nodes had increased [¹⁸F]AV-45 uptake. Postoperative histopathological analysis confirmed the [¹⁸F]AV-45 PET-positive lymph node as MTC with amyloid deposition, while other [¹⁸F]FDG positive lymph nodes were free from MTC and amyloid plaques. Thus, [¹⁸F]AV-45 showed the promise for the clinical PET/CT imaging of MTC.