Targeting Amyloids with [18F]AV-45 for Medullary Thyroid Carcinoma Positron Emission Tomography/Computed Tomography Imaging: A Pilot Clinical Study

Mol Pharm. 2022 Feb 7;19(2):584-591. doi: 10.1021/acs.molpharmaceut.1c00680. Epub 2022 Jan 4.

Abstract

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.

Keywords: PET/CT; [18F]AV-45; amyloid; medullary thyroid carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fluorodeoxyglucose F18
  • Humans
  • Neoplasm Recurrence, Local
  • Positron Emission Tomography Computed Tomography*
  • Positron-Emission Tomography / methods
  • Thyroid Neoplasms* / diagnostic imaging
  • Thyroid Neoplasms* / pathology
  • Thyroid Neoplasms* / surgery

Substances

  • Fluorodeoxyglucose F18