Biological Evaluation of a Fluorescent-Imaging Agent for Medullary Thyroid Cancer in an Orthotopic Model

J Clin Endocrinol Metab. 2017 Sep 1;102(9):3268-3277. doi: 10.1210/jc.2017-00573.

Abstract

Context: The primary and definitive treatment of medullary thyroid cancer (MTC) is surgical resection. Recurrent or residual disease is typically a result of incomplete surgical removal.

Objective: Our objective is to develop a compound that assists in intraoperative visualization of cancer, which would have the potential to improve surgical cure rates and outcomes.

Results: We report the biological characterization of Compound-17, which is labeled with IRdye800, allowing fluorescent visualization of MTC mouse models. We found that the agent has high affinity for two human MTC cell lines (TT and MZ-CRC1) in vitro and in vivo. We further tested the affinity of the compound in a newly developed MTC orthotopic xenograft model and found that Compound-17 produces fluorescent signals within MTC-derived orthotopic xenografts in comparison with a sequence-jumbled control compound and surrounding normal tissues.

Conclusions: Compound-17 is a unique and effective molecule for MTC identification that may have therapeutic potential.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Biopsy, Needle
  • Calcitonin / blood
  • Carcinoma, Neuroendocrine / diagnostic imaging*
  • Carcinoma, Neuroendocrine / pathology
  • Carcinoma, Neuroendocrine / surgery*
  • Disease Models, Animal
  • Fluorescent Antibody Technique / methods
  • Heterografts
  • Humans
  • Immunohistochemistry
  • Iohexol / analogs & derivatives*
  • Iohexol / pharmacology
  • Mice
  • Monitoring, Intraoperative / methods
  • Positron-Emission Tomography / methods*
  • Sensitivity and Specificity
  • Thyroid Neoplasms / diagnostic imaging
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / surgery*
  • Thyroidectomy / methods*

Substances

  • compound 17
  • Iohexol
  • Calcitonin

Supplementary concepts

  • Thyroid cancer, medullary