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

Kara K, Rossfeld, Steven E, Justiniano, Haiming, Ding, Li, Gong, Shankaran, Kothandaraman, Dwitiya, Sawant, Motoyasu, Saji, Chadwick L, Wright, Lawrence S, Kirschner, Matthew D, Ringel, Michael F, Tweedle, John E, Phay

The Journal of clinical endocrinology and metabolism |

Context: The primary and definitive treatment of medullary thyroid cancer (MTC) is surgical re- section. 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:Wereport the biological characterization ofCompound-17, which is labeled with IRdye800, allowing fluorescent visualization ofMTC mouse models.Wefound that the agent has high affinity for two humanMTCcell 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 forMTCidentification that may have therapeutic potential.