Credit: Thomas Günther et al.
Researchers have made a breakthrough in the effective identification of medullary thyroid cancer (MTC) through the development of a novel PET imaging agent. Results indicate the PET imaging agent could prove to be a promising theranostic candidate in clinical applications.
One of the rarest forms of thyroid cancer, MTC accounts for around three percent of all thyroid cancer cases. Due to its origination from different cells than that of most thyroid cancers, unique imaging and therapy targets are necessary for effective treatment.
“The cholecystokinin-2 receptor (CCK-2R) is overexpressed on most MTC cells and various compounds targeting CCK-2R have been developed over the past several years. Most of these compounds, however, have low metabolic stability, which is not ideal for radioligand therapy,” said Thomas Günther, pharmaceutical radiochemist at Stanford University, California. “With a simplistic design modification to tackle instability issues, our team created multiple theranostic agents and sought to evaluate their effectiveness.”
In the study, published in the Journal of Nuclear Medicine, three compounds (DOTA-CCK-66, DOTA-CCK 66.2, and DOTA-MGS5 external reference) were separately labeled and the CCK-2R affinity of each compound on MTC cells was analyzed. After further analyses of the compound's stability, biodistribution, imaging, and competition on CCK-2R expressing tumors in mice 68Ga-DOTA-CCK-66 was selected based on its overall performance in these tests.
Further testing with 68Ga-DOTA-CCK-66 on two MTC patients showed favorable biodistribution, high accumulation of activity in tumors, and was well tolerated by the patients.
“Due to increased in vivo stability, our compound reveals favorable tumor uptake as well as an improved activity clearance from off-target tissues. This could result in enhanced lesion detection in PET imaging and additionally enable targeted MTC radioligand therapy,” said Constantin Lapa, MD, director of nuclear medicine at University Hospital Augsburg.