Researchers at Memorial Sloan Kettering Cancer Center in New York City and Massachusetts Institute of Technology in Boston have developed a new, three-step system that uses nuclear medicine to target and eliminate colorectal cancer. Using a mouse model, researchers achieved a 100-percent cure rate without any treatment-related toxic effects (J Nucl Med 2017;58(11):1735).

Until now, radioimmunotherapy of solid tumors using antibody-targeted radionuclides has had limited therapeutic success. "This research is novel because of the benchmarks reached by the treatment regimen, in terms of curative tumor doses, with non-toxic secondary radiation to the body's normal tissues," explained Steven M. Larson, MD, and Sarah Cheal, PhD. "The success in murine tumor models comes from the unique quality of the reagents developed by our group, and the reduction to practice methodology, including a theranostic approach that can be readily transferred, we believe, to patients."

In this study, the glycoprotein A33 (GPA33), an antigen found on over 95 percent of primary and metastatic human colorectal cancers, was targeted with a bispecific antibody for A33 tumor antigen and a second antibody for a small-molecule radioactive hapten, a complex of lutetium-177 (177Lu) and S-2-(4-aminobenzyl)1,4,7,10-tetraazacyclododecane tetra-acetic acid (177Lu-DOTA-Bn).

The DOTA-pretargeted radioimmunotherapy (PRIT) strategy was tested on a mouse model. In randomly selected mice undergoing treatment, serial SPECT/CT imaging was used to monitor treatment response and calculate radiation-absorbed doses to tumors. All the DOTA-PRIT-treated animals tolerated the treatment well, and all nine assessed mice had no trace of cancer remaining upon microscopic examination. There was also no detectable radiation damage to critical organs, including bone marrow and kidneys. The 100-percent cure rate in the mouse model suggests that anti-GPA33-DOTA-PRIT will be a potent radioimmunotherapy regimen for GPA33-positive colorectal cancer tumors in humans.