Nuclear medicine could show complete cure in colorectal cancer

Hematology- Oncology

To target and eliminate colorectal cancer, a novel three-step system was developed by researchers using nuclear medicine. In this study, researchers achieved a 100% cure rate without any treatment-related toxic effects in a mouse model.

Novel three-step pre-targeted radioimmunotherapy offers safe, effective treatment and there are no treatment-related toxic effects. Steven M and Sarah Cheal researchers of the study explained, "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," until now, antibody-targeted radionuclides had limited therapeutic success in radioimmunotherapy of solid tumors.

They continued, "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." Single agents that used to both diagnose and treat disease, known as a theranostic agent.

This agent first finds the cancer cells, then destroys them, (leaving healthy cells unharmed) minimizing side effects and improving quality of life for patients.

An antigen called the glycoprotein A33 (GPA33), found on over 95 percent of primary and metastatic human colorectal cancers, in this study. Bispecific antibody targeted for A33 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).

In a mouse model, DOTA-pre-targeted radioimmunotherapy (PRIT) strategy was tested. A serial single-photon emission computed tomography/computed topography (SPECT/CT) imaging was used to monitor treatment response and calculate radiation-absorbed doses to tumors, in a randomly selected mouse. All animals treated with DOTA-PRIT tolerated the treatment well, and there is no trace of cancer remaining upon microscopic examination in all 9 assessed mice. Detectable radiation damage to critical organs, including bone marrow and kidneys were not seen.

The study suggests that anti-GPA33-DOTA-PRIT will be a potent radioimmunotherapy regimen for GPA33-positive colorectal cancer tumors in humans since preliminarily mouse model showed 100% cure rate results.

Colorectal cancer is the third most common cancer affecting both men and women, according to Centers for Disease Control and Prevention. The uses of this nuclear medicine treatment protocol could extend to other cancers as well.

"If clinically successful, our approach will expand the repertoire of effective treatments for oncologic patients. The system is designed as a 'plug and play' system, which allows for the use of many fine antibodies targeting human tumor antigens and is applicable, in principle, to virtually all solid and liquid tumors in man." researchers mentioned, "There is a huge unmet need in oncology, especially for the solid tumors, for curative treatments for advanced disease. This includes colon, breast, pancreas, melanoma, lung, and oesophagal, to name a few," Larson and Cheal stated.