Initial clinical evaluation of iodine-125-labeled chimeric 17-1A for metastatic colon cancer

The internalizing properties of murine antibody 17-1A in human colon cancer cells make it attractive as a carrier for radionuclides with short range emissions such as 125I. Murine 17-1A IgG2a antibody, which reacts against human gastrointestinal cancers, has been chimerized by joining its variable region with human IgG1 k constant region. A pilot clinical trial of increasing doses of 125I-chimeric 17-1A in patients with metastatic colorectal cancer has been conducted.

Patients were treated in groups of 2-4; 2 patients at Hahnemann University and 26 at the University of Alabama at Birmingham. Groups 1-5 received single administrations with 125I doses of 20, 40, 60, 80 or 100 mCi. Subsequent groups received therapeutic doses of 150, 200 or 250 mCi, with the dose subdivided into infusing of 50 or 100 mCi at 4-day intervals. All treatments were delivered in an outpatient setting using radiation precautions. Labeling at 10 mCi/mg antibody was performed on the day of treatment.

Pharmocokinetics of circulating antibody was studied for initial patients, showing alpha T 1/2 of 17-27 hr and beta T 1/2 of 100-190 hr. Whole-body T 1/2 of radioactivity was determined by measuring urinary excretion or gamma emissions. Treatment was well tolerated without significant acute or late side effects. No significant bone marrow suppression or other dose-limiting toxicities were noted over this dose range. No objective responses were noted.

These results show that high-dose outpatient radioimmunotherapy with an 125I-labeled internalizing antibody can be achieved without significant patient toxicity or radiation hazard.