Immunomedics, a biopharmaceutical company focused on developing monoclonal antibodies to treat cancer and other diseases, has reported that pre-targeting with a bispecific antibody (bsMAb) and a peptide labeled with gallium-68 (Ga-68), a PET sensitive radioisotope, produced excellent images in a human colorectal cancer model, at the Society of the Nuclear Medicine (SNM) meeting held in New Orleans, June 14-18.
The bsMAb used in the study was TF2, an antibody constructed using Immunomedics’ proprietary protein engineering platform technology, called dock-and-lock, according to the Morris Plains, N.J.-based company. TF2 specifically targets the carcinoembryonic (CEA) antigen expressed in many human cancers, and the histamine-succinyl-glycine (HSG) peptide, which in this study was labeled with Ga-68 for PET imaging.
Mice bearing human colorectal cancer transplants were pre-targeted with 0.1-10 nmol of the DNL-construct and 16 hours later injected intravenously with 10 – 100 pmol of the HSG peptide, Immunomedics said. The researchers studied four bsMAb to peptide ratios, 10:1; 25:1; 50:1; and 100:1.
High specific uptake of TF2 in the tumor was obtained at doses up to 2.5 nmol, while blood levels were sufficiently low, according to the company. At a molar TF2 to HSG ratio of 25:1, maximal accumulation of the labeled peptide in the tumor was observed. Under the optimal conditions, the researchers found that the ratios of radioisotope uptake for tumor-to-blood and tumor-to-kidney were 590 and 6, respectively. The very high ratios produced PET images of the tumor within one hour of Ga-68 injection.
"We are pleased with these preclinical results, which demonstrated that pre-targeting with bispecific antibodies can be successfully applied to the imaging of cancer," said Cynthia L. Sullivan, president and CEO of Immunomedics. Pre-targeting with bi-specific antibodies is a technology developed by IBC Pharmaceuticals, a majority owned subsidiary of Immunomedics.