Pretargeted immunoPET with Immunomedics' TF2 and gallium-68 (68Ga)-labeled peptide is a sensitive imaging method for colon cancer and is more specific than FDG PET, according to results presented at the annual meeting of the American Association for Cancer Research (AACR) last week in Orlando, Fla.
The objective of the preclinical study was to determine the feasibility and specificity of pretargeted immunoPET detection of colon cancer with TF2 and a small peptide labeled with 68Ga. TF2 is a bispecific antibody that specifically targets the carcinoembryonic antigen (CEA or CEACAM5) expressed in many human cancers, including colorectal cancer. Unlike conventional antibodies that can only attach to one receptor, TF2 has been modified to contain an additional binding site that recognizes a radioisotope-carrying peptide, according to Immunomedics.
Mice with a subcutaneous CEA-positive tumor on the right hind leg and an inflammation in the left thigh muscle were used by Rafke Schoffelen, MD, of Radboud University in Nijmegen, the Netherlands. Pretargeted immunoPET was also compared to FDG PET for detection of intraperitoneal CEA-expressing human colonic tumor xenografts in nude mice.
One hour after the injection of the peptide or FDG, PET/CT images were acquired. One day later, the same procedure was performed in reverse, and after microPET imaging the uptake of the 68Ga or 18F in dissected tissue was determined by the researchers.
Within one hour of injecting the 68Ga-labeled peptide, a pretargeted immunoPET scan revealed a rapid and very specific uptake of radioactivity in the tumor, while the inflamed muscle was not visualized. As a result, high tumor-to-background ratios of radioactivity concentrations (e.g. tumor/intestines ratio of 57.5) were obtained, according to Schoffelen and colleagues. In contrast, 18F-FDG localized efficiently in the tumors as well as in the inflamed muscle and in a number of normal tissues, resulting in a tumor to intestines ratio of 4.
The researchers also observed efficient tumor uptake of the 68Ga-labeled peptide in the intraperitoneal CEA-positive tumors. The high and specific uptake in the CEA-expressing tumors combined with the very low uptake in normal tissues, such as the intestines, produced clear visualization of very small abdominal tumors of less than 2 mm, noted the researchers.