Novel immuno-PET agent seeks cancer vasculature

An investigational immune-PET biomarker maps tumor vasculature while skipping healthy tissues, according to a study published Feb. 13 in the Journal of Nuclear Medicine.

Tumor endothelial marker 1 (TEM1/endosialin) is a tumor vascular marker (TMV) that is very strongly expressed in a range of cancer types and relatively mute in normal tissues. A novel monoclonal antibody called MORAb-004 has been developed to dock with TEM1 and give away the presence cancerous tumors.

Researchers including Ann-Marie Chacko, PhD, from the division of nuclear medicine and clinical molecular imaging in the department of radiology, Perelman School of Medicine at the University of Pennsylvania in Philadelphia, evaluated both I-124 and I-125 MORAb-004 for their effectiveness as a tracer for tumor vasculature and specifically TEM1 with a preclinical PET system. Results of the study showed high binding capability of I-124 MORAb-004 in relation to extracellular epitope of human TEM1.

“Targeting tumor vasculature rather than tumor cells themselves has several advantages,” wrote Chacko et al. “Among these, tumor vasculature expresses unique molecular targets that are absent in normal vasculature, vascular targets are less likely to be lost due to adaptation or mutations, and TVMs are readily accessible to blood circulation. Consequently, TVMs are attractive targets for antibody-based cancer diagnosis of molecular phenotype and personalized therapy."

The researchers were able to achieve “excellent” image contrast with I-124 MORAb-004 and uptake of the agent was substantially increased in tumors expressing TEM1 compared to controls, which showed no binding.

Both radiolabeled immune-PET agents demonstrated 90 percent immunoreactivity. Fast and “highly specific and sensitive” uptake of MORAb-004 was seen in mice bearing MSI-TEM1 tumors at approximately four hours with about a 153 percentage injected dose per gram, about 127.1 at 24 hours, approximately 130.3 at 48 hours, 160.9 at 72 hours and 10.7 at about six days following injection. Binding specificity was also observed by researchers who conducted blocking studies with extra non-labeled MORAb-004.

“In our preclinical model, with hTEM1 exclusively expressed on engineered murine endothelial cells that integrate into the tumor vasculature, I-124 MORAb-004 displays high tumor–to–background tissue contrast for detection of hTEM1 in easily accessible tumor vascular compartments,” wrote the authors.

This research presents I-124 MORAb-004 as a potentially beneficial immune-PET agent for the evaluation of TEM1-positive cancers. Further research is needed to validate these results in clinical trials.