The use of radiolabeled monoclonal antibodies (MAbs) directed against tumor-associated antigens for cancer imaging and therapy has been widely studied. However, MAbs slowly clear the from circulation and non-target tissue. In case of imaging, this causes high background signal in normal organs and for radionuclide therapy this results in high radiation exposure to healthy tissue, which may case for example myelotoxicity. Pretargeting has been developed to reduce the radiation dose to normal tissues. In this approach, a bispecific monoclonal antibody (bsMAb) is administered intravenously and given time to accumulate in the tumor and clear from the circulation. Then, a radiolabeled hapten peptide is administered that clears rapidly from the blood, but is trapped in the tumor by the anti–hapten-binding arm of the bsMAb (Figure 1).
In our group, we develop novel pretargeting strategies for cancer imaging and therapy. For example, we have shown that TF2, a bsMAb with binding to CEA and the hapten HSG, and 68Ga-labeled di-HSG-DOTA peptide IMP288, can be used to image CEA-expressing tumors. Furthermore, treatment with 177Lu- or 213Bi-IMP288 delayed the growth of CEA-positive human colonic tumors in mice and a first feasibility study with 177Lu-IMP288 has been performed in colon cancer patients. Another pretargeting strategy focuses on prostate cancer imaging and treatment, using the anti-TROP-2 bsMAb TF12. Furthermore, a dual-labeled (IRDye800CW and 111In) labeled peptide has been used for pre-operative SPECT/CT imaging, intra-operative near infrared fluorescence imaging, and image guided surgery (Figure 2).