[Development of ADCs Using Molecular Imaging]

Abstract

Antibody-drug conjugates (ADCs) comprise an antibody, a linker, and a drug or payload. The selection of a tumor-specific antibody and development of a linker having an efficient controlled drug release (CDR) are critical steps in developing a fully functional and effective ADC. In our research strategy, molecular imaging technologies have been employed to evaluate the efficiency of antibody delivery and CDR of the linker. In preclinical setting, antibody delivery into the tumor area or antibody penetration through the tumor stroma in malignant lymphoma or pancreatic tumor was evaluated by in vivo fluorescence imaging technique. Positron emission tomography (PET) imaging studies were conducted using ⁸⁹Zr-labeled antibody to evaluate tumor targeting in a spontaneous carcinogenesis model. The model had dense stroma and was pathophysiologically very similar to human cancer. The drug imaging system, using microscopic mass spectroscopy (MMS) with enhanced resolution and sensitivity, was used for the evaluation of CDR. Paclitaxel (PTX)-incorporated micelle, a high-molecular-weight (HMW) carrier with CDR, showing similar properties as those of ADC, was analyzed. In contrast to free PTX, micelle selectively increased drug accumulation into the tumor and reduced toxicity in normal tissues by the enhanced permeability and retention (EPR) effect. Our drug imaging system has been used recently to evaluate the CDR of the ADC-linker. We present our work on the development of ADC using a molecular imaging technique.

Keywords: MS imaging; antibody; antibody-drug conjugate; drug delivery system; molecular imaging.