PET radiometals for antibody labeling.

Abstract

Recent advances in molecular characterization of tumors have made possible the emergence of new types of cancer therapies where traditional cytotoxic drugs and nonspecific chemotherapy can be complemented with targeted molecular therapies. One of the main revolutionary treatments is the use of monoclonal antibodies (mAbs) that selectively target the disseminated tumor cells while sparing normal tissues. mAbs and related therapeutics can be efficiently radiolabeled with a wide range of radionuclides to facilitate preclinical and clinical studies. Non-invasive molecular imaging techniques, such as Positron Emission Tomography (PET), using radiolabeled mAbs provide useful information on the whole-body distribution of the biomolecules, which may enable patient stratification, diagnosis, selection of targeted therapies, evaluation of treatment response, and prediction of dose limiting tissue and adverse effects. In addition, when mAbs are labeled with therapeutic radionuclides, the combination of immunological and radiobiological cytotoxicity may result in enhanced treatment efficacy. The pharmacokinetic profile of antibodies demands the use of long half-life isotopes for longitudinal scrutiny of mAb biodistribution and precludes the use of well-stablished short half-life isotopes. Herein, we review the most promising PET radiometals with chemical and physical characteristics that make the appealing for mAb labeling, highlighting those with theranostic radioisotopes.