Preclinical Imaging in Targeted Cancer Therapies

Preclinical imaging with radiolabeled probes can provide noninvasive tools to test the efficacy of targeted agents in tumors harboring specific genetic alterations and to identify imaging parameters that can be used as pharmacodynamics markers in cancer patients. The present review will primarily focus on preclinical imaging studies that can accelerate the clinical approval of targeted agents and promote the development of imaging biomarkers for clinical applications. Since only subgroups of patients may benefit from treatment with targeted anticancer agents, the identification of a patient population expressing the target is of primary importance for the success of clinical trials. Preclinical imaging studies tested the ability of new radiolabeled compounds to recognize mutant, amplified, or overexpressed targets and some of these tracers were transferred to the clinical setting. More common tracers such as F-18-Fluorothymidine and F-18-Fluorodeoxyglucose were employed in animal models to test the inhibition of the target and downstream pathways through the evaluation of early changes of proliferation and glucose metabolism allowing the identification of sensitive and resistant tumors. Furthermore, since the majority of patients treated with targeted anticancer agents will invariably develop resistance, preclinical imaging studies were performed to test the efficacy of reversal agents to overcome resistance. These studies provided consistent evidence that imaging with radiolabeled probes can monitor the reversal of drug resistance by newly designed alternative compounds. Finally, despite many difficulties and challenges, preclinical imaging studies targeting the expression of immune checkpoints proved the principle that it is feasible to select patients for immunotherapy based on imaging findings. In conclusion, preclinical imaging can be considered as an integral part of the complex translational process that moves a newly developed targeted agent from laboratory to clinical application intervening in all clinically relevant steps including patient selection, early monitoring of drug effects and reversal of drug resistance. (C) 2019 Elsevier Inc. All rights reserved.