NCT01565200.

Purpose: To provide proof of principle of safety, breast tumorspecific uptake, and positive tumor margin assessment of the systemically administered near-infrared fluorescent tracer bevacizumab-IRDye800CW targeting VEGF-A in patients with breast cancer.Experimental Design: Twenty patients with primary invasive breast cancer eligible for primary surgery received 4.5 mg bevacizumab-IRDye800CW as intravenous bolus injection. Safety aspects were assessed as well as tracer uptake and tumor delineation during surgery and ex vivo in surgical specimens using an optical imaging system. Ex vivo multiplexed histopathology analyses were performed for evaluation of biodistribution of tracer uptake and coregistration of tumor tissue and healthy tissue.

More than 50 monoclonal antibodies (mAbs), including several antibody-drug conjugates, are in advanced clinical development, forming an important part of the many molecularly targeted anticancer therapeutics currently in development. Drug development is a relatively slow and expensive process, limiting the number of drugs that can be brought into late-stage trials. Development decisions could benefit from quantitative biomarkers, enabling visualization of the tissue distribution of (potentially modified) therapeutic mAbs to confirm effective whole-body target expression, engagement, and modulation and to evaluate heterogeneity across lesions and patients. Such biomarkers may be realized with positron emission tomography imaging of radioactively labeled antibodies, a process called immunoPET. This approach could potentially increase the power and value of early trials by improving patient selection, optimizing dose and schedule, and rationalizing observed drug responses. In this review, we summarize the available literature and the status of clinical trials regarding the potential of immunoPET during early anticancer drug development.