Advances and challenges in immunoPET methodology

Immuno-positron emission tomography (immunoPET) enables imaging of specific targets that play a role in targeted therapy and immunotherapy, such as antigens on cell membranes, targets in the disease microenvironment or immune cells. The most common immunoPET applications use a monoclonal antibody labeled with a relatively long-lived positron emitter such as 89Zr (T1/2= 78.4 h), but also smaller antibody-based constructs labeled with various other positron emitting radionuclides are being investigated. Thereby, this molecular imaging technique can guide the development of new drugs and may have a pivotal role in selecting patients for a particular therapy. In early phase immunoPET trials, multiple imaging time points are used to examine the time-dependent biodistribution and to determine the optimal imaging time point, which may be several days after tracer injection due to the slow kinetics of larger molecules. Once this has been established, usually only one static scan is performed and semi-quantitative values are reported. However, total PET uptake of a tracer is the sum of specific and nonspecific uptake. In addition, uptake may be affected by other factors such as perfusion, pre-/co-administration of the unlabeled molecule, and the treatment schedule. This article reviews imaging methodology used in immunoPET studies and is divided in two parts. The first part summarizes the vast majority of clinical immunoPET studies applying semi-quantitative methodology. The second part focuses on a handful of studies applying pharmacokinetic models and includes preclinical and simulation studies. Finally, the potential and challenges in immunoPET quantification methodology are discussed within the context of the recent technological advancements provided by long axial field of view PET/CT scanners.