Targeted tumor therapies of receptor tyrosine kinases (RTK) do not work for every patient with cancer, owing to differences in the level of RTK heterogeneity, RTK co-activation mechanisms, and other aspects of disease biology. Over the last years, the combination of non-invasive positron emission tomography (PET) with non-pharmacological doses of an RTK-specific antibody has shown the ability to study cancer biology in real-time and in the whole body of living subjects at the early stages of the disease and in response to therapies. Many RTK-specific antibody-PET imaging conjugates exist in the clinics and show potential for earlier diagnosis and accurate management of oncology patients. Herein, our review concisely focuses on clinical and preclinical data of RTK-targeted PET imaging to detect two significant biological mechanisms of tumor resistance — RTK heterogeneity and RTK co-activation. This mini-review provides an overview of RTK-targeted PET imaging studies of the last 4 years and gives collective information on how it may assist prognostic information and image disease recurrence.