Molecular imaging techniques for protein therapeutics rely on reporter labels, especially radionuclides or sometimes near-infrared fluorescent moieties, which must be introduced with minimal perturbation of the protein's function in vivo and are detected non-invasively during whole-body imaging. PET is the most sensitive whole-body imaging technique available, making it possible to perform biodistribution studies in humans with as little as 1 mg of injected antibody carrying 1 mCi (37 MBq) of zirconium-89 radiolabel. Different labeling chemistries facilitate a variety of optical and radionuclide methods that offer complementary information from microscopy and autoradiography and offer some trade-offs in whole-body imaging between cost and logistic difficulty and image quality and sensitivity (how much protein needs to be injected). Interpretation of tissue uptake requires consideration of label that has been catabolized and possibly residualized. Image contrast depends as much on background signal as it does on tissue uptake, and so the choice of injected dose and scan timing guides the selection of a suitable label and helps to optimize image quality. Although only recently developed, zirconium-89 PET techniques allow for the most quantitative tomographic imaging at millimeter resolution in small animals and they translate very well into clinical use as exemplified by studies of radiolabeled antibodies, including trastuzumab in breast cancer patients, in The Netherlands.