Pretargeted Immuno-PET: Overcoming Limitations of Space and Time.

Although the development of radiolabeled antibodies for preclinical and clinical use in PET imaging continues to mature into a widespread technique (1–4), limitations still remain: namely space, in which the antigens to which our antibody is targeting are located (intracellularly or cell surface, bound or circulating), and time, the extended period after which the imaging must take place, to allow for blood clearance of the long-circulating antibody. Typically, circulating antigens can be overcome by a predose of cold antibody to saturate these off-target sites, whereas limitations in timing can be overcome by simply imaging at longer time points. The widespread availability of long-lived radionuclides in the field of nuclear medicine such as 89Zr and 124I have enabled the latter. However, the main drawback in direct imaging of radiolabeled antibodies with such radionuclides is that the patient is exposed to radiation longer than traditional radionuclides, resulting in greater amounts of accumulated absorbed dose to normal tissues.