The
clinical value of current and future nanomedicines can be improved
by introducing patient selection strategies based on noninvasive sensitive
whole-body imaging techniques such as positron emission tomography
(PET). Thus, a broad method to radiolabel and track preformed nanomedicines
such as liposomal drugs with PET radionuclides will have a wide impact
in nanomedicine. Here, we introduce a simple and efficient PET radiolabeling
method that exploits the metal-chelating properties of certain drugs
(e.g., bisphosphonates such as alendronate and anthracyclines
such as doxorubicin) and widely used ionophores to achieve excellent
radiolabeling yields, purities, and stabilities with 89Zr, 52Mn, and 64Cu, and without the requirement
of modification of the nanomedicine components. In a model of metastatic
breast cancer, we demonstrate that this technique allows quantification
of the biodistribution of a radiolabeled stealth liposomal nanomedicine
containing alendronate that shows high uptake in primary tumors and
metastatic organs. The versatility, efficiency, simplicity, and GMP
compatibility of this method may enable submicrodosing imaging studies
of liposomal nanomedicines containing chelating drugs in humans and
may have clinical impact by facilitating the introduction of image-guided
therapeutic strategies in current and future nanomedicine clinical
studies.