As one of the most biocompatible and well-tolerated inorganic nanomaterials,
silica-based nanoparticles (SiNPs) have received extensive attention over the last several decades. Recently, positron emission tomography (PET) imaging of radiolabeled SiNPs has provided a highly sensitive, noninvasive, and quantitative readout of the organ/tissue distribution, pharmacokinetics, and
tumor targeting efficiency in vivo, which can greatly expedite the clinical translation of these promising NPs. Encouraged by the successful PET imaging of patients with metastatic
melanoma using 124I-labeled ultrasmall SiNPs (known as Cornell dots or C dots) and their approval as an
Investigational New Drug (IND) by the United States Food and Drug Administration, different
radioisotopes (64Cu, 89Zr, 18F, 68Ga, 124I, etc.) have been reported to radiolabel a wide variety of SiNPs-based nanostructures, including dense
silica (dSiO2), mesoporous
silica (MSN), biodegradable mesoporous
silica (bMSN), and hollow mesoporous
silica nanoparticles (
HMSN). With in-depth knowledge of coordination chemistry, abundant
silanol groups (-Si-O-) on the
silica surface or inside mesoporous channels not only can be directly used for
chelator-free radiolabeling but also can be readily modified with the right
chelators for
chelator-based labeling. However, integrating these labeling strategies for constructing stably radiolabeled SiNPs with high efficiency has proven difficult because of the complexity of the involved key parameters, such as the choice of
radioisotopes and
chelators, nanostructures, and radiolabeling strategy. In this Account, we present an overview of recent progress in the development of radiolabeled SiNPs for
cancer theranostics in the hope of speeding up their biomedical applications and potential translation into the clinic. We first introduce the basic principles and mechanisms for radiolabeling SiNPs via coordination chemistry, including general rules of selecting proper
radioisotopes, engineering
silica nanoplatforms (e.g., dSiO2, MSN,
HMSN) accordingly, and chelation strategies for enhanced labeling efficiency and stability, on which our group has focused over the past decade. Generally, the medical applications guide the choice of specific SiNPs for radiolabeling by considering the inherent functionality of SiNPs. The
radioisotopes can then be determined according to the amenability of the particular SiNPs for
chelator-based or
chelator-free radiolabeling to obtain high labeling stability in vivo, which is a prerequisite for PET to truly reflect the behavior of SiNPs since PET imaging detects the
isotopes rather than nanoparticles. Next, we highlight several recent representative biomedical applications of radiolabeled SiNPs including molecular imaging to detect specific lesions, PET-guided
drug delivery, SiNP-based
theranostic cancer agents, and clinical studies. Finally, the challenges and prospects of radiolabeled SiNPs are briefly discussed toward clinical
cancer research. We hope that this Account will clarify the recent progress on the radiolabeling of SiNPs for specific medical applications and generate broad interest in integrating nanotechnology and PET imaging. With several ongoing clinical trials, radiolabeled SiNPs offer great potential for future patient stratification and
cancer management in clinical settings.