Overexpression and/or mutations of the receptor tyrosine kinase (RTK) subfamilies, such as epidermal growth factor receptors (EGFR) and vascular endothelial growth factor receptors (VEGFR), are closely associated with tumor cell growth, differentiation, proliferation, apoptosis, and cellular invasiveness. Monoclonal antibodies (mAb) and tyrosine kinase inhibitors (TKI) specifically inhibiting these RTKs have shown remarkable success in improving patient survival in many cancer types. However, poor response and even drug resistance inevitably occur. In this setting, the ability to detect and visualize RTKs with noninvasive diagnostic tools will greatly refine clinical treatment strategies for cancer patients, facilitate precise response prediction, and improve drug development. Positron emission tomography (PET) agents using targeted radioactively labeled antibodies have been developed to visualize tumor RTKs and are changing clinical decisions for certain cancer types. In the present review, we primarily focus on PET imaging of RTKs using radiolabeled antibodies with an emphasis on the clinical applications of these immunoPET probes. (C) 2018 AACR.

The rapidly evolving field of cancer immunotherapy recently saw the approval of several new therapeutic antibodies. Several cell therapies, for example, chimeric antigen receptor-expressing T cells (CAR-T), are currently in clinical trials for a variety of cancers and other diseases. However, approaches to monitor changes in the immune status of tumors or to predict therapeutic responses are limited. Monitoring lymphocytes from whole blood or biopsies does not provide dynamic and spatial information about T cells in heterogeneous tumors. Positron emission tomography (PET) imaging using probes specific for T cells can noninvasively monitor systemic and intratumoral immune alterations during experimental therapies and may have an important and expanding value in the clinic.

The rapidly evolving field of cancer immunotherapy recently saw the approval of several new therapeutic antibodies. Several cell therapies, for example, chimeric antigen receptor-expressing T cells (CAR-T), are currently in clinical trials for a variety of cancers and other diseases. However, approaches to monitor changes in the immune status of tumors or to predict therapeutic responses are limited. Monitoring lymphocytes from whole blood or biopsies does not provide dynamic and spatial information about T cells in heterogeneous tumors. Positron emission tomography (PET) imaging using probes specific for T cells can noninvasively monitor systemic and intratumoral immune alterations during experimental therapies and may have an important and expanding value in the clinic.

Amino acid-based tracers have been extensively investigated for positron emission tomography (PET) imaging of brain tumors, and C-11-methionine (C-11-MET) is one of the most extensively investigated. However, widespread clinical use of C-11-MET is challenging due to the short half-life of C-11 and low radiolabeling yield. In this issue of the European Journal of Nuclear Medicine and Molecular Imaging, Yang and colleagues report an F-18-labeled boron-derived methionine analog, F-18-B-MET, as a potential substitute for C-11-MET in PET imaging of glioma. The push-button synthesis, highly efficient radiolabeling, and good imaging performance in glioma models make this tracer a promising candidate for future clinical translation.

The importance of medical imaging in the diagnosis and monitoring of cancer cannot be overstated. As personalized cancer treatments are gaining popularity, a need for more advanced imaging techniques has grown significantly. Nanoparticles are uniquely suited to fill this void, not only as imaging contrast agents but also as companion diagnostics. This review provides an overview of many ways nanoparticle imaging agents have contributed to cancer imaging, both preclinically and in the clinic, as well as charting future directions in companion diagnostics. We conclude that, while nanoparticle-based imaging agents are not without considerable scientific and developmental challenges, they enable enhanced imaging in nearly every modality, hold potential as in vivo companion diagnostics, and offer precise cancer treatment and maximize intervention efficacy.

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 I-124-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 (Cu-64, Zr-89, F-18, Ga-68, I-124, etc.) have been reported to radiolabel a wide variety of SiNPs-based nanostructures, including dense silica (dSiO(2)), mesoporous silica (MSN), biodegradable mesoporous silica (bMSN), and hollow mesoporous silica nano-particles (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., dSiO(2), 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.

Amino acid-based tracers have been extensively investigated for positron emission tomography (PET) imaging of brain tumors, and C-11-methionine (C-11-MET) is one of the most extensively investigated. However, widespread clinical use of C-11-MET is challenging due to the short half-life of C-11 and low radiolabeling yield. In this issue of the European Journal of Nuclear Medicine and Molecular Imaging, Yang and colleagues report an F-18-labeled boron-derived methionine analog, F-18-B-MET, as a potential substitute for C-11-MET in PET imaging of glioma. The push-button synthesis, highly efficient radiolabeling, and good imaging performance in glioma models make this tracer a promising candidate for future clinical translation.

The importance of medical imaging in the diagnosis and monitoring of cancer cannot be overstated. As personalized cancer treatments are gaining popularity, a need for more advanced imaging techniques has grown significantly. Nanoparticles are uniquely suited to fill this void, not only as imaging contrast agents but also as companion diagnostics. This review provides an overview of many ways nanoparticle imaging agents have contributed to cancer imaging, both preclinically and in the clinic, as well as charting future directions in companion diagnostics. We conclude that, while nanoparticle-based imaging agents are not without considerable scientific and developmental challenges, they enable enhanced imaging in nearly every modality, hold potential as in vivo companion diagnostics, and offer precise cancer treatment and maximize intervention efficacy.