Ultrasmall Porous Silica Nanoparticles with Enhanced Pharmacokinetics for Cancer Theranostics.

Theranostic nanoparticles hold the potential to greatly improve cancer management by providing personalized medicine. Although many theranostic nanoconstructs have been successful in preclinical studies, clinical translation is still hampered by their limited targeting capability and lack of successful therapeutic efficacy. We report the use of novel ultrasmall porous silica nanoparticles (UPSN) with enhanced pharmacokinetics such as high target tissue accumulation (12% ID/g in the tumor) and evasion from the reticuloendothelial system (RES) organs.

CD38-Targeted Theranostics of Lymphoma with Zr/Lu-Labeled Daratumumab.

Lymphoma is a heterogeneous disease with varying clinical manifestations and outcomes. Many subtypes of lymphoma, such as Burkitt's lymphoma and diffuse large B cell lymphoma, are highly aggressive with dismal prognosis even after conventional chemotherapy and radiotherapy. As such, exploring specific biomarkers for lymphoma is of high clinical significance.

In vivo characterization of PD-L1 expression in breast cancer by immuno-PET with Zr-labeled avelumab.

Programmed death protein 1 and programmed death-ligand 1 (PD-1/PD-L1) have been widely studied as one of the most critical immune check-point pairs in the cancer microenvironment. In breast cancer (BrCa), the expression of PD-L1 is regarded as a determinant biomarker for patient stratification and prediction of inhibition response. Quantitative positron emission tomography (PET) imaging of PD-L1 expression in tumors using a therapeutic antibody in the clinic seems to be a promising approach that can complement conventional histopathological methods and overcome several issues, such as the tumor heterogeneities, sampling representativeness and clear differentiation of positive and negative results.

Y-Labeled Monoclonal Antibody Targeting Tissue Factor for Pancreatic Cancer Theranostics.

Pancreatic cancer is highly aggressive, with a median survival time of less than 6 months and a 5-year overall survival rate of around 7%. The poor prognosis of PaCa is largely due to its advanced stage at diagnosis and the lack of efficient therapeutic options. Thus, the development of an efficient, multifunctional PaCa theranostic system is urgently needed.

A Melanin-Based Natural Antioxidant Defense Nanosystem for Theranostic Application in Acute Kidney Injury.

Acute kidney injury (AKI) is frequently associated with oxidative stress and causes high mortality annually in clinics. Nanotechnology-mediated antioxidative therapy is emerging as a novel strategy for the treatment of AKI. Herein, a novel biomedical use of the endogenous biopolymer melanin as a theranostic natural antioxidant defense nanoplatform for AKI is reported.

ImmunoPET imaging of CD38 expression in hepatocellular carcinoma using Cu-labeled daratumumab.

CD38 is expressed on the surface of many immune cells, which are closely associated with antitumor immunity and immune tolerance of tumor cells. Therefore, monitoring CD38 expression has gained great attention for tracking the progression of tumors and cancer treatment. Herein, we aim to develop a PET tracer using an anti-CD38 monoclonal antibody (daratumumab) to monitor CD38 expression in hepatocellular carcinoma (HCC).

Intrathecal Administration of Nanoclusters for Protecting Neurons against Oxidative Stress in Cerebral Ischemia/Reperfusion Injury.

Oxidative stress is one of the important mechanisms in cerebral ischemia/reperfusion (I/R) injury. Antioxidants with high brain accumulation are highly desired to help prevent cerebral I/R injury. Herein, intrathecal injection of polyoxometalate (POM) nanoclusters as nano-antioxidants with preferential brain uptake were applied for neuronal protection in cerebral I/R injury.

Aptamer-Conjugated Framework Nucleic Acids for the Repair of Cerebral Ischemia-Reperfusion Injury.

Effective therapy for protecting dying neurons against cerebral ischemia-reperfusion injury (IRI) represents a substantial challenge in the treatment of ischemic strokes. Oxidative stress coupled with excessive inflammation is the main culprit for brain IRI that results in neuronal damage and disability. Specifically, complement component 5a (C5a) exacerbates the vicious cycle between oxidative stress and inflammatory responses.

Dual-labeled pertuzumab for multimodality image-guided ovarian tumor resection.

Pertuzumab is clinically employed in the treatment of cancers over-expressing human epidermal growth factor receptor 2 (HER2). Herein, we developed dual-labeled pertuzumab with a radionuclide (Zr) and a near-infrared fluorophore (IRDye 800CW) to investigate the feasibility of utilizing dual-labeled monoclonal antibodies (mAbs) with numerous imaging modalities for preoperative imaging and image-guided surgery in ovarian cancer models. MAbs were dually-labeled with Zr and IRDye 800CW to generate Zr-Df-pertuzumab-800CW or Zr-Df-IgG-800CW.

Molecular imaging of β-cells: diabetes and beyond.

Since diabetes is becoming a global epidemic, there is a great need to develop early β-cell specific diagnostic techniques for this disorder. There are two types of diabetes (i.e.

CD146-Targeted Multimodal Image-Guided Photoimmunotherapy of Melanoma.

For melanoma resistant to molecularly targeted therapy and immunotherapy, new treatment strategies are urgently needed. A molecularly targeted theranostic pair may thus be of importance, where the diagnostic probe facilitates patient stratification and the therapeutic companion treats the selected cases. For this purpose, flow cytometry is used to assess the CD146 level in melanoma cells.

Noninvasive Imaging and Quantification of Radiotherapy-Induced PD-L1 Upregulation with Zr-Df-Atezolizumab.

Immune checkpoint expression is highly dynamic, and combination treatments including radiotherapy can particularly modulate this expression. PET imaging using Zr-Df-atezolizumab can provide insight into the levels of PD-L1 variation following radiotherapy treatments. In vitro screening was used to monitor PD-L1 expression by lung cancer cells following radiotherapy.

Site-Specific Immuno-PET Tracer to Image PD-L1.

The rapid ascension of immune checkpoint blockade treatments has placed an emphasis on the need for viable, robust, and noninvasive imaging methods for immune checkpoint proteins, which could be of diagnostic value. Immunoconjugate-based positron emission tomography (immuno-PET) allows for sensitive and quantitative imaging of target levels and has promising potential for the noninvasive evaluation of immune checkpoint proteins. However, the advancement of immuno-PET is currently limited by available imaging tools, which heavily rely on full-length IgGs with Fc-mediated effects and are heterogeneous mixtures upon random conjugation with chelators for imaging.

Antibody and fragment-based PET imaging of CTLA-4+ T-cells in humanized mouse models.

Imaging of immunotherapy targets using positron emission tomography (PET) can allow for noninvasive monitoring of their dynamic expression and may allow for patient stratification in the future. Therefore, two tracers targeting CTLA-4, one a full antibody and the other a F(ab') fragment, were radiolabeled with Cu and validated in humanized mouse models. Ipilimumab was digested to develop ipilimumab-F(ab'), and both the intact antibody and the fragment were conjugated with NOTA to chelate Cu for PET.

Antibody-Based Tracers for PET/SPECT Imaging of Chronic Inflammatory Diseases.

Chronic inflammatory diseases are often progressive, resulting not only in physical damage to patients but also social and economic burdens, making early diagnosis of them critical. Nuclear medicine techniques can enhance the detection of inflammation by providing functional as well as anatomical information when combined with other modalities such as magnetic resonance imaging, computed tomography or ultrasonography. Although small molecules and peptides were mainly used for the treatment and imaging of chronic inflammatory diseases in the past, antibodies and their fragments have also been emerging for chronic inflammatory diseases as they show high specificity to their targets and can have various biological half-lives depending on how they are engineered.

PET Imaging of Receptor Tyrosine Kinases in Cancer.

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.

Multimodality Imaging Agents with PET as the Fundamental Pillar.

Positron emission tomography (PET) provides quantitative information in vivo with ultra-high sensitivity but is limited by its relatively low spatial resolution. Therefore, PET has been combined with other imaging modalities, and commercial systems such as PET/computed tomography (CT) and PET/magnetic resonance (MR) have become available. Inspired by the emerging field of nanomedicine, many PET-based multimodality nanoparticle imaging agents have been developed in recent years.

Intrinsically Zirconium-89-Labeled Manganese Oxide Nanoparticles for Dual-Modality Positron Emission Tomography and Magnetic Resonance Imaging.

Manganese-based nanoparticles (NPs) have recently attracted much attention in the field of biomedical imaging due to their impressive enhanced T1 contrast ability. Although the reported manganese-based NPs have exhibited good imaging capabilities as contrast agents, it is still urgent to develop novel multifunctional manganese-based imaging probes for future biomedical imaging, especially PET/MRI probes. Herein, we present chelator-free zirconium-89 (89Zr, t1/2: 78.

Y-Based Theranostics Targeting Angiogenesis in a Murine Breast Cancer Model.

Angiogenesis is widely recognized as one of the hallmarks of cancer. Therefore, imaging and therapeutic agents targeted to angiogenic vessels may be widely applicable in many types of cancer. To this end, the theranostic isotope pair, Y and Y, were used to create a pair of agents for targeted imaging and therapy of neovasculature in murine breast cancer models using a chimeric anti-CD105 antibody, TRC105.

Noninvasive PET Imaging of T cells.

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.

Noninvasive Trafficking of Brentuximab Vedotin and PET Imaging of CD30 in Lung Cancer Murine Models.

CD30 has been considered a unique diagnostic and therapeutic target for CD30-positive lymphomas and some lung diseases. Additionally, CD30 has shown high expression in clinical lung cancer samples. In this study, Zr-radiolabeled brentuximab vedotin (BV) was developed for in vivo tracking of BV and imaging CD30 expression in lung cancer models via conjugation with desferrioxamine (Df).

Radiolabeling Silica-Based Nanoparticles via Coordination Chemistry: Basic Principles, Strategies, and Applications.

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-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, Zr, F, Ga, I, etc.

Big Potential from Small Agents: Nanoparticles for Imaging-Based Companion Diagnostics.

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.

One-step synthesis of an F-labeled boron-derived methionine analog: a substitute for C-methionine?

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