Innovations in Nuclear Medicine Imaging for Reactive Oxygen Species: Applications and Radiopharmaceuticals.

Reactive oxygen species (ROS) are generated during normal cellular energy production and play a critical role in maintaining cellular function. However, excessive ROS can damage cells and tissues, contributing to the development of diseases such as cardiovascular, inflammatory, and neurodegenerative disorders. This review explores the potential of nuclear medicine imaging techniques for detecting ROS and evaluates various radiopharmaceuticals used in these applications.

In Vivo Evaluation of Ga-Labeled NOTA-EGFRvIII Aptamer in EGFRvIII-Positive Glioblastoma Xenografted Model.

EGFRvIII is expressed only in tumor cells and strongly in glioblastoma and is considered a promising target in cancer diagnosis and therapy. Aptamers are synthetic single-stranded oligonucleotides that bind to biochemical target molecules with high binding affinity and specificity. This study examined the potential of the Ga-NOTA-EGFRvIII aptamer as a nuclear imaging probe for visualizing EGFRvIII-expressing glioblastoma by positron emission tomography (PET).

Radiopharmaceuticals for Skeletal Muscle PET Imaging.

The skeletal muscles account for approximately 40% of the body weight and are crucial in movement, nutrient absorption, and energy metabolism. Muscle loss and decline in function cause a decrease in the quality of life of patients and the elderly, leading to complications that require early diagnosis. Positron emission tomography/computed tomography (PET/CT) offers non-invasive, high-resolution visualization of tissues.

Development of PET Radioisotope Copper-64-Labeled Theranostic Immunoliposomes for EGFR Overexpressing Cancer-Targeted Therapy and Imaging.

Combining standard surgical procedures with personalized chemotherapy and the continuous monitoring of cancer progression is necessary for effective NSCLC treatment. In this study, we developed liposomal nanoparticles as theranostic agents capable of simultaneous therapy for and imaging of target cancer cells. Copper-64 (Cu), with a clinically practical half-life ( = 12.

Saengmaeksan, a traditional polyherbal formulation containing Panax ginseng, improves energy metabolism during exercise.

Saengmaeksan (SMS), a representative oriental medicine that contains Panax ginseng Meyer, Liriope muscari, and Schisandra chinensis (1:2:1), is used to improve body vitality and enhance physical activity. However, there is limited scientific evidence to validate the benefits of SMS. Here, we investigated the in vitro and in vivo regulatory effects of SMS and its constituents on energy metabolism and the underlying molecular mechanisms.

In vivo tissue pharmacokinetics of ERBB2-specific binding oligonucleotide-based drugs by PET imaging.

Although aptamers have shown excellent target specificity in preclinical and clinical studies either by themselves or as aptamer-drug conjugates, their in vivo tissue pharmacokinetic (PK) analysis is still problematic. We aimed to examine the utility of image-based positron emission tomography (PET) to evaluate in vivo tissue PK, target specificity, and applicability of oligonucleotides. For this, fluorine-18-labeled aptamers with erb-b2 receptor tyrosine kinase 2 (ERBB2)-specific binding were synthesized by base-pair hybridization using a complementary oligonucleotide platform.

Tumor-Targeted Erythrocyte Membrane Nanoparticles for Theranostics of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) cells do not contain various receptors for targeted treatment, a reason behind the poor prognosis of this disease. In this study, biocompatible theranostic erythrocyte-derived nanoparticles (EDNs) were developed and evaluated for effective early diagnosis and treatment of TNBC. The anti-cancer drug, doxorubicin (DOX), was encapsulated into the EDNs and diagnostic quantum dots (QDs) were incorporated into the lipid bilayers of EDNs for tumor bio-imaging.

Therapeutic Response Monitoring with Zr-DFO-Pertuzumab in HER2-Positive and Trastuzumab-Resistant Breast Cancer Models.

Immuno-positron emission tomography (PET) has great potential to evaluate the target expression level and therapeutic response for targeted cancer therapy. Immuno-PET imaging with pertuzumab, due to specific recognition in different binding sites of HER2, could be useful for the determination of the therapeutic efficacy of HER2-targeted therapy, trastuzumab, and heat shock protein 90 (HSP90) inhibitor, in HER2-expressing breast cancer. The aim of this study is to evaluate the feasibility of monitoring therapeutic response with Zr-DFO-pertuzumab for the treatment of HER2-targeted therapeutics, trastuzumab, or the HSP90 inhibitor 17-DMAG, in trastuzumab-resistant JIMT-1 breast cancer models.

An antibody against L1 cell adhesion molecule inhibits cardiotoxicity by regulating persistent DNA damage.

Targeting the molecular pathways underlying the cardiotoxicity associated with thoracic irradiation and doxorubicin (Dox) could reduce the morbidity and mortality associated with these anticancer treatments. Here, we find that vascular endothelial cells (ECs) with persistent DNA damage induced by irradiation and Dox treatment exhibit a fibrotic phenotype (endothelial-mesenchymal transition, EndMT) correlating with the colocalization of L1CAM and persistent DNA damage foci. We demonstrate that treatment with the anti-L1CAM antibody Ab417 decreases L1CAM overexpression and nuclear translocation and persistent DNA damage foci.

CXCR4 uses STAT3-mediated slug expression to maintain radioresistance of non-small cell lung cancer cells: emerges as a potential prognostic biomarker for lung cancer.

Lung cancer is one of the most common reasons for cancer-induced mortality across the globe, despite major advancements in the treatment strategies including radiotherapy and chemotherapy. Existing reports suggest that CXCR4 is frequently expressed by malignant tumor and is imperative for vascularization, tumor growth, cell migration, and metastasis pertaining to poor prognosis. In this study, we infer that CXCR4 confers resistance to ionizing radiation (IR) in nonsmall cell lung cancer (NSCLC) cells.

Small Animal PET Imaging of hTERT RNA-Targeted HSV1-tk Gene Expression with Splicing Ribozyme.

splicing ribozymes (TSR) are useful anticancer agents targeting cancer-specific transcripts and replacing the RNA to induce anticancer gene expression specifically and selectively in cancer cells. Similar to other gene therapy methods, it is also important to evaluate the transgene expression for target specificity and ribozyme activity. In this study, the authors performed small animal positron emission tomography (PET) imaging and biodistribution assay to evaluate human telomerase reverse transcriptase (hTERT) RNA-targeting-specific TSR, which directs the expression of herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene selectively in hTERT-positive tumors through targeted RNA replacement of the hTERT transcript.

Development of a Theranostic Convergence Bioradiopharmaceutical for Immuno-PET Based Radioimmunotherapy of L1CAM in Cholangiocarcinoma Model.

Purpose: Cholangiocarcinoma is a malignancy of bile duct with a poor prognosis. Conventional chemotherapy and radiotherapy are generally ineffective, and surgical resection is the only curative treatment for cholangiocarcinoma. L1-cell adhesion molecule (L1CAM) has been known as a novel prognostic marker and therapeutic target for cholangiocarcinoma.

Biodegradable micro-sized discoidal polymeric particles for lung-targeted delivery system.

Various types of particle-based drug delivery systems have been explored for the treatment of pulmonary diseases; however, bio-distribution and elimination of the particles should be monitored for better understanding of their therapeutic efficacy and safety. This study aimed to characterize the biological properties of micro-sized discoidal polymeric particles (DPPs) as lung-targeted drug delivery carriers. DPPs were prepared using a top-down fabrication approach and characterized by assessing size and zeta potential.

Anti-EGF Receptor Aptamer-Guided Co-Delivery of Anti-Cancer siRNAs and Quantum Dots for Theranostics of Triple-Negative Breast Cancer.

Many aptamers have been evaluated for their ability as drug delivery vehicles to target ligands, and a variety of small interfering RNAs (siRNAs) have been tested for their anti-cancer properties. However, since these two types of molecules have similar physicochemical properties, it has so far been difficult to formulate siRNA-encapsulating carriers guided by aptamers. Here, we propose aptamer-coupled lipid nanocarriers encapsulating quantum dots (QDs) and siRNAs for theragnosis of triple-negative breast cancer (TNBC).

PET imaging of HER2 expression with an 18F-fluoride labeled aptamer.

Background/purpose: Aptamers are oligonucleotide or peptide molecules that bind to a target molecule with high affinity and specificity. The present study aimed to evaluate the target specificity and applicability for in vivo molecular imaging of an aptamer labeled with a radioisotope.

Methods: The human epidermal growth factor receptor 2 (HER2/ErbB2) aptamer was radiolabeled with 18F-fluoride.

PET Imaging Biomarkers of Anti-EGFR Immunotherapy in Esophageal Squamous Cell Carcinoma Models.

Epidermal growth factor receptor (EGFR) is overexpressed and considered as a proper molecular target for diagnosis and targeted therapy of esophageal squamous cell carcinoma (ESCC). This study evaluated the usefulness of PET imaging biomarkers with Cu-PCTA-cetuximab and F-FDG-PET for anti-EGFR immunotherapy in ESCC models. EGFR status and glucose metabolism by cetuximab treatment were evaluated using Cu-PCTA-cetuximab and F-FDG-PET, respectively.

Anti-EGFR lipid micellar nanoparticles co-encapsulating quantum dots and paclitaxel for tumor-targeted theranosis.

Cancer theranosis is an emerging field of personalized medicine which enables individual anti-cancer treatment by monitoring the therapeutic responses of cancer patients. Based on a consideration of the nano-bio interactions related to the blood circulation of systemically administered nanoparticles in humans, as well as extravasation and active targeting, lipid micellar nanoparticles were co-loaded with paclitaxel (PTX) and quantum dots (QDs) to generate a theranostic delivery vehicle. To provide with a tumor-targeting capability, either an antibody or an aptamer against the epidermal growth factor receptor (EGFR) was conjugated to the micelle surface.

Development of Cu-NOTA-Trastuzumab for HER2 Targeting: A Radiopharmaceutical with Improved Pharmacokinetics for Human Studies.

The purpose of this study was to develop Cu-labeled trastuzumab with improved pharmacokinetics for human epidermal growth factor receptor 2 (HER2). Trastuzumab was conjugated with SCN-Bn-NOTA and radiolabeled with Cu. Serum stability and immunoreactivity of Cu-NOTA-trastuzumab were tested.

Intense Red-Emitting Upconversion Nanophosphors (800 nm-Driven) with a Core/Double-Shell Structure for Dual-Modal Upconversion Luminescence and Magnetic Resonance in Vivo Imaging Applications.

In this study, intense single-band red-emitting upconversion nanophosphors (UCNPs) excited with 800 nm near-infrared (NIR) light are reported. When a NaYF:Nd,Yb active-shell is formed on the 12.7 nm sized NaGdF:Yb,Ho,Ce UCNP core, the core/shell (C/S) UCNPs show tunable emission from green to red, depending on the Ce concentration under excitation with 800 nm NIR light.

Facile metabolic glycan labeling strategy for exosome tracking.

Background: Exosomes are nano-sized vesicles derived from the fusion of multivesicular bodies with the surrounding plasma membrane. Exosomes have various diagnostic and therapeutic potentials in cancer and other diseases, thus tracking exosomes is an important issue.

Methods: Here, we report a facile exosome labeling strategy using a natural metabolic incorporation of an azido-sugar into the glycan, and a strain-promoted azide-alkyne click reaction.

A cell surface clicked navigation system to direct specific bone targeting.

Cell therapies are promising up-and-coming therapeutic strategies for many diseases. For maximal therapeutic benefits, injected cells have to navigate their way to a designated area, including organ and tissue; unfortunately, the majority of therapeutic cells are currently administered without a guide or homing device. To improve this serious shortcoming, a functionalization method was developed to equip cells with a homing signal.

Immuno-PET imaging based radioimmunotherapy in head and neck squamous cell carcinoma model.

The epidermal growth factor receptor (EGFR) is one of the most comprehensively studied molecular targets in head and neck squamous cell carcinoma (HNSCC). However, inherent and acquired resistance are serious problems and are responsible for limited clinical efficacy and tumor recurrence. In this study, we evaluated the feasibility of immuno-positron emission tomography (PET) imaging and radioimmunotherapy (RIT) with Cu-/Lu-PCTA-cetuximab in cetuximab-resistant SNU-1066 HNSCC xenografted model.

Cancer-targeted Nucleic Acid Delivery and Quantum Dot Imaging Using EGF Receptor Aptamer-conjugated Lipid Nanoparticles.

Co-application of fluorescent quantum dot nanocrystals and therapeutics has recently become a promising theranostic methodology for cancer treatment. We developed a tumor-targeted lipid nanocarrier that demonstrates notable efficacy in gene delivery as well as tumor bio-imaging. Coupling of aptamer molecules against the EGF receptor (EGFR) to the distal termini of lipid nanoparticles provided the carrier with tumor-specific recognition capability.

Monitoring of macrophage accumulation in statin-treated atherosclerotic mouse model using sodium iodide symporter imaging system.

Introduction: Macrophages play a key role in atherosclerotic plaque formation in atherosclerosis, but its detailed understanding has poorly investigated until now. Thus, we sought to demonstrate a noninvasive technique for macrophage tracking to atherosclerotic lesions in apolipoprotein E(ApoE) mice with an imaging system based on sodium iodide symporter (NIS) gene coupled with Tc-single-photon emission computed tomography (SPECT).

Methods And Results: Macrophage cells (RAW264.

Combination of anti-L1 cell adhesion molecule antibody and gemcitabine or cisplatin improves the therapeutic response of intrahepatic cholangiocarcinoma.

Cholangiocarcinoma has a poor prognosis and is refractory to conventional chemotherapy and radiation therapy. Improving survival of patients with advanced cholangiocarcinoma urgently requires the development of new effective targeted therapies in combination with chemotherapy. We previously developed a human monoclonal antibody (mAb) Ab417 that binds to both the human and mouse L1 cell adhesion molecule (L1CAM) with high affinities.