Positron Emission Tomography Imaging of Cathepsin B in Tumors with Activable Small Molecule Tracers.

Cathepsin B (CTB) is overexpressed in several types of tumors, and precise evaluation of the CTB activity can offer a promising method for the early diagnosis of tumors. In this study, two CTB-activated positron emission tomography (PET) tracers, and , were developed for sensitive and specific detection of CTB. Both tracers undergo a click condensation between 2-cyano-6-aminobenzothiazole (CBT) and cysteine (Cys) to form a cyclization product, thereby enhancing and prolonging the PET signal in tumors.

Pyrotinib induces cell death in HER2-positive breast cancer via triggering HSP90-dependent HER2 degradation and ROS/HSF-1-dependent oxidative DNA damage.

HER2-positive breast cancer (HER2+ BC) is distinguished by its poor prognosis, propensity for early onset, and high risk of recurrence and metastasis. Consequently, anti-HER2-targeted therapy has emerged as a principal strategy in the treatment of this form of breast cancer. Pyrotinib, a novel irreversible pan-HER2 tyrosine kinase inhibitor, has brought fresh hope to patients with advanced HER2+ breast cancer.

Fine needle aspiration cytology diagnoses of follicular thyroid carcinoma: results from a multicenter study in Asia.

Background: This study was designed to compare diagnostic categories of thyroid fine needle aspiration cytology (FNAC) and incidence of thyroid tumors in the multi-institutional Asian series with a special focus on diagnostic category IV (suspicious for a follicular neoplasm) and follicular thyroid carcinomas (FTCs).

Methods: Distribution of FNAC categories, incidence of thyroid tumors in resection specimens and cytologic diagnoses of surgically confirmed follicular adenomas (FAs) and FTCs were collected from 10 institutes from five Asian countries and were compared among countries and between FAs and FTCs.

Results: The frequency of category IV diagnoses (3.

Value of [Ga]Ga-NYM046 PET/CT, in Comparison with F-FDG PET/CT, for Diagnosis of Clear Cell Renal Cell Carcinoma.

This study aimed to investigate the diagnostic efficacy of [Ga]Ga-NYM046 PET/CT in animal models and patients with clear cell renal cell carcinoma (ccRCC) and to compare its performance with that of F-FDG PET/CT. The in vivo biodistribution of [Ga]Ga-NYM046 was evaluated in mice bearing OS-RC-2 xenografts. Twelve patients with ccRCC were included in the study; all completed paired [Ga]Ga-NYM046 PET/CT and F-FDG PET/CT.

Synthesis and immunotherapy efficacy of a PD-L1 small-molecule inhibitor combined with its I-iodide labelled isostructural compound.

Although antibody-based immune checkpoint blockades have been successfully used in antitumor immunotherapy, the low response rate is currently the main problem. In this work, a small-molecule programmed cell death-ligand (PD-L1) inhibitor, LG-12, was developed and radiolabeled with I to obtain the chemically and biologically identical radiopharmaceutical [I]LG-12, which aimed to improve the antitumor effect by combination of LG-12 and [I]LG-12. LG-12 showed high inhibitory activity to PD-1/PD-L1 interaction.

STAT3 inhibitor Stattic Exhibits the Synergistic Effect with FGFRs Inhibitor Erdafitinib in FGFR1-positive Lung Squamous Cell Carcinoma.

Lung squamous cell carcinoma (LUSC), a subset of non-small cell lung cancer (NSCLC), accounts for about 30% of all lung cancers (LC) and exhibits a dismal response to current therapeutic protocols. Existed studies have indicated that aberrations in fibroblast growth factor receptors (FGFRs) play a pivotal role in the progression of LUSC, rendering them as attractive targets for therapeutic intervention in this cancer type. This study found that Erdafitinib (Erda), a novel pan-FGF receptor tyrosine kinase inhibitor (TKI), exerted a cytotoxic effect on LUSC cells.

Evaluation of damage discrimination in dopaminergic neurons using dopamine transporter PET tracer [F]FECNT-d.

Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder worldwide, diagnosed based on classic symptoms like motor dysfunction and cognitive impairments. With the development of various radioactive ligands, positron emission tomography (PET) imaging combined with specific radiolabelling probes has proven to be effective in aiding clinical PD diagnosis. Among these probes, 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[F]-fluoroethyl) nortropane ([F]FECNT) has been utilized as a PET tracer to image dopamine transporter (DAT) integrity in striatal presynaptic dopaminergic terminals.

The diagnostic value of Ga-NOTA-MAL-Cys-MZHER PET/CT imaging for HER2-positive lung adenocarcinoma.

Background: The human epidermal growth factor receptor 2 gene (HER2) has been identified as a potential therapeutic target in lung adenocarcinoma (LUAD). Non-invasive positron emission tomography (PET) imaging provides a reliable strategy for determination of HER2 expression through whole-body detection of abnormalities. The PET tracer Ga-NOTA-MAL-Cys-MZHER has shown promising results for HER2-positive breast and gastric cancers.

Preclinical Evaluation of a PSMA Aptamer-Based Bifunctional PET and Fluorescent Probe.

Prostate cancer is the most prevalent malignant tumor affecting male individuals worldwide. The accurate early detection of prostate cancer is crucial to preventing unnecessary diagnosis and subsequent excessive treatment. Prostate-specific membrane antigen (PSMA) has emerged as a promising biomarker for the diagnosis of prostate cancer.

Imaging Identifies Superior Inflammation Targeting of M1 Macrophages for Cryo-Shocked Cell Pulmonary Drug Delivery to Treat Acute Lung Injury.

In the realm of combating acute lung injury (ALI) induced by a myriad of triggers including sepsis, pneumonia, aspiration, trauma, and pancreatitis, macrophages emerge as crucial players. However, traditional treatments such as systemic administration of glucocorticoids come with the baggage of severe side effects, curtailing their utility. Enter an innovative solution: a biomimetic drug delivery system fashioned from cryo-shocked macrophages, tailored for pulmonary drug delivery.

A classic prescription alleviates inflammation in CUMS model mice via modulating MYDGF/MAP4K4/NF-κB signaling pathway, verified through UPLC-HRMS and proteomics analysis.

Background: Xiaoyaosan (XYS), a renowned classical traditional Chinese medicinal formula utilized in addressing major depressive disorder (MDD), has garnered significant acclaim for its remarkable efficacy in clinical application. The onset of major depressive disorder (MDD) often correlates with chronic unpredictable mild stress (CUMS), a pivotal instigating factor in its development.: This study aims to clarify the potential anti-inflammatory mechanisms of XYS in treating CUMS model mice.

Development of Granzyme B-targeted Smart Positron Emission Tomography Probes for Monitoring Tumor Early Response to Immunotherapy.

Granzyme B is an immune-related biomarker that closely correlates with cytotoxic T lymphocytes (CTLs), and hence detecting the expression level of granzyme B can provide a dependable scheme for clinical immune response assessment. In this study, two positron emission tomography (PET) probes [F]SF-M-14 and [F]SF-H-14 targeting granzyme B are designed based on the intramolecular cyclization scaffold SF. [F]SF-M-14 and [F]SF-H-14 can respond to granzyme B and glutathione (GSH) to conduct intramolecular cyclization and self-assemble into nanoaggregates to enhance the retention of probe at the target site.

Erdafitinib promotes ferroptosis in human uveal melanoma by inducing ferritinophagy and lysosome biogenesis via modulating the FGFR1/mTORC1/TFEB signaling axis.

Uveal melanoma (UM) is a rare yet lethal primary intraocular malignancy affecting adults. Analysis of data from The Cancer Genome Atlas (TCGA) database revealed that FGFR1 expression was increased in UM tumor tissues and was linked to aggressive behavior and a poor prognosis. This study assessed the anti-tumor effects of Erdafitinib, a selective pan-FGFR inhibitor, in both in vitro and in vivo UM models.

Targeted delivery of activatable I-radiopharmaceutical for sustained radiotherapy with improved pharmacokinetics.

Targeted radionuclide therapy (TRT) is an effective treatment for tumors. Self-condensation strategies can enhance the retention of radionuclides in tumors and enhance the anti-tumor effect. Considering legumain is overexpressed in multiple types of human cancers, a I-labeled radiopharmaceutical ([I]MAAN) based on the self-condensation reaction between 2-cyanobenzothiazole (CBT) and cysteine (Cys) was developed by us recently for treating legumain-overexpressed tumors.

Ultrasensitive detection of uveal melanoma using [F]AlF-NOTA-PRGD2 PET imaging.

Background: Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and early detection is critical to improve the clinical outcome of this disease. In this study, the diagnostic effectiveness of [F]AlF-NOTA-PRGD2 (an investigational medicinal product) positron emission tomography (PET) imaging in UM xenografts and UM patients were evaluated. The cell uptake, cell binding ability and in vitro stability of [F]AlF-NOTA-PRGD2 were evaluated in 92-1 UM cell line.

Comparison of Tumor Non-specific and PD-L1 Specific Imaging by Near-Infrared Fluorescence/Cerenkov Luminescence Dual-Modality In-situ Imaging.

Background: Labeled antibodies are excellent imaging agents in oncology to non-invasively visualize cancer-related antigens expression levels. However, tumor tracer uptake (TTU) of specific antibodies in-vivo may be inferior to non-specific IgG in some cases.

Objectives: To explore factors affecting labeled antibody visualization by PD-L1 specific and non-specific imaging of nude mouse tumors.

PET imaging for the early evaluation of ocular inflammation in diabetic rats by using [F]-DPA-714.

Ocular complications of diabetes mellitus (DM) are the leading cause of vision loss. Ocular inflammation often occurs in the early stage of DM; however, there are no proven quantitative methods to evaluate the inflammatory status of eyes in DM. The 18 kDa translocator protein (TSPO) is an evolutionarily conserved cholesterol binding protein localized in the outer mitochondrial membrane.

Design, Synthesis, and Biological Evaluation of Novel Nonsteroidal F-Labeled PET Probes Specifically Targeting Estrogen Receptor α.

The estrogen receptor α positive (ERα) subtype represents nearly 70% of all breast cancers (BCs), which seriously threaten women's health. Positron emission computed tomography (PET) characterizes its superiority in detecting the recurrence and metastasis of BC. In this article, an array of novel PET probes (, , , and ) targeting ERα based on the tetrahydropyridinyl indole scaffold were developed.

Synthesis and Characterization of a Novel PET Tracer for Noninvasive Evaluation of FGL1 Status in Tumors.

Fibrinogen-like protein 1 (FGL1) is a potential novel immune checkpoint target for malignant tumor diagnosis and therapy. Accurate detection of FGL1 levels in tumors via noninvasive PET imaging might be beneficial for managing the disease. To achieve this, multiple FGL1-targeting peptides (FGLP) were designed, and a promising candidate, Ga-NOTA-FGLP2, was identified through a high-throughput screening approach using microPET imaging of Ga-labeled peptides.