Multi-modality deep learning-based [Ga]Ga-DOTA-FAPI-04 PET polar map generation: potential value in detecting reactive fibrosis after myocardial infarction.

Purpose: Generating polar map (PM) from [Ga]Ga-DOTA-FAPI-04 PET images is challenging and inaccurate using existing automatic methods that rely on the myocardial anatomical integrity in PET images. This study aims to enhance the accuracy of PM generated from [Ga]Ga-DOTA-FAPI-04 PET images and explore the potential value of PM in detecting reactive fibrosis after myocardial infarction and assessing its relationship with cardiac function.

Methods: We proposed a deep-learning-based method that fuses multi-modality images to compensate for the cardiac structural information lost in [Ga]Ga-DOTA-FAPI-04 PET images and accurately generated PMs.

Development and Evaluation of DOTA-FAPI-Maleimide as a Novel Radiotracer for Tumor Theranostic with Extended Circulation.

This study aimed to evaluate a novel albumin-binding strategy for addressing the challenge of insufficient tumor retention of fibroblast activation protein inhibitors (FAPIs). Maleimide, a molecule capable of covalent binding to free thiol groups, was modified to conjugate with FAPI-04 in order to enhance its binding to endogenous albumin, resulting in an extended blood circulation half-life and increased tumor uptake. DOTA-FAPI-maleimide was prepared and radiolabeled with Ga-68 and Lu-177, followed by cellular assays, pharmacokinetic analysis, PET/CT, and SPECT/CT imaging to assess the probe distribution in various tumor-bearing models.

Targeting the glucocorticoid receptor-CCR8 axis mediated bone marrow T cell sequestration enhances infiltration of anti-tumor T cells in intracranial cancers.

Brain tumors such as glioblastomas are resistant to immune checkpoint blockade therapy, largely due to limited T cell infiltration in the tumors. Here, we show that mice bearing intracranial tumors exhibit systemic immunosuppression and T cell sequestration in bone marrow, leading to reduced T cell infiltration in brain tumors. Elevated plasma corticosterone drives the T cell sequestration via glucocorticoid receptors in tumor-bearing mice.

Development of Preladenant-Based Radiotracers for Imaging AR in Tumors.

Activation of the adenosine 2A receptor (AR) can lead to tumor immunosuppression, which results in poor prognosis of immunotherapy. The aim of this study was to design novel F-labeled probes ([F]F-PFP and [F]F-PFP) to visualize AR in the tumor. The uptake of radioprobes in AR-negative 4T1 breast tumor was lower than that of AR-positive B16F10 melanoma at 1 h p.

Engineered in vivo and in vitro tumor model recapitulates vasculogenic mimicry signatures in melanoma.

Vasculogenic mimicry (VM) describes a process by which tumor cells formed a novel microcirculation pattern in an endothelial cell-free manner. Clinically, VM is associated with aggressive phenotype and poor patient survival. However, the current models for investigating VM include 2D monolayer cultures, Matrigel-based cultures, and animal models, each of which has limitations.

An acid-activatable fluorouracil prodrug for colorectal cancer synergistic therapy.

5-Fluorouracil has demonstrated certain efficiency in patients with colorectal cancer. However, significant side effects of use by injection are common. To address this issue defects, a reengineered 5'-deoxy-5-fluorocytidine (DFCR) based drug delivery system (POACa) is developed as a prominent tumor-selective nano-activator.

An Overview of Appropriate Medical Practice and Preparedness in Radiation Emergency Response.

Radiation emergencies involving high doses of nuclear radiation pose significant risks from exposure to ionizing radiation in various scenarios. These situations include transportation accidents involving radioactive materials, occupational exposure, nuclear detonations, dirty bombs, and nuclear power plant accidents. In addition to the immediate risks of acute radiation syndrome (ARS) and related diseases, long-term exposure can increase the risk of other health issues such as cardiovascular disease and cancer.

Regional changes in brain metabolism during the progression of mild cognitive impairment: a longitudinal study based on radiomics.

Background: This study aimed to establish radiomics models based on positron emission tomography (PET) images to longitudinally predict transition from mild cognitive impairment (MCI) to Alzheimer's disease (AD).

Methods: In our study, 278 MCI patients from the ADNI database were analyzed, where 60 transitioned to AD (pMCI) and 218 remained stable (sMCI) over 48 months. Patients were divided into a training set (n = 222) and a validation set (n = 56).

Immunogenicity of Extracellular Vesicles.

Extracellular vesicles (EVs) are promising next-generation therapeutics and drug delivery systems due to demonstrated safety and efficacy in preclinical models and early-stage clinical trials. There is an urgent need to address the immunogenicity of EVs (beyond the apparent lack of immunotoxicity) to advance clinical development. To date, few studies have assessed unintended immunological recognition of EVs.

Nanoscale Metal-Organic Layer Reprograms Cellular Metabolism to Enhance Photodynamic Therapy and Antitumor Immunity.

Abnormal cancer metabolism causes hypoxic and immunosuppressive tumor microenvironment (TME), which limits the antitumor efficacy of photodynamic therapy (PDT). Herein, we report a photosensitizing nanoscale metal-organic layer (MOL) with anchored 3-bromopyruvate (BrP), BrP@MOL, as a metabolic reprogramming agent to enhance PDT and antitumor immunity. BrP@MOL inhibited mitochondrial respiration and glycolysis to oxygenate tumors and reduce lactate production.

Sex hormones in COVID-19 severity: The quest for evidence and influence mechanisms.

Studies have reported variable effects of sex hormones on serious diseases. Severe disease and mortality rates in COVID-19 show marked gender differences that may be related to sex hormones. Sex hormones regulate the expression of the viral receptors ACE2 and TMPRSS2, which affect the extent of viral infection and consequently cause variable outcomes.

Lysosome-Targeted and pH-Activatable Phototheranostics for NIR-II Fluorescence Imaging-Guided Nasopharyngeal Carcinoma Phototherapy.

Currently, clinical therapeutic strategies for nasopharyngeal carcinoma (NPC) confront insurmountable dilemmas in which surgical resection is incomplete and chemotherapy/radiotherapy has significant side effects. Phototherapy offers a maneuverable, effective, and noninvasive pattern for NPC therapy. Herein, we developed a lysosome-targeted and pH-responsive nanophototheranostic for near-infrared II (NIR-II) fluorescence imaging-guided photodynamic therapy (PDT) and photothermal therapy (PTT) of NPC.

A robotic system for automated chemical synthesis of therapeutic agents.

The development of novel compounds for tissue-specific targeting and imaging is often impeded by a lack of lead compounds and the availability of reliable chemistry. Automated chemical synthesis systems provide a potential solution by enabling reliable, repeated access to large compound libraries for screening. Here we report an integrated solid-phase combinatorial chemistry system created using commercial and customized robots.

A Review of Image Sensors Used in Near-Infrared and Shortwave Infrared Fluorescence Imaging.

To translate near-infrared (NIR) and shortwave infrared (SWIR) fluorescence imaging into the clinic, the paired imaging device needs to detect trace doses of fluorescent imaging agents. Except for the filtration scheme and excitation light source, the image sensor used will finally determine the detection limitations of NIR and SWIR fluorescence imaging systems. In this review, we investigate the current state-of-the-art image sensors used in NIR and SWIR fluorescence imaging systems and discuss the advantages and limitations of their characteristics, such as readout architecture and noise factors.

Repurposing indocyanine green: exploring the potential of an old drug in modern medicine.

The repurposing of existing drugs, referred to as theranostics, has made profound impacts on precision medicine. Indocyanine green (ICG), a well-established and clinical dye, has continued to be a star agent, described as a multifunctional molecule with concurrent photo- or sono-sensitiveness capabilities and co-delivery accessibility, showing remarkable potential in the area of unimodal or multimodal imaging-guided therapy of various diseases, leading to the extensive consideration of immediate clinical translations. In this review, we strive to bring the understanding of repurposing performance assessment for ICG into practice by clarifying the relationships between its features and applicability.

Neuroprotective effects of anti-TRAIL-ICG nanoagent and its multimodal imaging evaluation in cerebral ischemia-reperfusion injury.

Cerebral ischemia-reperfusion injury (CIRI) is a major challenge to neuronal survival in acute ischemic stroke (AIS). However, effective neuroprotective agents remain to be developed for the treatment of CIRI. In this work, we have developed an Anti-TRAIL protein-modified and indocyanine green (ICG)-responsive nanoagent (Anti-TRAIL-ICG) to target ischemic areas and then reduce CIRI and rescue the ischemic penumbra.