Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study.

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the stability, pharmacokinetics, and pharmacodynamics of Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, Lu-LNC1010, for PRRT.

Generation of induced pluripotent stem cell-derived anterior foregut endoderms on integrin-binding short peptide-based synthetic substrates.

Anterior foregut endoderms (AFEs) derived from induced pluripotent stem cells (iPSCs) are an important cell source in stem cell technology as they give rise to some important lineages like lung progenitors and thyroid cells. Coating substrates plays a critical role in AFE generation. Currently, conventional large molecule proteins like Matrigel are used in most differentiation protocols.

Dansylated Amino Acid-Modified Long-Acting PSMA Derivatives Ga/Lu-LNC1011 as Prostate Cancer Theranostics.

Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical therapy has demonstrated promising potential for treating metastatic castration-resistant prostate cancer. Recently, albumin-binding motif-modified PSMA radioligands with prolonged blood circulation were developed to improve tumor uptake and therapeutic effectiveness, properties which, however, were associated with an increased risk of bone marrow toxicity. This study presents new PSMA-targeted radioligands incorporating dansylated amino acids as relatively weak and preferable albumin binders to achieve a fine balance between increased tumor accumulation, safety, and diagnostic efficacy, facilitating a unified approach to theranostics within a single molecular framework.

Development of [Ac]Ac‑LNC1011 for targeted alpha-radionuclide therapy of prostate cancer.

Purpose: Prostate-specific membrane antigen (PSMA) radioligand therapy (PRLT) has become a promising option for treating metastatic castration-resistant prostate cancer (mCRPC). Radioligands labelled with the Ga/Lu theranostic pair have been most widely used in the clinic for diagnosis and therapy, respectively. This study aims to develop a novel PSMA-targeted radioligand, LNC1011, radiolabeled with alpha-emitter Ac, to optimise pharmacokinetic properties and assess its potential for targeted alpha therapy (TAT) in prostate cancer treatment.

Modified five times simulated body fluid for efficient biomimetic mineralization.

Simulated body fluid (SBF) is widely utilized in preclinical research for estimating the mineralization efficacy of biomaterials. Therefore, it is of great significance to construct an efficient and stable SBF mineralization system. The conventional SBF solutions cannot maintain a stable pH value and are prone to precipitate homogeneous calcium salts at the early stages of the biomimetic process because of the release of gaseous CO.

Engineered Antibodies as Cancer Radiotheranostics.

Radiotheranostics is a rapidly growing approach in personalized medicine, merging diagnostic imaging and targeted radiotherapy to allow for the precise detection and treatment of diseases, notably cancer. Radiolabeled antibodies have become indispensable tools in the field of cancer theranostics due to their high specificity and affinity for cancer-associated antigens, which allows for accurate targeting with minimal impact on surrounding healthy tissues, enhancing therapeutic efficacy while reducing side effects, immune-modulating ability, and versatility and flexibility in engineering and conjugation. However, there are inherent limitations in using antibodies as a platform for radiopharmaceuticals due to their natural activities within the immune system, large size preventing effective tumor penetration, and relatively long half-life with concerns for prolonged radioactivity exposure.

Expansion and differentiation of human neural stem cells on synthesized integrin binding peptide surfaces.

The extracellular matrix plays a crucial role in the growth of human neural stem cells (hNSCs) by forming a stem cell niche, bothand. The demand for defined synthetic substrates has been increasing recently in stem cell research, reflecting the requirements for precise functions and safety concerns in potential clinical approaches. In this study, we tested the adhesion and expansion of one of the most representative hNSC lines, the ReNcell VM Human Neural Progenitor Cell Line, in a pure-synthesized short peptide-basedniche using a previously established integrin-binding peptide array.

Generation of induced pluripotent stem cells from rat fibroblasts and optimization of its differentiation into mature functional neurons.

Background: Induced pluripotent stem cells (iPSCs) derived neural stem cells (NSCs) provide a potential for autologous neural transplantation therapy following neurological insults. Thus far, in preclinical studies the donor iPSCs-NSCs are mostly of human or mouse origin with concerns centering around graft rejection when applied to rat brain injury models. For better survival and integration of transplanted cells in the injured brain in rat models, use of rat-iPSC-NSCs and in combination with biomaterials is of advantageous.

Synthesis, preclinical, and initial clinical evaluation of integrin αβ and gastrin-releasing peptide receptor (GRPR) dual-targeting radiotracer [Ga]Ga-RGD-RM26-03.

Unlabelled: Integrin receptor αβ and gastrin-releasing peptide receptor (GRPR) expression of tumors could be detected using PET imaging with radiolabeled Arg-Gly-Asp (RGD) and the antagonistic bombesin analog RM26, respectively. The purpose of this study was to investigate the dual receptor-targeting property of the heterodimer RGD-RM26-03 (denoted as LNC1015), demonstrate the tumor diagnostic value of [Ga]Ga-LNC1015 in preclinical experiments, and evaluate its preliminary clinical feasibility.

Methods: LNC1015 was designed and synthesized by linking cyclic RGD and the RM26 peptide.

Development of small-molecular-based radiotracers for PET imaging of PD-L1 expression and guiding the PD-L1 therapeutics.

Purpose: Programmed cell death protein ligand 1 (PD-L1) is a crucial biomarker for immunotherapy. However, nearly 70% of patients do not respond to PD-L1 immune checkpoint therapy. Accurate monitoring of PD-L1 expression and quantification of target binding during treatment are essential.

Biomimetic crimped/aligned microstructure to optimize the mechanics of fibrous hybrid materials for compliant vascular grafts.

The precise mechanical properties of many tissues are highly dependent on both the composition and arrangement of the nanofibrous extracellular matrix. It is well established that collagen nanofibers exhibit a crimped microstructure in several tissues such as blood vessel, tendon, and heart valve. This collagen fiber arrangement results in the classic non-linear 'J-shaped' stress strain curve characteristic of these tissues.

Comparative Study of Radioiodinated Folate Receptor Targeting Albumin Probes for Atherosclerosis Plaque Imaging.

The objective of this study is to compare a series of albumin-based folate radiotracers for the potential imaging of folate receptor (FR) positive macrophages in advanced atherosclerotic plaques. Diversified radioiodinated FR-targeting albumin-binding probes ([I]IBAHF, [I]IBHF, and [I]HF) were developed through various strategies. Among the three radiotracers, [I]IBAHF and [I]IBHF showed excellent stability (>98%) in saline and PBS 7.

A Head-to-Head Comparison of 68Ga-LNC1007 and 2-18F-FDG/68Ga-FAPI-02 PET/CT in Patients With Various Cancers.

Objectives: This head-to-head comparison study was designed to investigate the radiotracer uptake and clinical feasibility of using 68Ga-LNC1007, to detect the primary and metastatic lesions in patients with various types of cancer, and to compare the results with those of 2-18F-FDG PET/CT and 68Ga-FAPI-02 PET/CT.

Patients And Methods: Sixty-one patients with 10 different kinds of cancers were enrolled in this study. Among them, 50 patients underwent paired 68Ga-LNC1007 and 2-18F-FDG PET/CT, and the other 11 patients underwent paired 68Ga-LNC1007 and 68Ga-FAPI-02 PET/CT.

Single-cell dissection of cervical cancer reveals key subsets of the tumor immune microenvironment.

The tumor microenvironment (TME) directly determines patients' outcomes and therapeutic efficiencies. An in-depth understanding of the TME is required to improve the prognosis of patients with cervical cancer (CC). This study conducted single-cell RNA and TCR sequencing of six-paired tumors and adjacent normal tissues to map the CC immune landscape.

Nanoparticle-Based Drug Delivery Systems: An Inspiring Therapeutic Strategy for Neurodegenerative Diseases.

Neurodegenerative diseases are common, incurable neurological disorders with high prevalence, and lead to memory, movement, language, and intelligence impairments, threatening the lives and health of patients worldwide. The blood-brain barrier (BBB), a physiological barrier between the central nervous system and peripheral blood circulation, plays an important role in maintaining the homeostasis of the intracerebral environment by strictly regulating the transport of substances between the blood and brain. Therefore, it is difficult for therapeutic drugs to penetrate the BBB and reach the brain, and this affects their efficacy.

Clinical Evaluation of Ga-FAPI-RGD for Imaging of Fibroblast Activation Protein and Integrin αβ in Various Cancer Types.

Radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) and Arg-Gly-Asp (RGD) peptides have been extensively investigated for imaging of FAP- and integrin αβ-positive tumors. In this study, a FAPI-RGD heterodimer was radiolabeled with Ga and evaluated in patients with cancer. We hypothesized that the heterodimer, recognizing both FAP and integrin αβ, would be advantageous because of its dual-receptor-targeting property.

A simple method to isolate structurally and chemically intact brain vascular basement membrane for neural regeneration following traumatic brain injury.

Background: The brain vascular basement membrane (brain-VBM) is an important component of the brain extracellular matrix, and the three-dimensional structure of the cerebrovascular network nested with many cell-adhesive proteins may provide guidance for brain tissue regeneration. However, the potential of ability of brain-VBM to promote neural tissue regeneration has not been examined due to the technical difficulty of isolating intact brain-VBM.

Methods: The present study developed a simple, effective method to isolate structurally and compositionally intact brain-VBM.

Targeting the activity of T cells by membrane surface redox regulation for cancer theranostics.

T cells play a determining role in the immunomodulation and prognostic evaluation of cancer treatments relying on immune activation. While specific biomarkers determine the population and distribution of T cells in tumours, the in situ activity of T cells is less studied. Here we designed T-cell-targeting fusogenic liposomes to regulate and quantify the activity of T cells by exploiting their surface redox status as a chemical target.

Age-dependent viscoelastic characterization of rat brain cortex.

Unlabelled: Recent efforts in biomaterial-assisted brain tissue engineering suggest that match of mechanical properties of biomaterials to those of native brain tissue may be crucial for brain regeneration. In particular, the mechanical properties of native brain tissue vary as a function of age. To date, detailed characterization of age-dependent viscoelastic properties of brain tissue throughout the postnatal development to adulthood is only available at sparse age points in animal studies.

Longitudinal MicroSPECT Imaging of Systemic Sclerosis Model Mice with [Tc]Tc-HYNFA via Folate Receptor Targeting.

Noninvasive single-photon emission computed tomography (SPECT) imaging with [Tc]Tc-HYNFA via folate receptor (FR) targeting was proposed to assess the inflammation and therapeutic effect of systemic sclerosis (SSc) in model mice. The radiochemical yield and purity of [Tc]Tc-HYNFA were over 95%, with a specific activity of about 9.36 ± 0.

Synthesis, preclinical evaluation and radiation dosimetry of a dual targeting PET tracer [Ga]Ga-FAPI-RGD.

To enhance tumor uptake and retention, we designed and developed bi-specific heterodimeric radiotracers targeting both FAP and αvβ3, [Ga]Ga-FAPI-RGD. The present study aimed to evaluate the specificity, pharmacokinetics, and dosimetry of [Ga]Ga-FAPI-RGD by preclinical and preliminary clinical studies. FAPI-RGD was designed and synthesized with the quinoline-based FAPI-02 and the cyclic RGDfK peptide.

Synergism of Cu-Labeled RGD with Anti-PD-L1 Immunotherapy for the Long-Acting Antitumor Effect.

We put forward a novel targeting-triggering-therapy (TTT) scheme that combines Cu-based targeted radionuclide therapy (TRT) with programmed death-ligand 1 (PD-L1)-based immunotherapy for enhancing therapeutic efficacy. The αβ integrin-targeted Cu-DOTA-EB-cRGDfK (Cu-DER) was synthesized. Flow cytometry, immunofluorescence staining, and RT-qPCR were performed to verify PD-L1 upregulation after irradiation with Cu-DER.

Integrin binding peptides facilitate growth and interconnected vascular-like network formation of rat primary cortical vascular endothelial cells .

Neovascularization and angiogenesis in the brain are important physiological processes for normal brain development and repair/regeneration following insults. Integrins are cell surface adhesion receptors mediating important function of cells such as survival, growth and development during tissue organization, differentiation and organogenesis. In this study, we used an integrin-binding array platform to identify the important types of integrins and their binding peptides that facilitate adhesion, growth, development, and vascular-like network formation of rat primary brain microvascular endothelial cells.