Development of radioligands with an albumin-binding moiety of 4-(P-Iodophenyl) butyric acid for theranostic applications.

The rapid clearance of imaging probes from blood circulation is beneficial for receptor imaging, as it minimizes non-target tissue exposure and improves tumor-to-background contrast. However, this rapid clearance can hinder radioligand therapy by limiting tumor uptake of radiolabeled compounds. An optimal blood half-life is crucial, as it enhances the uptake of radiolabeled compounds in targets, improving tumor uptake and retention of small molecule drugs, and thus therapeutic outcomes.

FAP-targeted delivery of radioiodinated probes: A progressive albumin-driven strategy for tumor theranostics.

Fibroblasts activated protein (FAP) appears to be a promising target for tumor theranostics. However, the development of radioiodinated probes for FAP has been slow. In this study, a progressive abumin-driven strategy was adopted to improve the FAP-targeted delivery of radioiodinated probes for tumor theranostics.

Modification of Asp-Peptide Adapters: Giving the FAP-Targeted Radioligand a "Squirrel Tail".

Fibroblast activation protein (FAP) is a promising target for cancer theranostics, but most FAP-targeted radioprobes showed relatively insufficient tumor uptake and retention, which seriously hampered their further application. Inspired by the squirrel tail, this study developed a novel FAP-targeted molecule, FSND, which is modified with three Asp-peptide adapters to enable both Ga ([Ga]Ga-FSND) and F ([F]AlF-FSND) PET imaging. Compared to [Ga]Ga-FAPI-04, [Ga]Ga-FAPI-42, and [F]AlF-FAPI-42, [F]AlF-FSND and [Ga]Ga-FSND showed enhanced tumor uptake and prolonged residence in HT-1080-FAP and pancreatic tumor models, demonstrating the effectiveness of Asp-peptide adapters in pharmacomodulating FAP-targeted radioligands.

Small-Molecule Radiotracers for Visualization of V-Domain Immunoglobulin Suppressor of T Cell Activation.

V-domain immunoglobulin suppressor of T cell activation (VISTA) plays a critical role in regulating innate and adaptive immune responses within the tumor immune microenvironment. Quantifying VISTA expression is necessary to determine whether patients respond to a related combination immunotherapy. This study developed two Ga-labeled small-molecule probes ([Ga]Ga-DCA and [Ga]Ga-DNCA) for visualizing and differentiating VISTA expression.

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.

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.

Progressive Optimization of Lanthanide Nanoparticle Scintillators for Enhanced Triple-Activated Radioluminescence Imaging.

Lanthanide nanoparticle (LnNP) scintillators exhibit huge potential in achieving radionuclide-activated luminescence (radioluminescence, RL). However, their structure-activity relationship remains largely unexplored. Herein, progressive optimization of LnNP scintillators is presented to unveil their structure-dependent RL property and enhance their RL output efficiency.

Rational Design and Comparison of Novel Tc-Labeled FAPI Dimers for Visualization of Multiple Tumor Types.

Recognizing the significance of SPECT in nuclear medicine and the pivotal role of fibroblast activation protein (FAP) in cancer diagnosis and therapy, this study focuses on the development of Tc-labeled dimeric HF with high tumor uptake and image contrast. The dimeric HF was synthesized and radiolabeled with Tc in one pot using various coligands (tricine, TPPTS, EDDA, and TPPMS) to yield [Tc]Tc-TPPTS-HF, [Tc]Tc-EDDA-HF, and [Tc]Tc-TPPMS-HF dimers. SPECT imaging results indicated that [Tc]Tc-TPPTS-HF exhibited higher tumor uptake and tumor-to-normal tissue (T/NT) ratio than [Tc]Tc-EDDA-HF and [Tc]Tc-TPPMS-HF.

F-Labeled Amidobenzimidazole Analogue for Visualizing STING Expression in Tumor.

The stimulator of interferon genes (STING) is pivotal in mediating STING-dependent type I interferon production, which is crucial for enhancing tumor rejection. Visualizing STING within the tumor microenvironment is valuable for STING-related treatments, yet the availability of suitable STING imaging probes is limited. In this study, we developed [F]AlF-ABI, a novel F-labeled agent featuring an amidobenzimidazole core structure, for positron emission tomography (PET) imaging of STING in B16F10 and CT26 tumors.

Ga-Labeled TMTP1 Modified with d-Amino Acid for Positron Emission Tomography Diagnosis of Highly Metastatic Hepatocellular Carcinoma.

TMTP1 (NVVRQ) has been proven to selectively target various highly metastatic tumor cells. Nonetheless, existing TMTP1 probes encounter challenges such as rapid blood clearance, limited tumor uptake, and inadequate suitability for therapeutic interventions. To overcome these constraints, we designed and synthesized eight peptide probes, employing innovative chemical modification strategies involving d-amino acid modification and retro-inverso isomerization.

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.

Development of F-Labeled Acridone Analogue for Tumor Imaging via Stimulator of Interferon Genes Targeting.

The stimulator of interferon genes (STING) is a pivotal protein in the production of STING-dependent type I interferon, which has the potential to enhance tumor rejection. The visualization of STING in the tumor microenvironment is valuable for STING-related treatments, but few STING imaging probes have been reported to date. In this study, we developed a novel F-labeled agent ([F]F-CRI1) with an acridone core structure for the positron emission tomography (PET) imaging of STING in CT26 tumors.

Synthesis and Preclinical Evaluation of a Ga-Labeled Pyridine-Based Benzamide Dimer for Malignant Melanoma Imaging.

Benzamide (BZA), a small molecule that can freely cross cell membranes and bind to melanin, has served as an effective targeting group for melanoma theranostics. In this study, a novel pyridine-based BZA dimer (denoted as H-2) was labeled with Ga ([Ga]Ga-H-2) for positron emission tomography (PET) imaging of malignant melanomas. [Ga]Ga-H-2 was obtained with high radiochemical yield (98.

Development of a multi-scene universal multiple wavelet-FFT algorithm (MW-FFTA) for denoising motion artifacts in OCT-angiography in vivo imaging.

Optical coherence tomography angiography (OCTA) images suffer from inevitable micromotion (breathing, heartbeat, and blinking) noise. These image artifacts can severely disturb the visibility of results and reduce accuracy of vessel morphological and functional metrics quantization. Herein, we propose a multiple wavelet-FFT algorithm (MW-FFTA) comprising multiple integrated processes combined with wavelet-FFT and minimum reconstruction that can be used to effectively attenuate motion artifacts and significantly improve the precision of quantitative information.

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.

A novel F-labeled agonist for PET imaging of stimulator of interferon gene expression in tumor-bearing mice.

Purpose: Stimulator of interferon genes (STING) protein plays a vital role in the immune surveillance of tumor microenvironment. Monitoring STING expression in tumors benefits the relevant STING therapy. This study aimed to develop a novel F-labeled agonist, dimeric amidobenzimidazole (diABZI), and firstly evaluate the feasibility of noninvasive positron emission tomography (PET) imaging of STING expression in the tumor microenvironment.

Ga-Labeled Maleimide for Blood Pool and Lymph PET Imaging through Covalent Bonding to Serum Albumin In Vivo.

This study aims to develop a novel Ga-labeled tracer, which can covalently bind to albumin in vivo based on the maleimide-thiol strategy, and to evaluate its potential applications using positron emission tomography (PET). Ga-labeled maleimide-monoamide-DOTA (denoted as [Ga]Ga-DM) was prepared conveniently with a high radiochemical yield (>90%) and radiochemical purity (>99%). Its molar activity was calculated as 249.

Micro-SPECT Imaging of Acute Ischemic Stroke with Radioiodinated Riboflavin in Rat MCAO Models via Riboflavin Transporter Targeting.

Riboflavin transporter-3 (RFVT3) is a recently discovered and novel biomarker for the theranostics of nervous system diseases. RFVT3 is significantly overexpressed in cerebral injury after ischemic stroke. Herein, we first reported an RFVT3-targeted tracer I-riboflavin (I-RFLA) for SPECT imaging of ischemic stroke .

Rational Design and Pharmacomodulation of Protein-Binding Theranostic Radioligands for Targeting the Fibroblast Activation Protein.

The fibroblast activation protein (FAP), overexpressed on cancer-associated fibroblasts (CAFs), has become a valuable target for tumor diagnosis and therapy. However, most FAP-based radioligands show insufficient tumor uptake and retention. In this study, three novel albumin-binding FAP ligands (denoted as FSDDI, FSDDI, and FSDDI) were labeled with Ga and Lu to overcome these limitations.

A Paradigm of Cancer Immunotherapy Based on 2-[18F]FDG and Anti-PD-L1 mAb Combination to Enhance the Antitumor Effect.

Purpose: Efforts have been devoted to select eligible candidates for PD-1/PD-L1 immune checkpoint blocker (ICB) immunotherapy. Here, we have a serendipitous finding of positron emission tomography (PET) imaging tracer 2-[18F]FDG as a potential immunomodulator. Therefore, we hypothesize that 2-[18F]FDG could induce PD-L1 expression change and create an immune-favorable microenvironment for tumor immunotherapy.

MicroPET imaging of bacterial infection with nitroreductase-specific responsive F-labelled nitrogen mustard analogues.

Purpose: Bacterial infection and antibiotic resistance are serious threats to human health. This study aimed to develop two novel radiotracers, F-NTRP and F-NCRP, that possess a specific nitroreductase (NTR) response to image deep-seated bacterial infections using positron emission tomography (PET). This method can distinguish infection from sterile inflammation.