Oxygen-delivery nanoparticles enhanced immunotherapy efficacy monitored by granzyme B PET imaging in malignant tumors.

Limited treatment response and inadequate monitoring methods stand firmly before successful immunotherapy. Recruiting and activating immune cells in the hypoxic tumor microenvironment is the key to reversing immune suppression and improving immunotherapy efficacy. In this study, biomimetic oxygen-delivering nanoparticles (CmPF) are engineered for homologous targeting and hypoxia alleviation within the tumor environment.

Phase I study of [Ga]Ga-HX01 for targeting integrin αvβ3 and CD13 in healthy and malignancy subjects.

Purpose: Noninvasive angiogenesis visualization is essential for evaluating tumor proliferation, progression, invasion, and metastasis. This study aimed to translate the heterodimeric PET tracer [Ga]Ga-HX01, which targets integrin αvβ3 and CD13 in neovascularization, into phase I clinical study.

Methods: This study enrolled 12 healthy volunteers (phase Ia) and 10 patients with malignant tumors (phase Ib).

Evaluation of ()-, ()-, and ()-F-OF-NB1 for Imaging GluN2B Subunit-Containing -Methyl-d-Aspartate Receptors in Nonhuman Primates.

Despite 2 decades of research, no -methyl-d-aspartate (NMDA) glutamate receptor (GluN) subtype 2B (GluN1/2B) radioligand is yet clinically validated. Previously, we reported on ()-F-OF-NB1 as a promising GluN1/2B PET probe in rodents and its successful application for the visualization of GluN2B-containing NMDA receptors in postmortem brain tissues of patients with amyotrophic lateral sclerosis. In the current work, we report on the characterization of ()-, ()-, and ()-F-OF-NB1 in nonhuman primates.

Synthesis of a new bifunctional NODA for bioconjugation with PSMA ligand and one-step AlF labeling.

The AlF labeling method is a relatively new approach that allows radiofluorination of biomolecules such as peptides and proteins in a one-step procedure and in an aqueous solution. However, instability of the complex of [AlF] with hexadentate chelator NOTA may attribute to the disassociation of free F and [AlF] and accumulation in bone. In this study, we designed and synthesized a new bifunctional pentadentate AlF-chelator p-SCN-PhPr-NODA as well as its nitro form p-NO-PhPr-NODA.

Comparison of three novel radiotracers for GluN2B-containing NMDA receptors in non-human primates: -[C]NR2B-Me, -[F]of-Me-NB1, and -[F]of-NB1.

The NMDA receptor GluN2B subunit is a target of interest in neuropsychiatric disorders but to date there is no selective radiotracer available to quantify its availability . Here we report direct comparisons in non-human primates of three GluN2B-targeting radioligands: -[C]NR2B-Me, -[F]OF-Me-NB1, and -[F]OF-NB1. Plasma free fraction, metabolism, tissue distribution and kinetics, and quantitative kinetic modeling methods and parameters were evaluated in two adult rhesus macaques.

Translational PET Imaging of Spinal Cord Injury with the Serotonin Transporter Tracer [C]AFM.

Purpose: The descending raphespinal serotonin (5-HT) system contributes to neural activities required for locomotion. The presynaptic serotonin transporter (SERT) is a marker of 5-HT innervation. In this study, we explored the use of PET imaging with the SERT radioligand [C]AFM as a biomarker of 5-HT axon damage after spinal cord injury (SCI) in a rodent model and its translation to imaging SCI in humans.

New wine in old bottles: Ga-PSMA-11 PET/CT reveals COVID-19 in patients with prostate cancer.

The COVID-19 pandemic continues to influence every aspect of human life across the globe. It was reported that vascular angiogenesis of COVID-19 was elevated in patients with equally severe influenza virus infection. In this issue of AJNMMI, Farolfi et al.

Preclinical Advances in Theranostics for the Different Molecular Subtypes of Breast Cancer.

Breast cancer is the most common cancer in women worldwide. The heterogeneity of breast cancer and drug resistance to therapies make the diagnosis and treatment difficult. Molecular imaging methods with positron emission tomography (PET) and single-photon emission tomography (SPECT) provide useful tools to diagnose, predict, and monitor the response of therapy, contributing to precision medicine for breast cancer patients.

Biomimetic oxygen delivery nanoparticles for enhancing photodynamic therapy in triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is a kind of aggressive breast cancer with a high rate of metastasis, poor overall survival time, and a low response to targeted therapies. To improve the therapeutic efficacy and overcome the drug resistance of TNBC treatments, here we developed the cancer cell membrane-coated oxygen delivery nanoprobe, CCm-HSA-ICG-PFTBA, which can improve the hypoxia at tumor sites and enhance the therapeutic efficacy of the photodynamic therapy (PDT), resulting in relieving the tumor growth in TNBC xenografts.

Results: The size of the CCm-HSA-ICG-PFTBA was 131.

pH-Triggered Assembly of Natural Melanin Nanoparticles for Enhanced PET Imaging.

Natural melanin nanoplatforms have attracted attention in molecular imaging. Natural melanin can be made into small-sized nanoparticles, which penetrate tumor sites deeply, but unfortunately, the particles continue to backflow into the blood or are cleared into the surrounding tissues, leading to loss of retention within tumors. Here, we report a pH-triggered approach to aggregate natural melanin nanoparticles by introducing a hydrolysis-susceptible citraconic amide on the surface.

Synthesis and Preclinical Evaluation of a Ga-Radiolabeled Peptide Targeting Very Late Antigen-3 for PET Imaging of Pancreatic Cancer.

Pancreatic cancer is highly malignant and has a five-year survival rate of 5% due to an early lymph node, nerve, and vascular metastasis. Integrin αβ (also called very late antigen-3, VLA-3) is overexpressed in many tumors and plays a vital role in tumor formation, recurrence, and metastasis. In this study, we developed a Ga-radiolabeled peptide tracer targeting the α unit of VLA-3 and evaluated its potential application in positron emission computed tomography (PET) imaging of pancreatic cancer.

A thiopyrylium salt for PET/NIR-II tumor imaging and image-guided surgery.

All tumor imaging modalities have resolution limits below which deeply situated small metastatic foci may not be identified. Moreover, incomplete lesion excision will affect the outcomes of the patients. Scintigraphy is adept in locating lesions, and second near-infrared window (NIR-II) imaging may allow precise real-time tumor delineation.

Red blood cell membrane-coated upconversion nanoparticles for pretargeted multimodality imaging of triple-negative breast cancer.

Upconversion nanoparticles (UCNPs) have been widely employed for tumor imaging using magnetic resonance imaging (MRI) and upconversion luminescence (UCL) imaging. The short blood clearance time and immunogenicity of UCNPs have limited their further application in vivo. We have designed UCNPs camouflaged with an exterior red blood cell (RBC) membrane coating (RBC-UCNPs) to solve these problems.

Ultra-sensitive Nanoprobe Modified with Tumor Cell Membrane for UCL/MRI/PET Multimodality Precise Imaging of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer in which the estrogen receptor and progesterone receptor are not expressed, and human epidermal growth factor receptor 2 is not amplified or overexpressed either, which make the clinical diagnosis and treatment very challenging. Molecular imaging can provide an effective way to diagnose TNBC. Upconversion nanoparticles (UCNPs), are a promising new generation of molecular imaging probes.

Comparison of AlF- and Ga-labeled NOTA-PEG-LLP2A for PET imaging of very late antigen-4 in melanoma.

Malignant melanoma is an aggressive cancer with poor prognosis. Very late antigen-4 (VLA-4) is overexpressed in melanoma and many other tumors, making it an attractive target for developing molecular diagnostic and therapeutic agents. We compared AlF- and Ga-labeled LLP2A peptides for PET imaging of VLA-4 expression in melanoma.

Preclinical Evaluation of a Fluorine-18 (F)-Labeled Phosphatidylinositol 3-Kinase Inhibitor for Breast Cancer Imaging.

Breast cancer is one of the commonest malignancies in women, especially in middle-aged and elderly women. Abnormal activation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKt/mTOR) pathway has been found to be involved in breast cancer proliferation. Pictilisib (GDC-0941) is a potent inhibitor of PI3K with high affinity and is undergoing phase 2 clinical trials.