PET imaging of Mn labeled DOTATATE and DOTAJR11.

Manganese-52 is gaining interest as an isotope for PET imaging due to its desirable decay and chemical properties for radiopharmaceutical development. Somatostatin receptor 2 (SSTR2) is significantly overexpressed by neuroendocrine tumors (NETs) and is an important target for nuclear imaging and therapy. As an agonist, [Ga]Ga-DOTATATE has demonstrated significant internalization upon interaction with receptor ligands, whereas [Ga]Ga-DOTA-JR11(as an antagonist) exhibits limited internalization but better pharmacokinetics and increased tumor uptake.

SON-1010: an albumin-binding IL-12 fusion protein that improves cytokine half-life, targets tumors, and enhances therapeutic efficacy.

Background: Cytokines have been promising cancer immunotherapeutics for decades, yet only two are licensed to date. Interleukin-12 (IL-12) is a potent regulator of cell-mediated immunity that activates NK cells and interferon-γ (IFNγ) production. It plays a central role in multiple pathways that can enhance cancer cell death and modify the tumor microenvironment (TME).

Production of high purity Sc from proton irradiation of natural vanadium targets.

Background: Scandium-47 is the therapeutic counterpart to the diagnostic radionuclides, Sc and Sc. Together, these form elementally matched theranostic nuclide pairs, but their incorporation into radiopharmaceuticals requires developing production techniques leading to radioscandium isotopes with high chemical and radionuclidic purity. Previous Sc production methods involved expensive, enriched titanium targets that require additional procedures for target recovery.

Oxidative Injury to Lung Mitochondrial DNA is a Key Contributor for the Development of Chemical Lung Injury.

The mechanisms and extent to which inhalation of oxidant gases damage the mitochondrial genome contributing to the development of acute and chronic lung injury have not been investigated. C57BL/6 mice exposed to chlorine (Cl ) gas and returned to room air, developed progressive loss of lung DNA glycosylase OGG1, significant oxidative injury to mtDNA, decreased intact lung mitochondrial (mt) DNA, generation of inflammatory pathway by DAMPs causing airway and alveolar injury with significant mortality. Global proteomics identified over 1400 lung proteins with alteration of key mitochondrial proteins at 24 h post Cl exposure.

Development of Mn Labeled Trastuzumab for Extended Time Point PET Imaging of HER2.

Purpose: Due to their long circulation time in the blood, monoclonal antibodies (mAbs) such as trastuzumab, are usually radiolabeled with long-lived positron emitters for the development of agents for Positron Emission Tomography (PET) imaging. Manganese-52 (Mn, t = 5.6 d, β  = 29.

Cross section measurements for the production of Cr and Sc from proton irradiation of natural vanadium up to 24 MeV.

Scandium-47 is a promising radionuclide for targeted radiotherapy and is also an elementally matched therapeutic partner to Sc and Sc, which are suitable for Positron Emission Tomography. The predominantly reported routes for the production of Sc employ expensive enriched titanium or calcium targets to achieve high radionuclidic purity. This study reports measurements of the excitation function of the V(p,x)Sc reaction at proton energies of 18-24 MeV to optimize bombardment parameters for the production of Sc using this promising approach.

PET imaging of [52 Mn]Mn-DOTATATE and [52 Mn]Mn-DOTA-JR11.

Manganese-52 is gaining interest as an isotope for PET imaging due to its desirable decay and chemical properties for radiopharmaceutical development. Somatostatin receptor 2 (SSTR2) is significantly overexpressed by neuroendocrine tumors (NETs) and is an important target for nuclear imaging and therapy. As an agonist, [Ga]Ga-DOTATATE has demonstrated significant internalization upon interaction with receptor ligands, whereas [Ga]Ga-DOTA-JR11(as an antagonist) exhibits limited internalization but better pharmacokinetics and increased tumor uptake.

PET Imaging of Differentiated Thyroid Cancer with TSHR-Targeted [Zr]Zr-TR1402.

Thyroid cancer is the most common endocrine cancer, with differentiated thyroid cancers (DTCs) accounting for 95% of diagnoses. While most DTC patients are diagnosed and treated with radioiodine (RAI), up to 20% of DTC patients become RAI refractory (RAI-R). RAI-R patients have significantly reduced survival rates compared to patients who remain RAI-avid.

Impact of Bariatric Surgery on metabolic health in a Uruguayan cohort and the emerging predictive role of FSTL1.

Obesity poses significant challenges, necessitating comprehensive strategies for effective intervention. Bariatric Surgery (BS) has emerged as a crucial therapeutic approach, demonstrating success in weight loss and comorbidity improvement. This study aimed to evaluate the outcomes of BS in a cohort of 48 Uruguayan patients and investigate the interplay between BS and clinical and metabolic features, with a specific focus on FSTL1, an emerging biomarker associated with obesity and inflammation.

Improving the In Vivo Stability of [Mn]Mn(II) Complexes with 18-Membered Macrocyclic Chelators for PET Imaging.

We report the [Mn/Mn]Mn(II) complexes of the macrocyclic chelators PYAN [3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane] and CHXPYAN [(4,4,10,10)-3,5,9,11-tetraaza-1,7(2,6)-dipyridina-4,10(1,2)-dicyclohexanacyclododecaphane]. The X-ray crystal structures of Mn-PYAN and Mn-CHXPYAN evidence distorted octahedral geometries through coordination of the nitrogen atoms of the macrocycles. Cyclic voltammetry studies evidence reversible processes due to the Mn(II)/Mn(III) pair, indicating that the complexes are resistant to oxidation.

Evaluating the immunologically "cold" tumor microenvironment after treatment with immune checkpoint inhibitors utilizing PET imaging of CD4 + and CD8 + T cells in breast cancer mouse models.

Background: Immune-positron emission tomography (PET) imaging with tracers that target CD8 and granzyme B has shown promise in predicting the therapeutic response following immune checkpoint blockade (ICB) in immunologically "hot" tumors. However, immune dynamics in the low T-cell infiltrating "cold" tumor immune microenvironment during ICB remain poorly understood. This study uses molecular imaging to evaluate changes in CD4 + T cells and CD8 + T cells during ICB in breast cancer models and examines biomarkers of response.

Cryopreserved Thyroid Tissue Autotransplant in Pediatric Age Patients: A Feasibility Study and Literature Review.

Background And Aims: This paper aims to study an alternative solution to hormonal replacement therapy in specific groups of patients who underwent thyroidectomy during childhood or adulthood. After cryopreservation, thyroid autotransplantation could be an alternative solution which would allow us to use the ability of the thyroid tissue of producing hormones according to the physiological needs of the body.

Materials And Methods: A feasibility study about the effects of the most modern cryopreservation techniques on the structural and functional integrity of the follicular cells of the thyroid tissue has been carried out.

Production and separation of Be for use in an ion source.

Beryllium-7 (Be) was created by proton irradiation of natural (B) and enriched (B) boron targets. The targets were dissolved in nitric acid, and the Be was separated from the bulk boron target material by cation-exchange chromatography. An average recovery of (99.

Production and regulatory issues for theranostics.

Theranostics has become a major area of innovation and progress in cancer care over the last decade. In view of the introduction of approved therapeutics in neuroendocrine tumours and prostate cancer in the last 10 years, the ability to provide access to these treatments has emerged as a key factor in ensuring global benefits from this cancer therapy approach. In this Series paper we explore the issues that affect access to and availability of theranostic radiopharmaceuticals, including supply and regulatory issues that might affect the availability of theranostic treatments for patients with cancer.

[F]FMISO-PET imaging reveals the role of hypoxia severity in checkpoint blockade response.

Context: Hypoxia within the tumor microenvironment is a critical factor influencing the efficacy of immunotherapy, including immune checkpoint inhibition. Insufficient oxygen supply, characteristic of hypoxia, has been recognized as a central determinant in the progression of various cancers. The reemergence of evofosfamide, a hypoxia-activated prodrug, as a potential treatment strategy has sparked interest in addressing the role of hypoxia in immunotherapy response.

Titanium-45 (Ti) Radiochemistry and Applications in Molecular Imaging.

Molecular imaging is an important part of modern medicine which enables the non-invasive identification and characterization of diseases. With the advancement of radiochemistry and scanner technology, nuclear medicine is providing insight into efficient treatment options for individual patients. Titanium-45 (Ti) is a lesser-explored radionuclide that is garnering increasing interest for the development of positron emission tomography (PET) radiopharmaceuticals.

Customizable Porphyrin Platform Enables Folate Receptor PET Imaging Using Copper-64.

Folate receptors including folate receptor α (FRα) are overexpressed in up to 90% of ovarian cancers. Ovarian cancers overexpressing FRα often exhibit high degrees of drug resistance and poor outcomes. A porphyrin chassis has been developed that is readily customizable according to the desired targeting properties.

Construction of the Bioconjugate Py-Macrodipa-PSMA and Its In Vivo Investigations with Large La and Small Sc Radiometal Ions.

To harness radiometals in clinical settings, a chelator forming a stable complex with the metal of interest and targets the desired pathological site is needed. Toward this goal, we previously reported a unique set of chelators that can stably bind to both large and small metal ions, via a conformational switch. Within this chelator class, py-macrodipa is particularly promising based on its ability to stably bind several medicinally valuable radiometals including large La, Bi, and small Sc.

Dual anti-HER2/EGFR inhibition synergistically increases therapeutic effects and alters tumor oxygenation in HNSCC.

Epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and hypoxia are associated with radioresistance. The goal of this study is to study the synergy of anti-HER2, trastuzumab, and anti-EGFR, cetuximab, and characterize the tumor microenvironment components that may lead to increased radiation sensitivity with dual anti-HER2/EGFR therapy in head and neck squamous cell carcinoma (HNSCC). Positron emission tomography (PET) imaging ([Zr]-panitumumab and [Zr]-pertuzumab) was used to characterize EGFR and HER2 in HNSCC cell line tumors.

Evaluation of a novel hexadentate 1,2-hydroxypyridinone-based acyclic chelate, HOPO-O-C4, for Sc/Sc, Ga, and Ti radiopharmaceuticals.

Introduction: Chelators play a crucial role in the development of metal-based radiopharmaceuticals, and with the continued interest in Ga and increasing availability of new radiometals such as Sc/Sc and Ti, there is a growing demand for tailored chelators that can form stable complexes with these metals. This work reports the synthesis and characterization of a hexadentate tris-1,2-hydroxypyridonone chelator HOPO-O-C4 and its in vitro and in vivo evaluation with the above mentioned radiometals.

Methods: To investigate the affinity of HOPO-O-C4, macroscopic studies were performed with Sc, and Ga followed by DFT structural optimization of the Sc, Ga and Ti complexes.

[Zr]-CD8 ImmunoPET imaging of glioblastoma multiforme response to combination oncolytic viral and checkpoint inhibitor immunotherapy reveals CD8 infiltration differential changes in preclinical models.

Novel immune-activating therapeutics for the treatment of glioblastoma multiforme (GBM) have shown potential for tumor regression and increased survival over standard therapies. However, immunotherapy efficacy remains inconsistent with response assessment being complicated by early treatment-induced apparent radiological tumor progression and slow downstream effects. This inability to determine early immunotherapeutic benefit results in a drastically decreased window for alternative, and potentially more effective, treatment options.