Separation of terbium from proton-irradiated gadolinium oxide targets - development of an effective, scalable and automatable process.

This work reports an effective and scalable radiochemical separation process for isolating terbium from GdO. The separation process uses three commercially available extraction chromatography resin columns, has been implemented on a computer-controlled chemistry module, and tested with 100 mg quantities of proton-irradiated GdO. The 4 h separation procedure isolated radioterbium in 1.

Current Advances in PARP1-Targeted Theranostics.

Poly (ADP-ribose) polymerase 1 (PARP1) plays critical roles in DNA repair, chromatin regulation, and cellular equilibrium, positioning it as a pivotal target for therapeutic interventions in cancer and central nervous system (CNS) disorders. PARP1 responds to oxidative stress and DNA damage through PARylation, influencing energy depletion, survival, inflammation, and genomic regulation in many biological scenarios. PARP inhibitors (PARPis) have demonstrated efficacy against cancers harboring defective homologous recombination repair pathways, notably those linked to BRCA mutations.

Measurement of the Ge(d,n)As cross section from 2.1 MeV to 10 MeV.

This work reports experimental Ge(d,n)As cross sections producing Arsenic-71 (t = 65.3 h, 28% β), a potentially useful diagnostic radionuclide. Target stacks containing two Ge foils, a Ni monitor foil, and an Al degrader were irradiated with 5.

Sustainable production of radionuclidically pure antimony-119.

Background: Radiopharmaceutical therapy (RPT) uses radionuclides that decay via one of three therapeutically relevant decay modes (alpha, beta, and internal conversion (IC) / Auger electron (AE) emission) to deliver short range, highly damaging radiation inside of diseased cells, maintaining localized dose distribution and sparing healthy cells. Antimony-119 (Sb, t = 38.19 h, EC = 100%) is one such IC/AE emitting radionuclide, previously limited to in silico computational investigation due to barriers in production, chemical separation, and chelation.

Monte Carlo-Based Nanoscale Dosimetry Holds Promise for Radiopharmaceutical Therapy Involving Auger Electron Emitters.

Radiopharmaceutical therapy (RPT) is evolving as a promising strategy for treating cancer. As interest grows in short-range particles, like Auger electrons, understanding the dose-response relationship at the deoxyribonucleic acid (DNA) level has become essential. In this study, we used the Geant4-DNA toolkit to evaluate DNA damage caused by the Auger-electron-emitting isotope I-125.

Production and radiochemistry of antimony-120m: Efforts toward Auger electron therapy with Sb.

Targeted Meitner-Auger Therapy (TMAT) has potential for personalized treatment thanks to its subcellular dosimetric selectivity, which is distinct from the dosimetry of β and α particle emission based Targeted Radionuclide Therapy (TRT). To date, most clinical and preclinical TMAT studies have used commercially available radionuclides. These studies showed promising results despite using radionuclides with theoretically suboptimal photon to electron ratios, decay kinetics, and electron emission spectra.

Cyclotron production of Sc and Sc from enriched CaO, CaO, and CaO targets.

Sc and Sc are both positron-emitting radioisotopes of scandium with suitable half-lives and favorable positron energies for clinical positron emission tomography (PET) imaging. Irradiation of isotopically enriched calcium targets has higher cross sections compared to titanium targets and higher radionuclidic purity and cross sections than natural calcium targets for reaction routes possible on small cyclotrons capable of accelerating protons and deuterons. In this work, we investigate the following production routes via proton and deuteron bombardment on CaCO and CaO target materials: Ca(d,n)Sc, Ca(p,n)Sc, Ca(d,n)Sc, Ca(p,n)Sc, and Ca(p,2n)Sc.

Copper-Mediated Radiobromination of (Hetero)Aryl Boronic Pinacol Esters.

A copper-mediated radiobromination of (hetero)aryl boronic pinacol esters is described. Cyclotron-produced [Br]bromide was isolated using an anion exchange cartridge, wherein the pre-equilibration and elution solutions played a critical role in downstream deboro-bromination. The bromination tolerates a broad range of functional groups, labeling molecules with ranging electronic and steric effects.

Nanostructured polyvinylpyrrolidone-curcumin conjugates allowed for kidney-targeted treatment of cisplatin induced acute kidney injury.

Acute kidney injury (AKI) leads to unacceptably high mortality due to difficulties in timely intervention and less efficient renal delivery of therapeutic drugs. Here, a series of polyvinylpyrrolidone (PVP)-curcumin nanoparticles (PCurNP) are designed to meet the renal excretion threshold (∼45 kDa), presenting a controllable delivery nanosystem for kidney targeting. Renal accumulation of the relatively small nanoparticles, Zr-PCurNP M10 with the diameter between 5 and 8 nm, is found to be 1.

A High Separation Factor for Er from Ho for Targeted Radionuclide Therapy.

Radionuclides emitting Auger electrons (AEs) with low (0.02-50 keV) energy, short (0.0007-40 µm) range, and high (1-10 keV/µm) linear energy transfer may have an important role in the targeted radionuclide therapy of metastatic and disseminated disease.

Alternative strategies for the synthesis of [C]ER176 for PET imaging of neuroinflammation.

[C]ER176 is a next generation PET radioligand for imaging 18 kDa translocator protein, a biomarker for neuroinflammation. The goal of this work was to investigate alternative strategies for the radiochemical synthesis, purification, and formulation of [C]ER176. An optimized tri-solvent high-performance liquid chromatography (HPLC) protocol is described to separate the hydro-de-chlorinated byproduct from [C]ER176.

A Third Generation Potentially Bifunctional Trithiol Chelate, Its Sb(III) Complex, and Selective Chelation of Radioantimony (Sb) from Its Sn Target.

The therapeutic potential of the Meitner-Auger- and conversion-electron emitting radionuclide Sb remains unexplored because of the difficulty of incorporating it into biologically targeted compounds. To address this challenge, we report the development of Sb production from electroplated tin cyclotron targets and its complexation by a novel trithiol chelate. The chelation reaction occurs in harsh solvent conditions even in the presence of large quantities of tin, which are necessary for production on small, low energy (16 MeV) cyclotrons.

Neurofibrillary tau depositions emerge with subthreshold cerebral beta-amyloidosis in down syndrome.

Introduction: Adults with Down syndrome are genetically predisposed to develop Alzheimer's disease and accumulate beta-amyloid plaques (Aβ) early in life. While Aβ has been heavily studied in Down syndrome, its relationship with neurofibrillary tau is less understood. The aim of this study was to evaluate neurofibrillary tau deposition in individuals with Down syndrome with varying levels of Aβ burden.

Characterization of actinide resin for separation of Mn from bulk target material.

We report an extraction chromatography-based method via Actinide Resin for the isolation of radio-manganese from both natural chromium and isotopically enriched iron targets for cyclotron production of Mn and Mn. For the separation of Mn from nCr, a decay-corrected radiochemical yield of 83.7 ± 8.

Improved production of Br, Br and Br via CoSe cyclotron targets and vertical dry distillation.

Introduction: The radioisotopes of bromine are uniquely suitable radiolabels for small molecule theranostic radiopharmaceuticals but are of limited availability due to production challenges. Significantly improved methods were developed for the production and radiochemical isolation of clinical quality Br, Br, and Br. The radiochemical quality of the radiobromine produced using these methods was tested through the synthesis of a novel Br-labeled inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1), a DNA damage response protein.

Production and in vivo PET/CT imaging of the theranostic pair La.

The present study describes a novel method for the low energy cyclotron production and radiochemical isolation of no-carrier-added La from bulk Ba. This separation strategy combines precipitation and single-column extraction chromatography to afford an overall radiochemical yield (92 ± 2%) and apparent molar activity (22 ± 4 Mbq/nmol) suitable for the radiolabeling of DOTA-conjugated vectors. The produced La has a radiochemical and radionuclidic purity amenable for La/La-based cancer theranostic applications.

Simplified and automatable radiochemical separation strategy for the production of radiopharmaceutical quality Y using single column extraction chromatography.

We present a simplified, automatable single-column radiochemical separation method using the extraction chromatographic branched-DGA resin for the production of no-carrier-added Y with a radiochemical yield higher than 95%, an apparent molar activity of 1.4 ± 0.4 Ci/μmol (DOTA) and 2.

Evaluation of a chloride-based Zr isolation strategy using a tributyl phosphate (TBP)-functionalized extraction resin.

Introduction: The remarkable stability of the Zr-DOTA complex has been shown in recent literature. The formation of this complex appears to require Zr-chloride as the complexation precursor rather than the more conventional Zr-oxalate. In this work we present a method for the direct isolation of Zr-chloride from irradiated Y foils.

Reassembly of Zr-Labeled Cancer Cell Membranes into Multicompartment Membrane-Derived Liposomes for PET-Trackable Tumor-Targeted Theranostics.

Nanoengineering of cell membranes holds great potential to revolutionize tumor-targeted theranostics, owing to their innate biocompatibility and ability to escape from the immune and reticuloendothelial systems. However, tailoring and integrating cell membranes with drug and imaging agents into one versatile nanoparticle are still challenging. Here, multicompartment membrane-derived liposomes (MCLs) are developed by reassembling cancer cell membranes with Tween-80, and are used to conjugate Zr via deferoxamine chelator and load tetrakis(4-carboxyphenyl) porphyrin for in vivo noninvasive quantitative tracing by positron emission tomography imaging and photodynamic therapy (PDT), respectively.

PET radiometals for antibody labeling.

Recent advances in molecular characterization of tumors have made possible the emergence of new types of cancer therapies where traditional cytotoxic drugs and nonspecific chemotherapy can be complemented with targeted molecular therapies. One of the main revolutionary treatments is the use of monoclonal antibodies (mAbs) that selectively target the disseminated tumor cells while sparing normal tissues. mAbs and related therapeutics can be efficiently radiolabeled with a wide range of radionuclides to facilitate preclinical and clinical studies.

Activatable Hybrid Nanotheranostics for Tetramodal Imaging and Synergistic Photothermal/Photodynamic Therapy.

A multifunctional core-satellite nanoconstruct is designed by assembling copper sulfide (CuS) nanoparticles on the surface of [ Zr]-labeled hollow mesoporous silica nanoshells filled with porphyrin molecules, for effective cancer imaging and therapy. The hybrid nanotheranostic demonstrates three significant features: (1) simple and robust construction from biocompatible building blocks, demonstrating prolonged blood retention, enhanced tumor accumulation, and minimal long-term systemic toxicity, (2) rationally selected functional moieties that interact together to enable simultaneous tetramodal (positron emission tomography/fluorescence/Cerenkov luminescence/Cerenkov radiation energy transfer) imaging for rapid and accurate delineation of tumors and multimodal image-guided therapy in vivo, and (3) synergistic interaction between CuS-mediated photothermal therapy and porphyrin-mediated photodynamic therapy which results in complete tumor elimination within a day of treatment with no visible recurrence or side effects. Overall, this proof-of-concept study illustrates an efficient, generalized approach to design high-performance core-satellite nanohybrids that can be easily tailored to combine a wide variety of imaging and therapeutic modalities for improved and personalized cancer theranostics in the future.

Chelator-Free Labeling of Metal Oxide Nanostructures with Zirconium-89 for Positron Emission Tomography Imaging.

Radiolabeling of molecules or nanoparticles to form imaging probes is critical for positron emission tomography (PET) imaging, which, with high sensitivity and the ability for quantitative imaging, has been widely used in the clinic. While conventional radiolabeling often employs chelator molecules, a general method for chelator-free radiolabeling of a wide range of materials remains to be developed. Herein, we determined that 10 different types of metal oxide (MO M = Gd, Ti, Te, Eu, Ta, Er, Y, Yb, Ce, or Mo, x = 1-2, y = 2-5) nanomaterials with polyethylene glycol (PEG) modification could be labeled with Zr, a PET tracer, via a simple yet general chelator-free radiolabeling method upon simple mixing.

Characterization of the radiosynthesis and purification of [F]THK-5351, a PET ligand for neurofibrillary tau.

This work characterizes the radiochemical synthesis, purification, and formulation of [F]THK-5351, a tau PET radioligand, and develops an automated radiosynthesis routine (ELIXYS, Sofie Biosciences). Nucleophilic radiofluorination reaction was complete by 7min at 110°C with radiochemical yields proportional to precursor mass (0.1-0.

Zr-labeled nivolumab for imaging of T-cell infiltration in a humanized murine model of lung cancer.

Purpose: Nivolumab is a human monoclonal antibody specific for programmed cell death-1 (PD-1), a negative regulator of T-cell activation and response. Acting as an immune checkpoint inhibitor, nivolumab binds to PD-1 expressed on the surface of many immune cells and prevents ligation by its natural ligands. Nivolumab is only effective in a subset of patients, and there is limited evidence supporting its use for diagnostic, monitoring, or stratification purposes.