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.

Intermetallic cobalt-gallium targets for production of germanium radioisotopes.

Increasing interest in targeted radionuclide therapy motivates the development of new radionuclides. The unique emission spectrum from Ge make it an ideal candidate for probing microdosimetric effects of low energy electrons absent confounding photon dose. This work reports a novel intermetallic target of Co and Ga for accelerator production of no-carrier-added Ge and a new method to isolate the Ge in high yields and purities.

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.

Crosstalk between Microglia and Neurons in Neurotrauma: An Overview of the Underlying Mechanisms.

Microglia are the resident immune cells of the brain and play a crucial role in housekeeping and maintaining homeostasis of the brain microenvironment. Upon injury or disease, microglial cells become activated, at least partly, via signals initiated by injured neurons. Activated microglia, thereby, contribute to both neuroprotection and neuroinflammation.

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.

PET Measures of D1, D2, and DAT Binding Are Associated With Heightened Tactile Responsivity in Rhesus Macaques: Implications for Sensory Processing Disorder.

Sensory processing disorder (SPD), a developmental regulatory condition characterized by marked under- or over-responsivity to non-noxious sensory stimulation, is a common but poorly understood disorder that can profoundly affect mood, cognition, social behavior and adaptive life skills. Little is known about the etiology and neural underpinnings. Clinical research indicates that children with SPD show greater prevalence of difficulties in complex cognitive behavior including working memory, behavioral flexibility, and regulation of sensory and affective functions, which are related to prefrontal cortex (PFC), striatal, and midbrain regions.

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.

In vivo imaging of inflammation and oxidative stress in a nonhuman primate model of cardiac sympathetic neurodegeneration.

Loss of cardiac postganglionic sympathetic innervation is a characteristic pathology of Parkinson's disease (PD). It progresses over time independently of motor symptoms and is not responsive to typical anti-parkinsonian therapies. Cardiac sympathetic neurodegeneration can be mimicked in animals using systemic dosing of the neurotoxin 6-hydroxydopamine (6-OHDA).

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.

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.

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.

Cyclotron production and radiochemical separation of Co and Co from Fe, Ni and Fe targets.

This work presents the production with a cyclotron of the positron emitter Co via the Fe(d,n) and Ni(p,α) reactions and the Auger electron emitter Co via the Fe(d,n) reaction after high current (40μA p and 60μA d) irradiation on electroplated targets. High specific activity radionuclides (up to 55.6 GBq/μmol Co and 31.

Half-life of Mn.

The half-life of Mn was measured by serial gamma spectrometry of the 511-keV annihilation photon following decay by emission. Data were collected every 100 seconds for 100,000-230,000 seconds within each measurement ( = 4). The 511-keV incidence rate was calculated from the 511-keV spectral peak area and count duration, corrected for detector dead time and radioactive decay.

Preparation and in vivo characterization of MnCl as PET tracer of Ca channel-mediated transport.

Manganese has long been employed as a T-shortening agent in magnetic resonance imaging (MRI) applications, but these techniques are limited by the biotoxicity of bulk-manganese. Positron emission tomography (PET) offers superior contrast sensitivity compared with MRI, and recent preclinical PET studies employing Mn (t: 5.6 d, β: 29%) show promise for a variety of applications including cell tracking, neural tract tracing, immunoPET, and functional β-cell mass quantification.

Radiomanganese PET Detects Changes in Functional β-Cell Mass in Mouse Models of Diabetes.

The noninvasive measurement of functional β-cell mass would be clinically valuable for monitoring the progression of type 1 and type 2 diabetes as well as the viability of transplanted insulin-producing cells. Although previous work using MRI has shown promise for functional β-cell mass determination through voltage-dependent Ca channel (VDCC)-mediated internalization of Mn, the clinical utility of this technique is limited by the cytotoxic levels of the Mn contrast agent. Here, we show that positron emission tomography (PET) is advantageous for determining functional β-cell mass using Mn (: 5.

ImmunoPET Imaging of CTLA-4 Expression in Mouse Models of Non-small Cell Lung Cancer.

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is expressed on the surface of activated T cells and some tumor cells, and is the target of the clinically approved monoclonal antibody ipilimumab. In this study, we investigate specific binding of radiolabeled ipilimumab to CTLA-4 expressed by human non-small cell lung cancer cells in vivo using positron emission tomography (PET). Ipilimumab was radiolabeled with Cu (t = 12.

ImmunoPET and Near-Infrared Fluorescence Imaging of Pancreatic Cancer with a Dual-Labeled Bispecific Antibody Fragment.

Dual-targeted imaging agents have shown improved targeting efficiencies in comparison to single-targeted entities. The purpose of this study was to quantitatively assess the tumor accumulation of a dual-labeled heterobifunctional imaging agent, targeting two overexpressed biomarkers in pancreatic cancer, using positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging modalities. A bispecific immunoconjugate (heterodimer) of CD105 and tissue factor (TF) Fab' antibody fragments was developed using click chemistry.

Radiolabeled pertuzumab for imaging of human epidermal growth factor receptor 2 expression in ovarian cancer.

Purpose: Human epidermal growth factor receptor 2 (HER2) is over-expressed in over 30% of ovarian cancer cases, playing an essential role in tumorigenesis and metastasis. Non-invasive imaging of HER2 is of great interest for physicians as a mean to better detect and monitor the progression of ovarian cancer. In this study, HER2 was assessed as a biomarker for ovarian cancer imaging using Cu-labeled pertuzumab for immunoPET imaging.

Surfactant-stripped naphthalocyanines for multimodal tumor theranostics with upconversion guidance cream.

Surfactant-stripped, nanoformulated naphthalocyanines (nanonaps) can be formed with Pluronic F127 and low temperature membrane processing, resulting in dispersed frozen micelles with extreme contrast in the near infrared region. Here, we demonstrate that nanonaps can be used for multifunctional cancer theranostics. This includes lymphatic mapping and whole tumor photoacoustic imaging following intradermal or intravenous injection in rodents.

Nuclear excitation functions of proton-induced reactions (E = 35 - 90 MeV) from Fe, Cu, and Al.

Fe, Cu, and Al stacked foils were irradiated by 90 MeV protons at the Los Alamos Neutron Science Center's Isotope Production Facility to measure nuclear cross sections for the production of medically relevant isotopes, such as Mn, Mn, Cr, Co, Co and Ni. The decay of radioactive isotopes produced during irradiation was monitored using high-purity germanium gamma spectroscopy over the months following irradiation. Proton fluence was determined using the Al(p,x)Na, Cu(p,x)Zn Cu(p,x)Zn, and Cu(p,x)Co monitor reactions.

Chelator-Free Radiolabeling of Nanographene: Breaking the Stereotype of Chelation.

Macrocyclic chelators have been widely employed in the realm of nanoparticle-based positron emission tomography (PET) imaging, whereas its accuracy remains questionable. Here, we found that Cu can be intrinsically labeled onto nanographene based on interactions between Cu and the π electrons of graphene without the need of chelator conjugation, providing a promising alternative radiolabeling approach that maintains the native in vivo pharmacokinetics of the nanoparticles. Due to abundant π bonds, reduced graphene oxide (RGO) exhibited significantly higher labeling efficiency in comparison with graphene oxide (GO) and exhibited excellent radiostability in vivo.

Intrinsic and Stable Conjugation of Thiolated Mesoporous Silica Nanoparticles with Radioarsenic.

The development of new image-guided drug delivery tools to improve the therapeutic efficacy of chemotherapeutics remains an important goal in nanomedicine. Using labeling strategies that involve radioelements that have theranostic pairs of diagnostic positron-emitting isotopes and therapeutic electron-emitting isotopes has promise in achieving this goal and further enhancing drug performance through radiotherapeutic effects. The isotopes of radioarsenic offer such theranostic potential and would allow for the use of positron emission tomography (PET) for image-guided drug delivery studies of the arsenic-based chemotherapeutic arsenic trioxide (ATO).

Spot-welding solid targets for high current cyclotron irradiation.

Zirconium-89 finds broad application for use in positron emission tomography. Its cyclotron production has been limited by the heat transfer from yttrium targets at high beam currents. A spot welding technique allows a three-fold increase in beam current, without affecting Zr quality.

Uptake and retention of manganese contrast agents for PET and MRI in the rodent brain.

Manganese-enhanced magnetic resonance imaging (MRI) is an established neuroimaging method for signal enhancement, tract tracing, and functional studies in rodents. Along with the increasing availability of combined positron emission tomography (PET) and MRI scanners, the recent development of the positron-emitting isotope Mn has prompted interest in the use of Mn as a dual-modality contrast agent. In this work, we characterized and compared the uptake of systemically delivered Mn and radioactive Mn in the rat brain for MRI and PET, respectively.