Optimized chelator and nanoparticle strategies for high-activity Pd-loaded biodegradable brachytherapy seeds.

Background: Brachytherapy (BT) is routinely used in the treatment of various cancers. Current BT relies on the placement of large sources of radioactivity at the tumor site, requiring applicators that may cause local traumas and lesions. Further, they suffer from inflexibility in where they can be placed and some sources reside permanently in the body, causing potential long-term discomfort.

Novel radionuclides: demand, production and distribution for translational research in Europe.

Background: In the field of medical and scientific research, radionuclides are used to investigate various physiological and pathological processes. PRISMAP - the European medical radionuclide programme was created to bring together production facilities including intense neutron sources, an isotope mass separation facility, high-power accelerators, biomedical research institutes, and hospitals to support medical research. The aim of this article is to introduce readers with the current status of innovative radionuclides in Europe.

Production of Cu at a biomedical cyclotron via Zn(p,α)Cu reaction and its evaluation in a preclinical study using small animal SPECT/CT.

Clinical advancements in nuclear medicine theranostics has excited a research interest in exploring novel radionuclides for medical use. The duo of the β emitter Cu and the positron emitter Cu, has advantages over the well-established clinical pair Ga and Lu in terms of capability for high-precision therapy. Low availability has hindered the use of Cu whereas Cu has become established at a limited number of sites through production in low-to-medium energy biomedical cyclotrons.

Novel radionuclides for use in Nuclear Medicine in Europe: where do we stand and where do we go?

Background: In order to support the ongoing research across Europe to facilitate access to novel radionuclides, the PRISMAP consortium (European medical radionuclides programme) was established to offer the broadest catalog of non-conventional radionuclides for medical and translational research. The aim of this article is to introduce readers with current status of novel radionuclides in Europe.

Main Body: A consortium questionnaire was disseminated through the PRISMAP consortium and user community, professional associations and preclinical/clinical end users in Europe and the current status of clinical end-users in nuclear medicine were identified.

Tuning the Framework of Thioether-Functionalized Polyazamacrocycles: Searching for a Chelator for Theranostic Silver Radioisotopes.

Silver-111 is an attractive unconventional candidate for targeted cancer therapy as well as for single photon emission computed tomography and can be complemented by silver-103 for positron emission tomography noninvasive diagnostic procedures. However, the shortage of chelating agents capable of forming stable complexes tethered to tumor-seeking vectors has hindered their application so far. In this study, a comparative investigation of a series of sulfur-containing structural homologues, namely, 1,4,7-tris[2-(methylsulfanyl)ethyl)]-1,4,7-triazacyclononane (NO3S), 1,5,9-tris[2-(methylsulfanyl)ethyl]-1,5,9-triazacyclododecane (TACD3S), 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclotridecane (TRI4S), and 1,4,8,11-tetrakis[2-(methylsulfanyl)ethyl]-1,4,8,11-tetraazacyclotetradecane (TE4S) was conducted to appraise the influence of different polyazamacrocyclic backbones on Ag complexation.

Improved procedures for production and purification of La from enriched [Ba]BaCO on a 16.5 MeV cyclotron.

Lanthanum-135 (La) is a favorable Auger electron emitter with a high Auger electron yield and low gamma emission, making it promising for Auger electron radiotherapy. However, successful application requires reliable and scalable La production. Up to now, metallic natural barium (Ba) is a commonly used target material, but this material is sensitive to moisture and oxidation.

Towards in vivo applications of Ag perturbed angular correlation of γ-rays (PAC) spectroscopy.

Ag-perturbed angular correlation of γ-rays (PAC) spectroscopy provides information on the nuclear quadrupole interactions, and thereby on the local structure and dynamics of the silver ion binding site. Brownian rotational motion, i.e.

Tying Up a Loose End: On the Role of the C-Terminal CCHHRAG Fragment of the Metalloregulator CueR.

The transcriptional regulator CueR is activated by the binding of Cu , Ag , or Au to two cysteinates in a near-linear fashion. The C-terminal CCHHRAG sequence in Escherichia coli CueR present potential additional metal binding ligands and here we explore the effect of deleting this fragment on the binding of Ag to CueR. CD spectroscopic and ESI-MS data indicate that the high Ag -binding affinity of WT-CueR is significantly reduced in Δ7C-CueR.

Multi-curie production of gallium-68 on a biomedical cyclotron and automated radiolabelling of PSMA-11 and DOTATATE.

Background: With increasing clinical demand for gallium-68, commercial germanium-68/gallium-68 ([Ge]Ge/[Ga]Ga) generators are incapable of supplying sufficient amounts of the short-lived daughter isotope. In this study, we demonstrate a high-yield, automated method for producing multi-Curie levels of [Ga]GaCl from solid zinc-68 targets and subsequent labelling to produce clinical-grade [Ga]Ga-PSMA-11 and [Ga]Ga-DOTATATE.

Results: Enriched zinc-68 targets were irradiated at up to 80 µA with 13 MeV protons for 120 min; repeatedly producing up to 194 GBq (5.

Highly Stable Silver(I) Complexes with Cyclen-Based Ligands Bearing Sulfide Arms: A Step Toward Silver-111 Labeled Radiopharmaceuticals.

With a half-life of 7.45 days, silver-111 (β 1.04 MeV, 245.

Cs-131 as an experimental tool for the investigation and quantification of the radiotoxicity of intracellular Auger decays in vitro.

Purpose: In this work, we set out to provide an experimental setup, using Cs-131, with associated dosimetry for studying relative biological effectiveness (RBE) of Auger emitters.

Material And Methods: Cs-131 decays by 100% electron capture producing K- (9%) and L- (80%) Auger electrons with mean energies of 26 keV and 3.5 keV, respectively, plus ≈ 9.

A solid support generator of the Auger electron emitter rhodium-103m from [Pd]palladium.

Auger electron therapy is an attractive modality for targeting microscopic tumors. Rhodium-103 m (Rh, T = 56.1 min) is a promising Auger electron emitter that can be obtained as the decay product of palladium-103 (Pd, T = 16.

Flexibility of the CueR Metal Site Probed by Instantaneous Change of Element and Oxidation State from Ag to Cd.

Selectivity for monovalent metal ions is an important facet of the function of the metalloregulatory protein CueR. Ag perturbed angular correlation of γ-rays (PAC) spectroscopy probes the metal site structure and the relaxation accompanying the instantaneous change from Ag to Cd upon Ag radioactive decay. That is, a change from Ag , which activates transcription, to Cd , which does not.

Cell colony counter called CoCoNut.

Clonogenic assays are powerful tools for testing cell reproductive death after biological damage caused by, for example, ionizing radiation. Traditionally, the methods require a cumbersome, slow and eye-straining manual counting of viable colonies under a microscope. To speed up the counting process and minimize those issues related to the subjective decisions of the scoring personnel, we developed a semi-automated, image-based cell colony counting setup, named CoCoNut (Colony Counter developed by the Nutech department at the Technical University of Denmark).

Evolution of the Biosynthetic Pathway for Cyanogenic Glucosides in Lepidoptera.

Cyanogenic glucosides are widespread defence compounds in plants, and they are also found in some arthropods, especially within Lepidoptera. The aliphatic linamarin and lotaustralin are the most common cyanogenic glucosides in Lepidoptera, and they are biosynthesised de novo, and/or sequestered from food plants. Their biosynthetic pathway was elucidated in the burnet moth, Zygaena filipendulae, and consists of three enzymes: two cytochrome P450 enzymes, CYP405A2 and CYP332A3, and a glucosyl transferase, UGT33A1.

Structure of Radical-Induced Cell Death1 Hub Domain Reveals a Common αα-Scaffold for Disorder in Transcriptional Networks.

Communication within cells relies on a few protein nodes called hubs, which organize vast interactomes with many partners. Frequently, hub proteins are intrinsically disordered conferring multi-specificity and dynamic communication. Conversely, folded hub proteins may organize networks using disordered partners.

Radiobiological effects of tritiated water short-term exposure on V79 clonogenic cell survival.

Purpose: We set out to improve the accuracy of absorbed dose calculations for in vitro measurements of the relative biological effectiveness (RBE) of tritiated water (HTO) for the clonogenic cell survival assay, also considering the influence of the end-of-track linear energy transfer (LET) of low-energy electrons.

Materials And Methods: The COmputation Of Local Electron Release (COOLER) program was adopted to investigate the cell geometry and the tritium full beta-decay spectrum impact on the S-values and subsequently on the RBE of HTO for clonogenic cell survival at similar high dose rates (HDR).

Results: S-values for cells growing in suspension are usually comparable to those for adherent cells.

Towards Translational ImmunoPET/MR Imaging of Invasive Pulmonary Aspergillosis: The Humanised Monoclonal Antibody JF5 Detects Lung Infections .

Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of hematological malignancy or bone marrow transplant patients caused by the ubiquitous environmental fungus . Current diagnostic tests for the disease lack sensitivity as well as specificity, and culture of the fungus from invasive lung biopsy, considered the gold standard for IPA detection, is slow and often not possible in critically ill patients. In a previous study, we reported the development of a novel non-invasive procedure for IPA diagnosis based on antibody-guided positron emission tomography and magnetic resonance imaging (immunoPET/MRI) using a [Cu]DOTA-labeled mouse monoclonal antibody (mAb), mJF5, specific to .

Spatial separation of the cyanogenic β-glucosidase ZfBGD2 and cyanogenic glucosides in the haemolymph of larvae facilitates cyanide release.

Low molecular weight compounds are typically used by insects and plants for defence against predators. They are often stored as inactive β-glucosides and kept separate from activating β-glucosidases. When the two components are mixed, the β-glucosides are hydrolysed releasing toxic aglucones.

The COOLER Code: A Novel Analytical Approach to Calculate Subcellular Energy Deposition by Internal Electron Emitters.

COmputation Of Local Electron Release (COOLER), a software program has been designed for dosimetry assessment at the cellular/subcellular scale, with a given distribution of administered low-energy electron-emitting radionuclides in cellular compartments, which remains a critical step in risk/benefit analysis for advancements in internal radiotherapy. The software is intended to overcome the main limitations of the medical internal radiation dose (MIRD) formalism for calculations of cellular S-values (i.e.

Experimental implementation and proof of principle for a radionuclidic purity test solely based on half-life measurement.

In this paper we present the results of an experimental implementation of the method (Jørgensen et al., 2012) for testing the radionuclidic purity (RNP) of F-18 compounds. The overall limitations of the experimental methods and their possible impacts on RNP detectability have been identified.

PET/CT Based In Vivo Evaluation of 64Cu Labelled Nanodiscs in Tumor Bearing Mice.

64Cu radiolabelled nanodiscs based on the 11 α-helix MSP1E3D1 protein and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine lipids were, for the first time, followed in vivo by positron emission tomography for evaluating the biodistribution of nanodiscs. A cancer tumor bearing mouse model was used for the investigations, and it was found that the approximately 13 nm nanodiscs, due to their size, permeate deeply into cancer tissue. This makes them promising candidates for both drug delivery purposes and as advanced imaging agents.

Improved methods to determine radionuclidic purity of F-18 compounds.

Current revisions of monographs for F-18 pharmaceuticals in the European Pharmacopoeia (Ph. Eur.) (Ph.

Light-induced copper(II) coordination by a bicyclic tetraaza chelator through a ligand-to-metal charge-transfer reaction.

To enable utilization of the broad potential of copper isotopes in nuclear medicine, rapid and robust chelation of the copper is required. Bowl adamanzanes (bicyclic tetraaza ligands) can form kinetically stable copper complexes, but they are usually formed at low rates unless high pH values and high temperatures are applied. We have investigated the effects of the variation in the pH, different anions, and UV irradiation on the chelation rate.

A new and simple calibration-independent method for measuring the beam energy of a cyclotron.

This work recommends a new and simple-to-perform method for measuring the beam energy of an accelerator. The proposed method requires the irradiation of two monitor foils interspaced by an energy degrader. The primary advantage of the proposed method, which makes this method unique from previous energy evaluation strategies that employ the use of monitor foils, is that this method is independent of the detector efficiency calibration.