Preclinical Evaluation of Ac as a Theranostic Agent: Imaging, Dosimetry, and Therapy.

Ac (t = 29.37 h) has been proposed as a theranostic radioisotope leveraging both its diagnostic γ-emissions and therapeutic α-emissions. Ac emits 158 and 230 keV γ-photons ideal for quantitative SPECT imaging and acts as an in vivo generator of 4 high-energy α-particles.

Quantitative SPECT imaging of Tb and Tb for preclinical theranostic radiopharmaceutical development.

Background: Element-equivalent matched theranostic pairs facilitate quantitative in vivo imaging to establish pharmacokinetics and dosimetry estimates in the development of preclinical radiopharmaceuticals. Terbium radionuclides have significant potential as matched theranostic pairs for multipurpose applications in nuclear medicine. In particular, Tb (t = 5.

quantitative SPECT imaging of actinium-226: feasibility and proof-of-concept.

.Ac radiopharmaceuticals have tremendous potential for targeted alpha therapy, however,Ac (= 9.9 d) lacks direct gamma emissions forimaging.

Preclinical evaluation of MC1R targeting theranostic pair [Tb]Tb-crown-αMSH and [Tb]Tb-crown-αMSH.

Background: Targeted radionuclide therapy is established as a highly effective strategy for the treatment of metastatic tumors; however, the co-development of suitable imaging companions to therapy remains significant challenge. Theranostic isotopes of terbium (Tb, Tb, Tb, Tb) have the potential to provide chemically identical radionuclidic pairs, which collectively encompass all modes of nuclear decay relevant to nuclear medicine. Herein, we report the first radiochemistry and preclinical studies involving Tb- and Tb-labeled crown-αMSH, a small peptide-based bioconjugate suitable for targeting melanoma.

Rearmed Bifunctional Chelating Ligand for Ac/Tb Precision-Guided Theranostic Radiopharmaceuticals─HnoneunpaX.

Superior bifunctional chelating ligands, which can sequester both α-emitting radionuclides (Ac, Bi) and their diagnostic companions (Tb, In), remain a formidable challenge to translating targeted alpha therapy, with complementary diagnostic imaging, to the clinic. HnoneupaX, a chelating ligand with an unusual diametrically opposed arrangement of pendant donor groups, has been developed to this end. HnoneunpaX preferentially complexes Ln and An ions, forming thermodynamically stable (pLa = 17.

Preclinical Evaluation of [Tb]Tb-Crown-TATE-A Novel SPECT Imaging Theranostic Agent Targeting Neuroendocrine Tumours.

Terbium radioisotopes (Tb, Tb, Tb, Tb) offer a unique class of radionuclides which encompass all four medicinally relevant nuclear decay modalities (α, , γ, /e), and show high potential for the development of element-matched theranostic radiopharmaceuticals. The goal of this study was to design, synthesise, and evaluate the suitability of crown-TATE as a new peptide-conjugate for radiolabelling of [Tb]Tb and [Tb]Tb, and to assess the imaging and pharmacokinetic properties of each radiotracer in tumour-bearing mice. [Tb]Tb-crown-TATE and [Tb]Tb-crown-TATE were prepared efficiently under mild conditions, and exhibited excellent stability in human serum (>99.

Comparative Study of a Decadentate Acyclic Chelate, HOPO-O, and Its Octadentate Analogue, HOPO-O, for Radiopharmaceutical Applications.

Radiolanthanides and actinides are aptly suited for the diagnosis and treatment of cancer via nuclear medicine because they possess unique chemical and physical properties (e.g., radioactive decay emissions).

SPECT imaging ofAc as a theranostic isotope forAc radiopharmaceutical development.

. The development of alpha-emitting radiopharmaceuticals usingAc ( = 9.92 d) benefits from the quantitative determination of its biodistribution and is not always easy to directly measure.

Potential for production of medical radionuclides with on-line isotope separation at the ISAC facility at TRIUMF and particular discussion of the examples of Er and Tb.

Production of medical radionuclides with ISOL facilities is a unique production method that may provide access to preclinical quantities of some rare and potent radionuclides for nuclear medicine. Particularly attention over the past years was focused on several promising candidates for Targeted Radionuclides Therapy (TRT). With this review, we provide some perspectives of using the TRIUMF ISOL facility (ISAC) to produce medical radionuclides for TRT application and highlight our current effort to collect of Er and Tb for Auger Therapy and SPECT imaging, respectively.

Evaluation of polydentate picolinic acid chelating ligands and an α-melanocyte-stimulating hormone derivative for targeted alpha therapy using ISOL-produced Ac.

Background: Actinium-225 (Ac, t = 9.9 d) is a promising candidate radionuclide for use in targeted alpha therapy (TAT), though the currently limited global supply has hindered the development of a suitable Ac-chelating ligand and Ac-radiopharmaceuticals towards the clinic. We at TRIUMF have leveraged our Isotope Separation On-Line (ISOL) facility to produce Ac and use the resulting radioactivity to screen a number of potential Ac-radiopharmaceutical compounds.

Multi-isotope SPECT imaging of the Ac decay chain: feasibility studies.

Effective use of the [Formula: see text] decay chain in targeted internal radioimmunotherapy requires the retention of both [Formula: see text] and progeny isotopes at the target site. Imaging-based pharmacokinetic tests of these pharmaceuticals must therefore separately yet simultaneously image multiple isotopes that may not be colocalized despite being part of the same decay chain. This work presents feasibility studies demonstrating the ability of a microSPECT/CT scanner equipped with a high energy collimator to simultaneously image two components of the [Formula: see text] decay chain: [Formula: see text] (218 keV) and [Formula: see text] (440 keV).

Development of a preclinical Rn/At generator system for targeted alpha therapy research with At.

Introduction: The availability of At for targeted alpha therapy research can be increased by the Rn/At generator system, whereby At is produced by Rn electron capture decay. This study demonstrated the feasibility of using generator-produced At to label monoclonal antibody (BC8, anti-human CD45) for preclinical use, following isolation from the Po contamination also produced by these generators (by Rn α-decay).

Methods: Rn was produced by Fr electron capture decay following mass separated ion beam implantation and chemically isolated in liquid alkane hydrocarbon (dodecane).

Rn/At and At production with intense mass separated Fr ion beams for preclinical At-based α-therapy research.

Mass-separated francium beams (Fr or Fr) were implanted into solid targets for producing Rn (14.6h half-life) or At (5.41h), in situ.

CO-releasing molecule (CORM) conjugate systems.

The development of CORMs (CO-releasing molecules) as a prodrug for CO administration in living organisms has attracted significant attention. CORMs offer the promising possibility of a safe and controllable release of CO in low amounts triggered by light, ligands, enzymes, etc. For the targeting of specific tissues or diseases and to prevent possible side effects from metals and other residues after CO release, these CORMs are attached to biocompatible systems, like peptides, polymers, nanoparticles, dendrimers, protein cages, non-wovens, tablets, and metal-organic frameworks.

Atom-at-a-time laser resonance ionization spectroscopy of nobelium.

Optical spectroscopy of a primordial isotope has traditionally formed the basis for understanding the atomic structure of an element. Such studies have been conducted for most elements and theoretical modelling can be performed to high precision, taking into account relativistic effects that scale approximately as the square of the atomic number. However, for the transfermium elements (those with atomic numbers greater than 100), the atomic structure is experimentally unknown.

Synthesis of oxime-based CO-releasing molecules, CORMs and their immobilization on maghemite nanoparticles for magnetic-field induced CO release.

Oxime-based CO-releasing molecules (oximeCORMs) were immobilized with a catechol-modified backbone on maghemite iron oxide nanoparticles (IONPs) to give oximeCORM@IONP. The CO release from the free and immobilized oximeCORMs was measured using the standard myoglobin assay. The oximeCORM-nanoparticles were coated with dextran for improved water solubility and confined into an alginate shell for protection and separation from the surrounding myoglobin assay to allow for CO release studies by UV/Vis absorption without interference from highly-absorptive oximeCORM@IONP.

Stabilizing Alginate Confinement and Polymer Coating of CO-Releasing Molecules Supported on Iron Oxide Nanoparticles To Trigger the CO Release by Magnetic Heating.

Maghemite (Fe2O3) iron oxide nanoparticles (IONPs) were synthesized, modified with covalent surface-bound CO-releasing molecules of a tri(carbonyl)-chlorido-phenylalaninato-ruthenium(II) complex (CORM), and coated with a dextran polymer. The time- and temperature-dependent CO release from this CORM-3 analogue was followed by a myoglobin assay. A new measurement method for the myoglobin assay was developed, based on confining "water-soluble" polymer-coated Dextran500k@CORM@IONP particles in hollow spheres of nontoxic and easily prepared calcium alginate.

Nuclear and in-source laser spectroscopy with the ISAC yield station.

A new decay station has been built for the ISAC facility at TRIUMF for the rapid and reliable characterization of radioactive ion beam (RIB) compositions and intensities with the capability of simultaneously collecting α, β, and γ decay data from RIB with intensities between a few and ≈10(11) ions per second. It features user-friendly control, data acquisition, and analysis software. The analysis of individual decay time structures allows the unambiguous assignment of α and γ lines even with substantial isobaric contamination present.

An ion guide laser ion source for isobar-suppressed rare isotope beams.

Modern experiments at isotope separator on-line (ISOL) facilities like ISAC at TRIUMF often depend critically on the purity of the delivered rare isotope beams. Therefore, highly selective ion sources are essential. This article presents the development and successful on-line operation of an ion guide laser ion source (IG-LIS) for the production of ion beams free of isobaric contamination.

Metal carbonyls supported on iron oxide nanoparticles to trigger the CO-gasotransmitter release by magnetic heating.

Magnetic iron oxide, maghemite (Fe2O3) nanoparticles with covalent surface-bound CO-releasing molecules (CORMs) can be triggered to release CO through heating in an alternating magnetic field. In the proof-of-concept study the rate of CO-release from [RuCl(CO3)(μ-DOPA)]@maghemite nanoparticles was doubled upon exposure to an external alternating magnetic field (31.7 kAm(-1), 247 kHz, 25 °C, 39.

Tricarbonyl[tris(1-methyl-1H-imidazol-2-yl-κN(3))methanol]manganese(I) trifluoromethanesulfonate.

In the title compound, [Mn(C(13)H(16)N(6)O)(CO)(3)](CF(3)O(3)S), the Mn(I) atom has a slightly distorted octa-hedral geometry. The three CO ligands have C-Mn-C angles in the range 89.44 (10)-92.

(Picolinato-κN,O)[tris(2-isopropyl-1H-imidazol-4-yl-κN)phosphane]cobalt(II) nitrate.

Single crystals of the title compound, [Co(C(6)H(4)NO(2))(C(18)H(27)N(6)P)]NO(3), were obtained from the reaction of nitrato[tris-(2-isopropyl-imidazol-4-yl)phosphane]cobalt(II) nitrate with picolinic acid in the presence of potassium tert-butoxide as base. The coordination polyhedron around the central Co(II) ion is about halfway between square-pyramidal and trigonal-bipyramidal geometry. In the structure, the nitrate counter-anion is connected by N-H⋯O hydrogen bonding to the complex cation.

Stabilisation of water-soluble platinum nanoparticles by phosphonic acid derivatives.

Sodium 2-(diphenylphosphino)ethyl phosphonate (1) was investigated as a stabilising agent for platinum nanoparticles (Pt-NPs) in aqueous solution. This phosphino phosphonate is known to stabilise rhodium nanoparticles (NPs) in water. Here we report that in the case of Pt-NPs this ligand is indirectly involved in the stabilisation mechanism and the actual stabilisation agent is the platinum complex Na(2)[Pt(1)(2)] (2).

Ovarian activity in Fleckvieh, Brown Swiss and two strains of Holstein-Friesian cows in pasture-based, seasonal calving dairy systems.

The objectives of the study were to compare the ovarian activity of Holstein-Friesian (CH HF), Fleckvieh (CH FV) and Brown Swiss (CH BS) dairy cows of Swiss origin with that of Holstein-Friesian (NZ HF) dairy cows of New Zealand origin, the latter being used as a reference for reproductive performance in pasture-based seasonal calving systems. Fifty, second-lactation NZ HF cows were each paired with a second-lactation Swiss cow (17, 15 and 18 CH HF, CH FV and CH BS respectively) in 13 pasture-based, seasonal-calving commercial dairy farms in Switzerland. Ovarian activity was monitored by progesterone profiling from calving to first breeding service.

Gold(I) complexes of water-soluble diphos-type ligands: synthesis, anticancer activity, apoptosis and thioredoxin reductase inhibition.

Gold(I) complexes of imidazole and thiazole-based diphos type ligands were prepared and their potential as chemotherapeutics investigated. Depending on the ligands employed and the reaction conditions complexes [L(AuCl)(2)] and [L(2)Au]X (X = Cl, PF(6)) are obtained. The ligands used are diphosphanes with azoyl substituents R(2)P(CH(2))(2)PR(2) {R = 1-methylimidazol-2-yl (1), 1-methylbenzimidazol-2-yl (4), thiazol-2-yl (5) and benzthiazol-2-yl (6)} as well as the novel ligands RPhP(CH(2))(2)PRPh {R = 1-methylimidazol-2-yl (3)} and R(2)P(CH(2))(3)PR(2) {R = 1-methylimidazol-2-yl (2)}.