A5009576211- Radiopharmaceutical Chemistry and Applications
- Medical Imaging Techniques and Applications
- Medical Imaging and Pathology Studies
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Radioactive element chemistry and processing
- Nuclear Physics and Applications
- Radioactive Decay and Measurement Techniques
- Radiation Therapy and Dosimetry
- Boron Compounds in Chemistry
- Lanthanide and Transition Metal Complexes
- Chemical Synthesis and Characterization
- Particle accelerators and beam dynamics
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- Chemical Reactions and Isotopes
- Lung Cancer Treatments and Mutations
- Radiation Detection and Scintillator Technologies
- Electron and X-Ray Spectroscopy Techniques
- Muon and positron interactions and applications
- Inorganic Fluorides and Related Compounds
- Fusion materials and technologies
- Advanced Chemical Physics Studies
- Neuroblastoma Research and Treatments
- Analytical chemistry methods development
TRIUMF
2017-2025
University of British Columbia
2019-2025
Los Alamos National Laboratory
2014-2018
Johannes Gutenberg University Mainz
2010-2018
Joint Institute for Nuclear Research
2011-2015
Abstract The 18‐membered macrocycle H 2 macropa was investigated for 225 Ac chelation in targeted alpha therapy (TAT). Radiolabeling studies showed that macropa, at submicromolar concentration, complexed all (26 kBq) 5 min RT. [ Ac(macropa)] + remained intact over 7 to 8 days when challenged with either excess La 3+ ions or human serum, and did not accumulate any organ after h healthy mice. A bifunctional analogue, macropa‐NCS, conjugated trastuzumab as well the prostate‐specific membrane...
Abstract Background In the past years, there has been a notable increase in interest regarding targeted alpha therapy using Ac-225, driven by observed promising clinical anti-tumor effects. As production and technology advanced, availability of Ac-225 is expected to near future, making treatment available patients worldwide. Main body can be labelled different biological vectors, whereby success developing radiopharmaceutical depends heavily on labelling conditions, purity radionuclide...
Recent clinical results have demonstrated remarkable treatment responses of late-stage cancer patients when treated with alpha-emitting radionuclides such as actinium-225 (225Ac). The resulting intense global effort to produce greater quantities 225Ac has triggered a number emerging technologies this rare, yet important, radionuclide. Accelerator-based methods for increasing production capacity focused on the high energy (>100 MeV) proton irradiation thorium, despite coproduction undesirable...
Abstract Targeted alpha‐therapy (TAT) has great potential for treating a broad range of late‐stage cancers by delivering focused and lethal radiation dose to tumors. Actinium‐225 ( 225 Ac) is an emerging alpha emitter suitable TAT; however, the availability chelators Ac remains limited small number examples (DOTA macropa). Herein, we report new macrocyclic chelator named ‘ crown’ , which binds quantitatively rapidly (<10 min) at ambient temperature. We synthesized Ac‐ crown ‐αMSH, peptide...
Herein, we present the syntheses and characterization of a new undecadendate chelator, H4py4pa, its bifunctional analog H4py4pa-phenyl-NCS, conjugated to monoclonal antibody, Trastuzumab, which targets HER2+ cancer. H4py4pa possesses excellent affinity for 225Ac (α, t1/2 = 9.92 d) targeted alpha therapy (TAT), where quantitative radiolabeling yield was achieved at ambient temperature, pH 7, in 30 min 10–6 M chelator concentration, leading complex highly stable mouse serum least 9 d. To...
Nuclear medicine leverages different types of radiometals for disease diagnosis and treatment, but these applications usually require them to be stably chelated. Given the often-disparate chemical properties radionuclides, it is challenging find a single chelator that binds all effectively. Toward addressing this problem, we recently reported macrocyclic macrodipa with an unprecedented "dual-size-selectivity" pattern lanthanide (Ln3+) ions, characterized by its high affinity both large small...
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A new method has been developed for the isolation of 223,224,225Ra, in high yield and purity, from a proton irradiated 232Th matrix. Herein we report an all-aqueous process using multiple solid-supported adsorption steps including citrate chelation to remove >99.9% barium contaminants by activity final radium product. procedure involving use three columns succession was developed, separation 223,224,225Ra thorium matrix obtained with overall recovery 91 ± 3%, average radiochemical purity...
Abstract The use of α-emitting radionuclides in targeted alpha therapy (TAT) holds great potential for treatment human diseases, such as cancer, due to the short pathlength and high potency α particle, which can localize damage cells while minimizing effects healthy surrounding tissues. In this review several having emission properties applicable TAT are discussed from a radiochemical point view. Overviews production, separation chelation aspects relative developing radiopharmaceuticals...
Actinium-225 (225Ac, t1/2 = 9.9 d) is a promising candidate radionuclide for use in targeted alpha therapy (TAT), though the currently limited global supply has hindered development of suitable Ac-chelating ligand and 225Ac-radiopharmaceuticals towards clinic. We at TRIUMF have leveraged our Isotope Separation On-Line (ISOL) facility to produce 225Ac resulting radioactivity screen number potential 225Ac-radiopharmaceutical compounds.MBq quantities parent radium-225 (225Ra, 14.8 were produced...
Here, we present the synthesis and characterization of a new potentially nonadentate chelator H4pypa its bifunctional analogue tBu4pypa-C7-NHS conjugated to prostate-specific membrane antigen (PSMA)-targeting peptidomimetic (Glu-urea-Lys). is very functionally versatile biologically stable. Compared conventional chelators (e.g., DOTA, DTPA), has outstanding affinities for both 111In (EC, t1/2 ≈ 2.8 days) 177Lu (β-,γ, 6.64 days). Its radiolabeled complexes were achieved at >98% radiochemical...
The radionuclide 213Bi can be applied for targeted α therapy (TAT): a type of nuclear medicine that harnesses particles to eradicate cancer cells. To use this application, bifunctional chelator (BFC) is needed attach it biological targeting vector deliver selectively Here, we investigated six macrocyclic ligands as potential BFCs, fully characterizing the Bi3+ complexes by NMR spectroscopy, mass spectrometry, and elemental analysis. Solid-state structures three revealed distorted...
Terbium radioisotopes (149Tb, 152Tb, 155Tb, 161Tb) offer a unique class of radionuclides which encompass all four medicinally relevant nuclear decay modalities (α, β+, γ, β-/e-), and show high potential for the development element-matched theranostic radiopharmaceuticals. The goal this study was to design, synthesise, evaluate suitability crown-TATE as new peptide-conjugate radiolabelling [155Tb]Tb3+ [161Tb]Tb3+, assess imaging pharmacokinetic properties each radiotracer in tumour-bearing...
TRIUMF has a long history of medical isotope production. For more than 40 years, the Life Sciences Division at produced isotopes for Positron Emission Tomography (PET) local hospitals. Recently, division taken on challenge to expand facility's repertoire imaging treatment. At smallest cyclotron with energy 13 MeV, radiometals are being in liquid target which is typically used PET This effort makes available early stage research and preclinical trials. beam 24 we produce 99mTc from 100Mo...