A5087690273- Radiopharmaceutical Chemistry and Applications
- Medical Imaging Techniques and Applications
- Nuclear Physics and Applications
- Boron Compounds in Chemistry
- Medical Imaging and Pathology Studies
- Radiation Therapy and Dosimetry
- Particle accelerators and beam dynamics
- Radioactive Decay and Measurement Techniques
- Crystallization and Solubility Studies
- Advanced X-ray and CT Imaging
- Advanced Radiotherapy Techniques
- X-ray Diffraction in Crystallography
- Prostate Cancer Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Particle Accelerators and Free-Electron Lasers
- Radiation Dose and Imaging
- Radiation Effects and Dosimetry
- Spinal Fractures and Fixation Techniques
- Advanced Power Generation Technologies
- Medical Imaging and Analysis
- Lanthanide and Transition Metal Complexes
- Electron and X-Ray Spectroscopy Techniques
- Metal and Thin Film Mechanics
- Advanced Combustion Engine Technologies
TRIUMF
2017-2021
University of British Columbia
2017-2020
Bridge University
2020
University of Victoria
2011-2012
McMaster University
1970
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 Lead-212 ( 212 Pb, t 1/2 = 10.6 h) and lead-203 203 51.9 are an element-equivalent, or a matched theranostic radioisotope pair that show great potential for application in targeted radionuclide therapy (TRT) single-photon emission computed tomography (SPECT), respectively. At TRIUMF we have produced both Pb using TRIUMF’s TR13 (13 MeV) 500 MeV cyclotrons, subsequently purified evaluated radioisotopes series of pyridine-modified DOTA analogues comparison to the...
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...
Effective use of the decay chain in targeted internal radioimmunotherapy requires retention both and progeny isotopes at target site. Imaging-based pharmacokinetic tests these pharmaceuticals must therefore separately yet simultaneously image multiple that may not be colocalized despite being part same chain. This work presents feasibility studies demonstrating ability a microSPECT/CT scanner equipped with high energy collimator to two components chain: (218 keV) (440 keV). Image quality...
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...
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...
With recent impressive clinical results of targeted alpha therapy using 225Ac, significant effort has been directed towards providing a reliable and sufficient supply 225Ac to enable widespread 225Ac-radiopharmaceuticals. TRIUMF begun production via spallation thorium metal with 480 MeV protons. As part this program, new 225Ac-production target system capable withstanding the power deposited by proton beam was designed its performance simulated over range potential operating parameters....
The development of alpha-emitting radiopharmaceuticals using 211At requires quantitative determination the time-dependent nature biodistribution. However, imaging-based methods for acquiring this information with have not found wide-spread use because its low abundance decay emissions suitable external detection. In publication we demonstrate theranostic abilities 211At/209At isotope pair and present first-ever 209At SPECT images. VECTor microSPECT/PET/CT scanner was used to image a...
To design a postprocessing 3D adaptive median filter that minimizes streak artifacts and improves soft-tissue contrast in postoperative CT images of brachytherapy seed implantations.The works by identifying voxels are likely streaks estimating more reflective voxel intensity using intensities adjacent slices applying over not identified as seeds. Median values computed 5 x mm region interest (ROI) within the volume. An acrylic phantom simulating clinical implant arrangement containing...
To investigate the effects of brachytherapy seed size on quality x-ray computed tomography (CT), ultrasound (US), and magnetic resonance (MR) images localization through comparison 6711 9011 (125)I sources.For CT images, an acrylic phantom mimicking a clinical implantation plan embedded with low contrast regions interest (ROIs) was designed for both 0.774 mm diameter (standard) 0.508 (thin) models (Oncura, Inc., GE Healthcare, Arlington Heights, IL). Image metrics were assessed using...
The ISAC facility (Isotope Separation and Acceleration) at TRIUMF has recently started to provide isotopes for pre-clinical nuclear medicine studies. By irradiating ISOL OnLine) targets with a 480 MeV proton beam from the H- cyclotron, can deliver large variety of radioactive isotope beams (RIB) research in fields astrophysics, structure material science half-lives down few milliseconds via an electrostatic beamline network. For collection medical isotopes, typically range hours or days, we...
There is growing interest in finding new sources of 225Ac, an isotope with potential use the treatment metastatic disease. Proposed production alternatives include proton irradiation thorium above 100 MeV, however, concerns exist about co-production long-lived and toxic 227Ac. This work describes design simulated yields for a target that will be irradiated at TRIUMF, also proposes post-irradiation chemical isolation procedure produces two separate 225Ac products: first by direct from...
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...
The ISAC facility (Isotope Separation and ACceleration) at TRIUMF provides a wide range of radioactive isotope beams (RIB) for research in the fields nuclear astrophysics, structure material science by irradiating ISOL-type On-Line) targets with 480 MeV proton beam from H -cyclotron.We have developed compact collection device implantation mass-separated RIB on target disc energies between 20-55 keV.We also method to retrieve >95% activity chemical etching investigated alpha recoil separation...
Thorium targets were irradiated with 438-MeV protons, resulting in spallation and high-energy fission reactions. The measured production cross sections of 38 nuclides the mass range 83 to 233 are reported. These cross-section data useful for validating nuclear interaction models compared simulated calculated using three different Monte Carlo packages, fluka (version 2011.2x.7), geant4 10.6, Liege intranuclear cascade model abla version 3.1 evaporation code), binary model). also estimating...
Abstract Background: Lead-212 ( 212 Pb, t 1/2 = 10.6 h) and lead-203 203 51.9 are an element-equivalent, or a matched theranostic radioisotope pair that show great potential for application in targeted radionuclide therapy (TRT) single-photon emission computed tomography (SPECT), respectively. At TRIUMF we have produced both Pb using TRIUMF’s TR13 (13 MeV) 500 MeV cyclotrons, subsequently purified evaluated radioisotopes series of pyridine-modified DOTA analogues comparison to the...