Mr
Konstantin Kokov
(National Research Center "Kurchatov Institute", Moscow, Russia)
Targeted alpha therapy is actually one of the most promising and rapidly progressing method of treatment of oncological diseases. Of certain interest for radionuclide therapy is 212Pb beta emitter with its daughter nuclides (212Bi and 212Po) undergoing α-decay which allows one to regard 212Pb as an in vivo generator of alpha-particles.
In this connection, a new method of 212Pb radionuclide...
Mr
Robin Merkx
(Radboudumc, Nijmegen, The Netherlands)
**Authors:** Robin Merkx, Annemarie Kip, Egbert Oosterwijk, Michael Wheatcroft, Alfred Morgenstern, Frank Bruchertseifer, Peter Mulders, Mark Rijpkema, Sandra Heskamp
**Background:** Despite progress in the treatment of clear cell renal cell carcinoma (ccRCC), the prognosis of patients with metastasized disease remains poor. Therefore, novel treatment options need to be developed. A rapidly...
Dr
Reinier Hernandez
(University of Wisconsin-Madison)
Preclinical
Triple negative breast cancer (TNBC) remains the most lethal breast cancer histology. Currently, approved targeted therapies for TNBC do not exist, and novel tumor-targeted interventions to complement/supplant the current standard of care using chemotherapy are urgently needed [1]. Our research group has developed a series of tumor-avid alkyphosphocholine analogs (APC) that can carry a...
Prof.
Mike Sathekge
(University of Pretoria)
Purpose: 225Ac- Prostate-specific membrane antigen (PSMA)-617 is a highly promising novel compound for therapy of prostate cancer. A remarkable therapeutic efficacy has been demonstrated in heavily pre-treated metastatic castration-resistant prostate cancer (mCRPC) patients, with xerostomia as the main side effect. A promising strategy for minimization of side effects is based on optimization...
Prof.
Alfred Morgenstern
(European Commission, Joint Research Centre (JRC), Karlsruhe, Germany)
225Ac-PSMA617 is a novel and highly promising compound for treatment of prostate cancer. Since treatment of the first patient in early 2014, to date more than 330 prostate cancer patients have received a total of approximately 800 therapeutic applications through collaboration of the European Commission's Joint Research Center with hospitals in Heidelberg (Germany), Pretoria (South Africa),...
Dr
Michael Fassbender
(Los Alamos National Laboratory)
***Introduction***-Thorium-226 (t1/2=30.6m) is an isotope of interest for targeted alpha therapy (TAT). It decays via a four alpha decay chain to long-lived (t1/2=22.3 y) Pb-210 with a 111 keV gamma-line (3.29%) that can be used for SPECT imaging; thus providing theranostic capabilities. A generator concept is necessary to provide a consistent supply of Th-226 from its parent U-230 (20.23 d)...
Dr
Christoph Denk
(Vienna University of Technology)
**Purpose & Introduction**
The α-emitter 211At is a highly promising radionuclide for targeted alpha therapy (TAT). High linear energy transfer renders alpha particles highly radio-toxic to adjacent cells, making TAT a efficient treatment option for cancer.[1]
211At is the only alpha emitter used in therapy that allows for covalent labeling, thus preventing the use of chelating ligands....
Dr
Kotaro Nagatsu
(Nat. Inst. for Quantum and Radiological Science and Technology)
[Introduction] Ac-225 (T1/2 = 10 d) is regarded as a promising alpha emitter for the targeted alpha therapy (TAT). Considering biodistribution of conjugated antibodies, as well as logistics in worldwide supply, a physical half-life of 10 days would be tolerable for keeping certain radioactivity in each case. Actinium shows a good compatibility to DOTA that is favorable in radiochemistry to...
Ms
Stephanie Rathmann
(McMaster University)
Antibody recruiting small molecules (ARMs) are a unique class of immune-stimulatory agents that contain two key regions: the antibody-binding terminus (ABT), which recruits endogenous antibodies, and the target-binding terminus (TBT), which interacts with the site of interest.(1,2) When bound to a cell, the endogenous antibodies can promote antibody-dependent cellular cytotoxicity (ADCC)...
Andrew Robertson
(Life Sciences Division, TRIUMF; Dept. of Physics and Astronomy, University of British Columbia)
TRIUMF has begun production of Ac-225 (t1/2 = 9.9 d) by irradiation of thorium metal with 480 MeV protons and has developed new methods for separating Ac-225 from these targets.
At TRIUMF’s 500 MeV Isotope Production Facility, targets containing thorium metal (8 g, 60 mm diameter, 0.25 mm thickness) welded inside an Inconel capsule are irradiated by 480 MeV protons to an...
77.
Actinium Biokinetics and Dosimetry: What is the Impact of Ac-227 in Accelerator-Produced Ac-225?
Prof.
Rebecca Abergel
(University of California, Berkeley)
Among the growing list of alpha-emitting isotopes now available for pharmaceutical development, Ac-225 can act as an in vivo alpha-generator radionuclide and is of great interest for new targeted alpha-therapy applications. To seek further development of Ac-225 bioconjugate therapeutics, ongoing efforts aim at addressing current limitations, including lacking supply of the radioisotope,...
Dr
Kazuya Kabayama
(Department of Chemistry, Graduate School of Science, Osaka University)
In the fall of 2015, the Graduate School of Science, Osaka University’s Graduate School of Science, the Graduate School of Medicine, and the Center for Nuclear Physics cooperated to establish the project “Formation of an International Medical Center for Advanced Cancer Therapy by Medical Collaboration” as an estimate request project. Currently, one-third of cancer patients in Japan have...
Dr
Jean-François GESTIN
(CRCINA, Inserm, CNRS, Université d’Angers, Université de Nantes, Nantes, France)
Background and Objectives: Current protein astatination protocols most often rely on reactions that were developed several decades ago. Yet these methods are generally suboptimal. However, given the quite low availability of the alpha emitter 211At, there is a need for new methodologies to limit the loss of radioactive material in each step. This can be achieved by improving reactions...
Dr
Lior Arazi
(Nuclear Engineering Unit, Faculty of Engineering Sciences, Ben-Gurion University, Beer-Sheva Israel)
Diffusing Alpha-emitters Radiation Therapy (‘Alpha DaRT’) is a revolutionary new cancer-treatment modality, which enables – for the first time - the treatment of solid tumors by alpha particles. The basic idea is to insert into the tumor an array of implantable seeds, whose surface is embedded with a low activity of radium 224. Each seed continuously emits into the tumor, by recoil, a chain of...
Prof.
Stavroula Sofou
(Johns Hopkins University)
Metastatic and/or recurrent chemoresistant Triple Negative Breast Cancer (TNBC) is currently incurable. TNBC accounts for 12-17% of breast carcinomas with the lowest 5-year survival rates among all breast cancer patients due to high proliferation and reoccurrence outside the breast combined with lack of effective targeted therapeutic modalities. For such cases, key to the progression of the...
Dr
Joseph Jurcic
(Columbia University Medical center)
Early studies using the humanized anti-CD33 monoclonal antibody lintuzumab labeled with β-emitters showed significant activity against acute myeloid leukemia (AML) but produced prolonged myelosuppression necessitating hematopoietic cell transplantation (HCT). Targeted α-particle therapy may produce more efficient tumor killing while sparing normal cells. An initial phase I trial of bismuth-213...
Dr
SUMITAKA HASEGAWA
(Radiation and Cancer Biology Team, National Institutes for Quantum and Radiological Science and Technology)
Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. Almost 1/3 of GC patients have distant metastasis at the time of diagnosis and 4-14% are liver metastasis (LM). The therapeutic efficacy of current standard treatments for LMGC is still limited and the five years survival is less than 10%. HER2 became a target for GC because 20% of GC is HER2-positive (HER2+)...
Mr
Connor Frank
(University of Saskatchewan), Mrs
Mackenzie E. Malo
(University of Saskatchewan)
Miscellaneous
There is a need in creating efficient and light weight radioprotectors which would protect against both sparsely and densely ionizing radiation for use in radiation therapy, nuclear industry, protection of military personnel and in space exploration. The presence of melanin pigment imparts a selective advantage to fungi promoting survival and cellular fitness. Selective growth of melanized...
Dr
Ichiro Nishinaka
(Tokai Quantum Beam Science Center, National Institutes for Quantum and Radiological Science and Technology (Ibaraki, Japan))
**Objectives**: $^{211}$At, an astatine radionuclide, with half-life of 7.2 h is one of the prospective candidates for targeted alpha radiotherapy of cancers. Astatine shows some different chemical behaviors in comparison with its homologue iodine. The understanding of basic properties of astatine has been required to develop targeted alpha therapy agents for cancers [1]. In this work,...
Dr
Sture Lindegren
(Radiation Physics Gothenburg University Sweden)
Introduction
There are a consensus around the clinical potential of astatine-211 (211At), but only a limited number of research facilities work with the nuclide. There are three main reason for this which all are related to the chemistry infrastructure:
• Despite the fairly straight way of producing the rare alpha emitting element 211At, the production is scarce. There are a number...
Mr
Ali Alshehri
(Queen's University Belfast)
BACKGROUND
The majority (~90%) of patients with metastatic prostate cancer will have multiple bony metastases. Despite being the most common area of metastases in prostate cancer, reliably evaluating the burden of bony metastases at baseline and monitoring response to different therapeutic interventions is challenging and not standardised.
Isotope Bone Scan (IBS) is the most widely...
Dr
Diane Abou
(Washington University School of Medicine)
Alpha particle therapy is predicated on high energy emissions (MeV) with path lengths of only several cell diameters (μm). It has generated tremendous interests since the approval of the first in class alpha particle emitting radionuclide, Xofigo or 223Ra-dichloride. This agent is utilized for the treatment of castrate resistant prostate cancer, with successful outcomes with patient...
Mrs
Weronika Gawęda
(Institute of Nuclear Chemistry and Technology)
Among all alpha particle emitters, only a few nuclides are in considerable interest for targeted radionuclide therapy because of their properties, such as half-live, high cytotoxicity and short path length. One of the most important issues, which affects wider use of targeted α therapy in nuclear medicine, is the availability and the price of the radionuclides.
223Ra, as radium chloride, is...
Dr
Julian Rees
(Lawrence Berkeley National Lab)
The targeted delivery of alpha-generating radionuclides such as actinium-225
and thorium-227 is emerging as a promising treatment approach for a range of cancers. Advances in protein engineering are driving new developments in targeted drug delivery through increased availability of monoclonal antibodies and similar delivery vehicles. This work utilizes a modular, solid-phase synthetic method...
Dr
Naoyuki Ukon
(Fukushima Medical University)
Alpha particle emitting radionuclides are suitable for targeted radionuclide therapy (TRT), because of their short range in the tissue and high linear energy transfer. 211At is considered to be one of the ideal nuclides for TRT. A new generation of alpha particle compounds for TRT including meta-211At-astato-benzylguanidine (211At-MABG) are expected to have strong therapeutic efficacy with...
Dr
Leticia Arnedo-Sanchez
(Lawrence Berkeley National Laboratory)
Actinium-225 (225Ac) holds remarkable potential as radionuclide for targeted alpha-particle therapy (TAT) due to its advantageous properties, i.e. 10-day half-life and radioactive decay by emission of 4 alpha particles. To create a targeted alpha therapeutic comprising this radiometal, one must assemble two additional parts: a targeting moiety and a chelating ligand. Developing rationally...
Dr
Ashley Dame
(Oak Ridge National Labratory)
The chemical separation of actinium from proton-irradiated 232Th targets is being performed as part of a tri-laboratory (Oak Ridge National Laboratory, Brookhaven National Laboratory, and Los Alamos National Laboratory) effort focused on the accelerator production of 225Ac. Actinium-225 (t1/2 = 9.92 days) is produced by proton irradiation of a thorium metal target via the 232Th[p,x]225Ac...
Dr
Justin Griswold
(Oak Ridge National Laboratory)
Nuclide Production Supply
Comparison of Reactor Production of 229Th vs. Accelerator Production of 229Th at Oak Ridge National Laboratory
J. R. Griswold, R. Copping, D. W. Stracener, R. Howard, R. Boll, C. U. Jost, S. H. Bruffey, D. Denton, L. Heilbronn, and S. Mirzadeh
Actinium-225 (t1/2 = 10.0 ± 0.1 d) is one of the more effective radioisotopes used in alpha radioimmunotherapy. It has been used to treat...
Dr
Stosh Kozimor
(Los Alamos National Laboratory)
Targeting
Targeted alpha therapy (TAT) represents an emerging technology that has potential in treatment of disease. Amongst many isotopes showing promise in TAT, 225-actinium (225Ac) stands out. Its half-life is compatible with many medical applications and its decay is accompanied by emission of four alpha-particles, which augments 225-Ac’s therapeutic benefit in comparison to isotopes that produce...
Dr
Kris Barreto
(University of Saskatchewan)
Barreto K1, Causey P2, Solomon VR3, Bernhard W1, Sutherland A1, Wilson JJ4, Geyer CR1, Sadowski I5, Fonge H3,6.
1Department of Pathology and Laboratory Medicine, University of Saskatchewan
2Canadian Nuclear Lab, Chalk River, ON
3Department of Medical...
Bin He
(Radiopharmaceuticals Imaging and Dosimetry)
Pb-212 (T1/2 = 10.6h) has gained considerable interest in targeted alpha-therapy (TAT) since it serves as an in vivo generator for Bi-212 (T1/2 = 61 m), producing both α- and β-particles. Accurate dosimetry requires estimates of organ activity at multiple time points. Imaging Pb-212 is challenging because of the relatively low administered activities, complicated decay scheme in including...
Dr
Jerry Nolen
(Argonne National Laboratory)
Critically needed radionuclides for cancer therapy include the alpha-emitter 211At [1] and therapeutically useful Auger-electron emitters. The ATLAS (Argonne Tandem Linac Accelerator System) superconducting linac at Argonne National Laboratory is suitable for production of these radionuclides. Our work is initially focusing on demonstrating production capabilities for 211At (7.2 h half-life)...
Mr
abdelmjid Aiboud
(National Energy Center of Nuclear Science and Technology (CNESTEN)- Morocco)
OBJECTIVE:
The main aim of this study is to develop a new microbiological control method for the solution of iodine 131 in a closed system for radiopharmacy services not equipped with a class A Hot Cell dedicated to microbiological analysis according to GMP requirements.
METHODS:
The method is based on the preparation of perforated petri dishes containing three culture media. The...
Mr
Muath Helal
(College of Pharmacy and Nutrition, University of Saskatchewan)
In Canada, there were over half-a-million cases of serious fungal infections diagnosed in 2017. However, there is a low number of medications available for mycoses. Therefore, the need for a low toxicity, high efficient and low resistibility therapy is highly apparent. Radioimmunotherapy (RIT) utilizes antigen-antibody interaction to deliver lethal doses of ionizing radiation to cells. FDA,...
Prof.
George Sgouros
(Johns Hopkins Medical Institute)
Actinium-225 (225Ac) has a 10-day half-life and a decay scheme that yields four alpha-particle emissions. This radionuclide is produced by a generator system from the decay of thorium-229. Accelerator-produced 225Ac via thorium-232 irradiation (denoted 225/7Ac) contains a low percentage (0.1-0.3%) 227Ac; (21.77 year half-life) at end of bombardment. The biological consequences of this...
Mr
Inki Lee
(Korea Institute of Radiological and Medical Sciences)
Purpose: To predict the internal dosimetry of 225Ac-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-trastuzumab and 225Ac-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-trastuzumab in breast cancer using 64Cu-NOTA-trastuzumab, a novel PET tracer for the HER2 and 64Cu-DOTA-trastuzumab.
Methods:
Prior to injecting the radiotracer, 45 mg of cold trastuzumab was...
Dr
Sang-Keun Woo
(Korea Institute of Radiological and Medical Sciences)
Preclinical
Purpose:
Evaluation of internal dosimetry should have performed before injection of theranostic radiopharmaceuticals. The aim of this study was to estimate the 64Cu-PSMA-617 biodistribution in mice and human absorbed dose of 64Cu and 225Ac-PSMA-617.
Materials and Methods:
The radiolabeling efficiency of 64Cu-PSMA-617 was showed over 95%, and stabilities of 64Cu-PSMA-617 has remained over...
Dr
Jessie Nedrow
(Johns Hopkins University)
Preclinical
Background.
Very late antigen 4 (VLA-4; also called integrin α4β1) is overexpressed in melanoma tumors with an active role in tumor growth, angiogenesis, and metastasis. This makes VLA-4 an ideal antigenic target for targeted alpha therapy. The expression of VLA-4 on primary melanomas in human correlates with the development of metastasis and has been associated with high risk of metastasis...
Jonathan Fitzsimmons
(Medical Isotope Research & Production Program, Collider-Accelerator Department, Brookhaven National Laboratory)
Targeted alpha therapy with Actinium-225 (225Ac) or its daughter Bismuth-213 (213Bi) is an emerging and promising treatment for various types of cancers. 225Ac can be produced from a 229Th/225Ra generator system or from proton irradiated 232Th at high or 226Ra at low proton energies. Several types of inorganic ion exchange materials were synthesized to aid in chemical separations. Distribution...
Dr
Dohyun Kim
(Collider-Accelerator Department, Brookhaven National Laboratory, Upton, NY 11973, USA)
Alpha-emitting Ac-225 is a radionuclide being developed and used in the treatment of some cancers [1]. Currently, the Department of Energy (DOE) isotope program’s Tri-Lab Effort (Brookhaven National Laboratory, Oak Ridge National Laboratory, Los Alamos National Laboratory) effort provides Ac-225 from a Thorium target irradiated with a high energy proton beam [2]. We have a plan to make Ac-225...
Prof.
Barry Allen
(Western Sydney University)
The limitations of many systemic cancer therapies are that they are not potentially curable and recurrence is common. In particular, radio-immunotherapy with beta emitting radioisotopes is not curative and most vectors are cancer type specific. To overcome these limitations, new therapies are needed that are potentially curative, have minimal adverse events in humans and preferably have...
Mr
Ravendra Garg
(University of Saskatchewan)
The HIV epidemic is a major global health threat. Nowadays HIV-infected individuals live much longer due to the inhibition of the viral replication by combined anti-retroviral therapy (cART). However, cART fails to eradicate the residual HIV-infected cells, therefore, virus persists and continues to cause damage both systemically and to central nervous system (CNS). HIV enters the CNS in...
Dr
Wojciech Dawicki
(University of Saskatchewan)
Daratumumab is a human cytolytic antibody specific for CD38 that is used clinically for treatment of patients with multiple myeloma (MM). Current therapeutic regimens require multiple injections over months of treatment, therefor increasing the potency of daratumumab to shorten the length of treatment would be very advantageous. 225Ac is an -particle emitting radionuclide that has potent...
Mr
EMMANUEL NYARKO APPIAH
(TERNOPIL STATE MEDICAL UNIVERSITY)
In Oncology Regional Hospital Ternopil in 2015 -2017
Supervisors:
ABSTRACT: The process of treatment of patients with metastatic castrate-resistant prostate cancer (mCRPC) is pushing the boundaries of oncological treatments. The Ukrainian Society of Nuclear Medicine under the European Commission, Joint Research Centre has agreed on radium-223 chloride ((223) RaCl2) for the...
Dr
Natalie Grinshtein
(Fusion Pharmaceuticals)
Objectives:
Insulin-like growth factor-1 receptor (IGF-1R) is an oncogenic protein that is over-expressed in multiple solid tumors. IGF-1R targeted therapeutics have not demonstrated clinical efficacy for treating cancers either as stand-alone agents or in combination with other therapies. Despite this, targeted alpha therapeutic agents (TATs) may be ideal for treating IGF-1R expressing...
Dr
Sang-Keun Woo
(Korea Institute of Radiological and Medical Sciences)
Purpose:
Image-based absorbed dose calculation studies have been performed to evaluate the characteristics of theranostic radiopharmaceuticals. The aim of this study was to evaluate the 64Cu and 225Ac-DOTA-trastuzumab absorbed dose in mice using image-based Monte Carlo simulation.
Materials and Methods:
64Cu-DOTA-trastuzumab PET image was acquired at 3 time point at 3, 24, and 48 hour...
Prof.
George Sgouros
(Johns Hopkins Medical Institute)
225Ac-Lintuzumab- is an alpha-particle emitter labeled anti-CD33 antibody that is in clinical trial evaluation for the treatment of patients with leukemia and myelodysplastic syndrome (MDS). It is also being developed as a targeted conditioning regimen to irradiate and ablate the bone marrow as part of a marrow transplant treatment regimen. We examine the influence of target cell number on the...
Ms
Tong Liu
(Candadian Nuclear Laboratories)
Background:
Radiotherapy is one of the commonly used approaches to treat cancer. Current research trend and breakthroughs in radiotherapy are focusing on high linear energy transfer (LET) radiation such as alpha particles. Targeted Alpha Therapy (TAT) is the most important application of alpha particles in the development of radiotherapy in the past decade. This paper highlights the research...
Mr
Francisco Liberal
(Queen's University Belfast)
Preclinical
α-particle emitting radionuclides have been increasingly used in cancer treatment with particular interest for the treatment of micrometastases, due to the recently demonstrated survival benefit of Radium-223 (223Ra) in the treatment of bone metastases [1]. However, the reasons for its efficacy in comparison to previous beta emitters remains poorly understood. There is a pressing need to model...
Dr
Kazuhiro Ooe
(Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine)
Objectives: Astatine-211 (211At) is an alpha-emitting radionuclide suitable for targeted alpha therapy. Because At is a heavier homolog of iodine, astatide ion (At⁻) is expected to be applied to the treatment of thyroid cancer. In this study, 211At was treated by ascorbic acid (AA) as reducing agent to prepare At⁻. We aimed to evaluate the uptake change in the thyroid...
Dr
Albertsson Per
(Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden)
Eliminating microscopic residual disease with α-particle radiation is theoretically appealing. Following extensive preclinical work with α-particle emitting astatine-211 (211At), we performed a phase I trial in epithelial ovarian cancer (EOC). This was a first-in-class intraperitoneal (i.p.) α-particle therapy and the first in human study using the conjugate 211At-MX35, a murine monoclonal...
Dr
Isabelle Quelven
(CRIBL, CNRS UMR 7276, INSERM 1262, University of Limoges, France ; Nuclear Medicine Department, Limoges University Hospital, France)
Background: Non-Hodgkin’s Lymphoma (NHL) is the 8th most commonly diagnosed cancer in men and 11th in women. Immunotherapy with anti-CD20 monoclonal antibody rituximab in combination with chemotherapy is used as a first line treatment and significantly improves response rate and survival. However, many relapses are observed. Radioimmunotherapy (RIT) is then an emerging second line option for...
Mr
Kristof Dockx
(Institute for Nuclear and Radiation Physics, KU Leuven)
Over the last few years, several studies have proven the effect of targeted alpha therapy using 225Ac and 213Bi[1,2,3]. One of the crucial bottlenecks in upscaling current studies and moving to clinical trials is the availability of these isotopes. The current production methods cannot provide sufficient quantities of 225Ac or its daughter 213Bi. Furthermore, some of these production...
Dr
Atsushi Toyoshima
(Institute for Radiation Sciences, Osaka University)
Astatine (At)-211 is one of the most promising radionuclides for the targeted alpha therapy (TAT). In Osaka University, we have recently started the collaborative project for the TAT using 211At which can be produced in nuclear reactions using an accelerator. At present, cyclotron production, chemical separation, radiopharmaceuticals preparation, and pre-clinical trials of...
Mr
Miguel Toro-Gonzalez
(Virginia Commonwealth University)
Targeting
**Purpose:** To assess the in vitro retention of therapeutically relevant radionuclides such as in vivo α-generators Ra-223, Ac-225, and Th-227 in lanthanide phosphate (LnPO4) and lanthanide vanadate (LnVO4) core-shell nanoparticles (NPs) towards their promising application as multifunctional platforms in nanomedicine.
**Method and Materials:** LnPO4 and LnVO4 core-shell NPs doped with either...
Prof.
Kevin Prise
(Queen's University Belfast)
Despite the effectiveness of 223RaCl2 for treating castration resistant prostate patients with symptomatic bone metastatic disease, its mechanisms of action are still unclear. Even established dosimetric approaches differ considerably in their conclusions. With the rapid growth in the interest of alpha-targeted radionuclide approaches, in silico tumour models bring a new perspective to this as...
5.
Microdosimetric and Biokinetic Modelling of Alpha-Immuno-Conjugate Transport in Endothelial Cells
Dr
Tao Xu
(CNL)
Background and Objective:
The characterization of the Alpha-Immuno-Conjugate (AIC) targeted delivery process under vascular environment is very challenging due to the small scale of AIC particles, decay chain of the labeled radionuclide and the complex in vivo vascular system. To understand such a complex system, computational biokinetic model and microdosimetric model have been developed at...
Ms
LILY LI
(Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, Vancouver BC, V6T 1Z1, Canada; Life Sciences Division, TRIUMF, 4004 Wesbrook Mall, Vancouver BC, V6T 2A3, Canada)
Radiochemistry
The short particle range of alpha particles offers advantages for localized cancer treatment, sparing neighboring healthy tissue. Particularly interesting alpha-emitting radioisotopes include long-lived 225Ac (t1/2=9.92d) and 227Th (t1/2=18.7d), while the former also generates four net alpha particles through the short-lived progeny, rendering it highly potent. The key is to securely deliver...
Dr
James Harvey
(NorthStar Medical Technologies, LLC)
Ac-225 and its daughter Bi-213 have become increasingly important in clinical research for potential treatment of various diseases. The current US production of Ac-225 is limited to about 900 mCi annually from Oak Ridge National Laboratory. While there are limited sources of the stock material used to produce Ac-225, there are options available to meet this need. NorthStar has previously...
Dr
Amer A. Al Qaaod
(Postdoctoral fellowship)
Nuclide Production Supply
Abstract
The expected increase in radionuclide demand for treatment of various tumor diseases has led to the investigation of alternative production routes to provide sufficient amount of medical isotopes[1]. In Targeted Alpha Therapy (TAT), there is a present and future need for the Ac-225 and Bi-213, as the most promising alpha emitting isotopes, one of the limited ways to provide these...
Dr
Nadia Benabdallah
(Institute for Radiological Protection and Nuclear Safety)
Background: In nuclear medicine, beyond providing a starting administered activity for clinical studies, dosimetry has an important role in determining optimal treatment regimens and to identify patients in whom treatment is likely to have little benefit. For alpha-emitter radiopharmaceuticals, a personalized dosimetry is challenging because of the short range of alpha-particles. So, in order...
Adam Mansfield
(Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.)
Introduction: Radiolabeling poly-ADP ribose polymerase 1 (PARP-1) inhibitors potentially enables targeted delivery of alpha-emitting isotopes directly to cancer cells overexpressing PARP-1. However, there is concern for bone marrow toxicity due to its intrinsically high PARP-1 expression. Therefore, we examined bone marrow toxicity at therapeutically relevant doses of an astatine-211 labeled...
Dr
Sophie Poty
(Memorial Sloan Kettering Cancer Center)
**Objective:** When the integrity of the DNA is impaired, a series of DNA damage responses lead to the recruitment, upregulation or activation of specific protein within the nucleus. When present in sufficient copies, these proteins can represent attractive targets for molecular imaging. This presentation will present our recent efforts to image DNA damage repair proteins via PET imaging...
Dr
Anders Josefsson
(Johns Hopkins University, School of Medicine)
Since the approval of Xofigo® against metastatic castrated resistant prostate cancer there has been a growing interest in α-particle emitting radiopharmaceutical therapy. Actinium-225 (T1/2=10days) is one α-particle emitter of interest with a total emission of four α-particles in its decay chain (221Fr: T1/2=4.9min; 217At: T1/2=32.3ms; 213Bi: T1/2=45.6min; 213Po: T1/2=4.2μs). Using a chelator...
Dr
Emma Aneheim
(University of Gothenburg, Sweden)
Pretargeted radioimmunotherapy (PRIT) has the potential to increase activity uptake in tumors relative to normal tissue compared with conventional radioimmunotherapy. In pretargeting there is preferably a three step administration of agents with different properties. Firstly the pretargeting molecules (usually antibody conjugates) are administered allowing for maximum tumor targeting during...
Prof.
Jeffrey Norenberg
(Radiopharmaceutical Sciences Program, UNM HSC)
Objectives: Evaluate pharmacokinetics of 225Ac-DOTATOC with and without kidney protection (KP); to compare 225AcNO3 or “free” 225Ac derived from accelerator production versus stockpile extraction; to estimate predicted radiation absorbed dose (RAD) to humans receiving 225Ac-DOTATOC; and to evaluate histopathology 90 days post-administration.
Methods: 225AcNO3-accelerator, 225AcNO3-stockpile,...
Dr
Martin Vlk
(Czech Technical University in Prague, Faculty of Nuclear Science and Physical Engineering, Department of Nuclear Chemistry, 115 19 Prague 1, Czech Republic)
Targeted alpha-particle therapy (TAT) is very rapidly evolving field of radionuclide therapy. Nevertheless, there are some severe issues that need to be addressed to enable TAT to be a leading modality in radionuclide therapy. The nuclear recoil effect that causes the daughter nuclei release from the original radiopharmaceuticals is critical for alpha emitters [1-2]. Moreover, targeting and...
Mr
Pavel Butkaliuk
(JSC “SSC RIAR”)
Quality & Regulatory Assurance
Among all radium isotopes, at least two are used in nuclear medicine. Bayer-manufactured 223RaCl2 (trade name Xofigo) is applied for palliative care of bone metastasis. Microsources containing 224Ra are under clinical trials to treat malignant tumors of skin and mucous membrane using diffusing α-emitter radiation therapy (DaRT) that involves controlled migration of 220Rn.
These two radium...
Dr
Holger J. Jensen
(Copenhagen University Hospital)
Production of At-211 at the Copenhagen University Hospital, Denmark.
Holger J. Jensen, PET and Cyclotron Unit, Copenhagen University Hospital, DK-2100, Copenhagen, Denmark.
**Objective**
There is a great interest in At-211 for alpha radio immunotherapy. However the production of At-211 is difficult and it can only be produced in few accelerator facilities worldwide. In Copenhagen we...
Dr
Elena Lapshina
(Institute for Nuclear Research of Russian Academy of Sciences)
Targeted alpha-therapy of various oncology diseases is based on the coupling of alpha-emitting radionuclides to tumour-selective carrier molecules. 230U (T1/2=20.8 d) is accumulated via decay of 230Pa and has strong potential for alpha-therapy due to 5 emitting alpha - particles with total energy 33.5 MeV. It can be used directly or as a parent of 226Th in a generator system.
A...
Dr
Meiring Nortier Nortier
(Los Alamos National Laboratory)
The DOE National Isotope Program for radionuclide production operates two intermediate energy, high intensity accelerator-based production facilities: The 100 MeV Isotope Production Facility (IPF) at Los Alamos National Laboratory and the 200 MeV Brookhaven Linac Isotope Producer (BLIP). They are two of only eight intermediate energy production facilities worldwide and often operate with...
Ms
Marjolein Verhoeven
(University of Gothenburg), Dr
Tom Back
(University of Gothenburg)
Purpose. Optimization of patient dosing for intraperitoneal α-radioimmunotherapy of microtumours can be performed with the help of a biokinetic model. The goal of this study was to investigate whether simulations of mathematical models can be confirmed by in vitro models. We used the α- camera micro-imaging technology to quantify cell binding of 211At-radiolabelled monoclonal antibodies to...
Dr
Brian Miller
(University of Colorado School of Medicine)
Over the last several years new quantitative digital autoradiography imaging tools have been developed that are sensitive to both alpha- and beta-particle emitters. These include scintillation-, gaseous-, and semiconductor-based radiation-detection technologies that localize the emission location of charged particles on an event-by-event basis at resolutions up to 20 µm FWHM. These imaging...
Dr
Hiroyuki Suzuki
(Graduate School of Pharmaceutical Sciences, Chiba University)
**Objectives:** Astatine-211 (211At) is an α-emitting radionuclide appropriate for medical use. To expand the application of 211At-labeled compounds to radiotheranostics, we developed neopentyl derivatives as a novel scaffold for radioiodination and astatination. The stability, biodistribution, and metabolism of 125I-labeled neopentyl derivatives were...
Dr
Roy Copping
(Oak Ridge National Laboratory)
Radium 226 (t1/2 = 1600 years) can be irradiated in a reactor to produce a variety of important medical radioisotopes. These isotopes can be chemically separated and purified after irradiation, and the radium can be recycled for future use. Since radium is highly radioactive, there are unique challenges with using radium as a target material. Also, the chemical properties of radium are not yet...
Dr
Joe M. O'Sullivan
(Centre for Cancer Research & Cell Biology, Queen's University Belfast, Belfast, Northern Ireland)
Background
The Ra-223 Phase III study (ALSYMPCA) was conducted before abiraterone became available. The Ra-223 iEAP study included abiraterone-treated patients. Here we assessed SSEs, overall survival (OS) and bone health agent (BHA) use in Ra-223–treated patients who received abiraterone as a prior treatment.
Methods
This open-label, single-arm trial enrolled patients with...
Dr
Yasuhiro Ohshima
(National Institutes for Quantum and Radiological Science and Technology)
**Purpose:** Targeted α-particle therapy is a promising option for patients with malignant pheochromocytoma. Recent observations of *meta*-211At-astato-benzylguanidine (211At-MABG) in a pheochromocytoma mouse model showed a strong anti-tumor effect, but its molecular mechanism remains elusive (Y. Ohshima et al., 2018). Here, we showed the first comprehensive RNA-sequencing (RNA-seq) data of...
Dr
Benedikt Feuerecker
(Klinikum rechts der Isar, department of nuclear medicine, Technical University of Munich, Munich, Germany)
**Aim:** Despite the approval of several new agents metastatic castration resistant prostate cancer is still a major medical challenge. The beta-emitting Lu-177-PSMA radioligand therapy (RLT) is a new option but its antitumor effect can decrease over time. The aim of this retrospective analysis was to investigate safety and efficacy of the alpha emitting Ac-225-PSMA-617 RLT in mCRPC after...
Prof.
Leszek Krolicki
(Medical University, Warsaw)
Leszek Krolicki1, Frank Bruchertseifer2, Jolanta Kunikowska1, Henryk Koziara3, Bartosz Królicki3, Maciej Jakuciński4, Dariusz Pawlak 5, Christos Apostolidis2, Rafał Rola6, Adrian Merlo7, Alfred Morgenstern2
1 Department of Nuclear Medicine, Medical University of Warsaw, Warsaw, Poland
2 European Commission, Joint Research Centre, Directorate for Nuclear Safety and Security, Karlsruhe,...
Dr
Manoj Gupta
(Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India)
Introduction
Prostate cancer patients with distant metastasis have a poor prognosis and developed resistance to all standard drugs at various time intervals. A therapeutic option which can alleviate symptoms and prolong survival is in-search for these patients. [177Lu] prostate specific membrane antigen ([177Lu]PSMA) is a novel drug based on the theranostic concept. Here, we have presented...
Daniel McAlister
(Eichrom TEchnologies, LLC/PG Research Foundation, Inc.)
A complete scheme for the selective separation of actinium and radium isotopes from bulk 232Th target material will be presented. The process may be applicable to the production of 225Ac and 227Ac via proton spallation on thorium targets. Thorium metal is dissolved in sulfuric acid with small amounts of HF. Actinium and radium are retained on cation exchange resin from the sulfate medium,...
Dr
Gannon Parker
(Los Alamos National Laboratory)
Targeted α-particle therapy (TAT) has been shown in recent years to be a promising route for the treatment of various forms of cancer, and may serve as an alternative to more traditional cancer treatment options. TAT takes advantage of an α-emitting radionuclide’s ability to deliver cytotoxic doses of radiation to tumor cells while causing minimal damage to surrounding healthy tissue. This is...
Dr
Choong Mo Kang
(Korea Institute of Radiological & Medical Sciences)
Dosimetry & Instrumentation
Objectives: Chimeric monoclonal antibody rituximab, which selectively binds to CD20 surface antigen on B lymphocytes, has become a standard treatment for non-Hodgkin’s lymphoma. This study aims to synthesize 64Cu-DOTA-rituximab and evaluate its potential for targeted alpha therapy by in vitro, in vivo studies, and evaluation of the dosimetry of 225Ac-DOTA-rituximab.
Methods: DOTA-rituximab...
Mr
David Bauer
(Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research)
**Objectives**
The radionuclides radium-223 and radium-224 are two alpha-emitting radionuclides with suitable properties for the TAT. To this date, radium-223 in form of [223Ra]radium chloride (Xofigo) is the only EMA and FDA approved alpha-emitting radiopharmaceutical. Due to its calcimimetic behavior, the radium ion is a bone-seeking therapeutic. To extend the radiopharmaceutical...
Dr
Raja Solomon Viswas
(University of Saskatchewan)
Introduction: Targeted alpha-particle therapy is a promising approach for breast cancer treatment. Anti-EGFR antibodies e.g. cetuximab, panitumumab, and nimotuzumab are used to treat different EGFR positive cancers. Especially, nimotuzumab is better tolerated and has low skin toxicities, because it’s “affinity optimized” binding characteristic ensures low transient binding to low...
Dr
Sabine Zitzmann-Kolbe
(Bayer AG, Pharmaceuticals Division)
Targeted alpha therapy (TAT) agents deliver high linear energy transfer (LET) alpha-radiation selectively to tumors. The first TAT approved is radium-223 which prolongs overall survival in metastatic castration resistant prostate cancer (mCRPC) patients with symptomatic bone metastasis. The PSMA targeted thorium-227 conjugate PSMA-TTC represents another TAT approach in mCRPC. It consists of a...
Dr
Ebrahim S. Delpassand
(RadioMedix Inc; Excel Diagnostics and Nuclear Oncology Center)
**Objectives:**
The high potency of alpha-emitters combined with high affinity of the somatostatin analogs provides the fundamental strength and rationale for using Targeted Alpha-emitter Therapy (TAT) in neuroendocrine cancers (NETs). The 212Pb-octreotate analog, (AlphaMedix™) will be the next generation of peptide receptor radionuclide therapy for the metastatic NETs patients. RadioMedix...
Ms
Sharayu Karkare
(University of Saskatchewan)
Introduction: Osteosarcoma is the most common non-hematologic primary bone malignancy. It has been reported that it is the most common primary malignant bone tumour and the fifth most common primary malignancy among adolescents and young adults. There is a need for alternative novel treatment approaches to osteosarcoma treatment, as conventional chemotherapy strategies are not effective in...
Mr
Michael Siegl
(Department of Otolaryngology Head and Neck Surgery, Technical University of Munich, Munich, Germany)
Preclinical
Introduction
------------
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Despite considerable improvements in surgery, radio- and chemotherapy over the last decades, the five-year overall survival has not changed significantly. Radio resistance is a frequent issue that impedes success in therapy. Tumor hypoxia often is causing this resistance, hence...
56.
The role of IAEA in the development of radiopharmaceutical sciences with focus on alpha emitters
Mr
Amirreza Jalilian
(IAEA)
The Radioisotope Products and Radiation Technology (RPRT) Section of IAEA has been implementing several activities focusing on the production and quality control of alpha emitter radioisotopes and radiopharmaceuticals as well as capacity building in the field, through Technical Meetings, Workshops, Publications and Conference Supports and the IAEA-Technical Cooperation projects.
As interest...
Dr
Marek Pruszynski
(Institute of Nuclear Chemistry and Technology)
**Objectives:** Nanobodies (Nbs) are the smallest antibody-derived fragments with beneficial pharmacokinetic properties for molecular imaging and radionuclide therapy. Human Epidermal Growth Factor Receptor type 2 (HER2) is overexpressed in numerous carcinomas and portends a poor prognosis. Therefore, HER2-targeting nanobodies are very attractive vectors for TRT, especially when labeled with...
Mr
Edouard nzambimana
(Burundi Bureau of Standards)
Ir Nzambimana Edouard, Msc, radiochemist, Burundi Bureau of Standards and Quality Control, Radiochemistry laboratory,alinzamed@yahoo.fr, nzambimana.1978@gmail.com
Abstract
Thorium with symbol Th is radioactive metal which emits the alpha rays. This metal can be founded in different forms and can cause the negatives impacts on human health and environment. This is the reason which...
Catherine Meyer
(Physics & Biology in Medicine Interdepartmental Graduate Program, David Geffen School of Medicine, UCLA.)
Background and Objective. Targeted alpha therapy shows promise as a treatment in metastatic castration-resistant prostate cancer (mCRPC), owing to the high dose deposition and short range characteristics of alpha particle radiation. Ac-225 decays via multiple alpha particles – each capable of inducing irreparable DNA double-strand breaks in cell nuclei. PSMA-617 is a targeting ligand with...
Dr
Robin de Kruijff
(Delft University of Technology)
Cancer, still presenting one of the major challenges in modern healthcare, leads to more than 8.8 million deaths annually. While the main treatment options include surgery, chemotherapy, and radiotherapy, increasing attention is given to brachytherapy in e.g. the treatment of prostate cancer. Advantages of brachytherapy, as compared to radical prostatectomy and external beam radiation therapy,...
Dr
Rose Boll
(ORNL), Ms
Shelley Van Cleve
(Oak Ridge National Laboratory)
Thorium-229 Generator Production of Actinium-225 at Oak Ridge National Laboratory
Shelley Van Cleve, Paul Benny, Thomas Dyke, Jay Kehn, Kayla Phillips, Rose Boll
Oak Ridge National Laboratory, Oak Ridge, TN 37831
Background and Objective: Oak Ridge National Laboratory (ORNL) is a major producer of 225Ac and supplies research and clinical trials for the treatment of various forms of cancer...
Dr
Ján Kozempel
(CTU in Prague)
Preclinical
Although 223RaCl2 has been approved for the treatment of bone metastases originating from mCRPC (EMA, FDA and others), further data on 223Ra biodistribution and possible metabolism tuning are needed particularly after the discovery of increased risk of death and fractures due to the interactions of 223Ra with abiraterone, prednisone/prednisolone...
Kevin John
(Los Alamos National Laboratory)
Nuclide Production Supply
The current availability of accelerator produced 225Ac from the US Department of Energy Isotope Program’s Tri-Lab (ORNL, BNL, LANL) Research and Production Effort to Provide Accelerator-Produced 225Ac for Radiotherapy will be presented. Additional details will be presented on recent production improvements and ongoing plans for further scaling up our operations. In addition, impacts...
Dr
Joe M. O'Sullivan
(Center for Cancer Research and Cell Biology, Queen’s University Belfast, Northern Ireland Cancer Center, Belfast City Hospital, Belfast, Northern Ireland)
Background
When the radium-223 Phase III clinical trial (ALSYMPCA) was conducted, abiraterone was an investigational agent that was only available through clinical trials. REASSURE is a prospective, observational clinical study of radium-223 in patients with mCRPC with a 7-year follow-up (NCT02141438). Patients could have had anti-hormonal agents, such as abiraterone, prior to receiving...
Dr
Aleksandr Vasiliev
(Institute for Nuclear Research Russian Academy of Sciences)
Among alpha emitters suitable for targeted alpha-therapy, 225Ac (T1/2 = 9.9 days) and the product of its decay 213Bi (46 min.) are the most promising. Clinical trials are confirming higher efficacy and less toxicity of the radiopharmaceuticals labeled with these radionuclides in comparison with similar beta-emitting ones. A prospective method of producing 225Ac (more than 1 Ci for a 10-day...
