Special Issue "Radioisotope Production and Applications"

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A special issue of Applied Sciences (ISSN 2076-3417).

Deadline for manuscript submissions: closed (31 July 2013)

Special Issue Editor

Guest Editor
Dr. Paul Schaffer (Website)

Head, Nuclear Medicine, TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, Canada V6T 2A3
Fax: +1 604 222 1074
Interests: radiochemistry; radiopharmaceutical development; molecular imaging; positron emission tomography, radioisotope production and applications

Special Issue Information

Dear Colleagues,

Molecular imaging has enabled health professionals and basic researchers to probe the function of living systems at the molecular level, enabling non-invasive studies into functional changes that take place during the onset and progression of disease, well before anatomical changes occur. Understanding the molecular progression of disease is changing the way it is diagnosed, staged and treated and will ultimately enable a paradigm of personalized healthcare.

Between 20 and 40 million single photon- and positron emission tomography (SPECT and PET) scans are performed each year around the world in patients suffering from heart ailments, cancer and neurological diseases like Parkinson’s and Alzheimer’s. With new biological questions about these diseases (and others) continuously emerging, novel ways of producing medical isotopes, converting them into radiopharmaceuticals and demonstrating in vivo efficacy are of paramount importance. Such an effort requires amalgamation of basic and applied research across the disciplines of physics, chemistry and biology—all of which are geared toward the development of better imaging protocols or contrast-enhancing biological probes.

The widespread acceptance of new and promising radioisotopes and radiopharmaceuticals is typically challenged by their availability and accessibility. Despite the advances in availability of medical cyclotrons in the hospital setting, new isotope production, isolation and application remains a difficult task for most institutions. Couple this with the anticipated shutdown of the world’s major 99mTc production reactor and accelerator-based production facilities will face an increasing responsibility to meet isotope demands of the healthcare community.

The need to install novel infrastructure and/or purchase isotope generators necessitates a substantial technical and financial commitment that may be difficult to justify, especially if preliminary biological studies are warranted to establish proof of feasibility for the isotopes in question. These obstacles likely inhibit the development of novel tracers that may possess a better match between the physical half-life of a promising new radioisotope and the pharmacokinetic profile of the vector to which it is attached.

This special issue of Applied Sciences, titled “Radioisotope Production and Application” aims to cover recent advances in the development of new and promising production methods for metallic and non-metallic medical isotopes, as well as new radiochemical techniques for radiopharmaceutical production and their use in novel applications. Reviews are also welcome.

Dr. Paul Schaffer
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Applied Sciences is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. For the first couple of issues the Article Processing Charge (APC) will be waived for well-prepared manuscripts. Article Processing Charge (APC) will be waived for well-prepared manuscripts submitted before the end of 2012, Article Processing Charge will be 300 CHF from 2013. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

Keywords

  • cyclotron
  • cyclotron target design, operation
  • isotope production, isolation
  • medical radioisotopes
  • radiometals
  • radiopharmaceutical chemistry
  • radiopharmaceuticals
  • positron emission tomography (PET)
  • single photon emission computed tomography (SPECT)
  • molecular imaging

Published Papers (5 papers)

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Research

Open AccessArticle CERN-MEDICIS (Medical Isotopes Collected from ISOLDE): A New Facility
Appl. Sci. 2014, 4(2), 265-281; doi:10.3390/app4020265
Received: 10 November 2013 / Revised: 27 January 2014 / Accepted: 25 February 2014 / Published: 16 May 2014
Cited by 5 | PDF Full-text (4706 KB) | HTML Full-text | XML Full-text
Abstract
About 50% of the 1.4 GeV CERN (European Organization for Nuclear Research, www.cern.ch) protons are sent onto targets to produce radioactive beams by online mass separation at the Isotope Separator Online Device (ISOLDE) facility, for a wide range of studies in fundamental [...] Read more.
About 50% of the 1.4 GeV CERN (European Organization for Nuclear Research, www.cern.ch) protons are sent onto targets to produce radioactive beams by online mass separation at the Isotope Separator Online Device (ISOLDE) facility, for a wide range of studies in fundamental and applied physics. CERN-MEDICIS is a spin-off dedicated to R&D in life sciences and medical applications. It is located in an extension of the Class A building presently under construction. It will comprise laboratories to receive the irradiated targets from a new station located at the dump position behind the ISOLDE production targets. An increasing range of innovative isotopes will thus progressively become accessible from the start-up of the facility in 2015 onward; for fundamental studies in cancer research, for new imaging and therapy protocols in cell and animal models and for pre-clinical trials, possibly extended to specific early phase clinical studies up to Phase I trials. Five hundred megabecquerel isotope batches purified by electromagnetic mass separation combined with chemical methods will be collected on a weekly basis. A possible future upgrade with gigabecquerel pharmaceutical-grade i.e., current good manufacturing practices (cGMP) batch production capabilities is finally presented. Full article
(This article belongs to the Special Issue Radioisotope Production and Applications)
Open AccessArticle Radiosynthesis and in Vivo Evaluation of Two PET Radioligands for Imaging α-Synuclein
Appl. Sci. 2014, 4(1), 66-78; doi:10.3390/app4010066
Received: 30 April 2013 / Revised: 7 February 2014 / Accepted: 27 February 2014 / Published: 17 March 2014
Cited by 2 | PDF Full-text (535 KB) | HTML Full-text | XML Full-text
Abstract
Two α-synuclein ligands, 3-methoxy-7-nitro-10H-phenothiazine (2a, Ki = 32.1 ± 1.3 nM) and 3-(2-fluoroethoxy)-7-nitro-10H-phenothiazine (2b, Ki = 49.0 ± 4.9 nM), were radiolabeled as potential PET imaging agents by respectively introducing 11C [...] Read more.
Two α-synuclein ligands, 3-methoxy-7-nitro-10H-phenothiazine (2a, Ki = 32.1 ± 1.3 nM) and 3-(2-fluoroethoxy)-7-nitro-10H-phenothiazine (2b, Ki = 49.0 ± 4.9 nM), were radiolabeled as potential PET imaging agents by respectively introducing 11C and 18F. The syntheses of [11C]2a and [18F]2b were accomplished in a good yield with high specific activity. Ex vivo biodistribution studies in rats revealed that both [11C]2a and [18F]2b crossed the blood-brain barrier (BBB) and demonstrated good brain uptake 5 min post-injection. MicroPET imaging of [11C]2a in a non-human primate (NHP) confirmed that the tracer was able to cross the BBB with rapid washout kinetics from brain regions of a healthy macaque. The initial studies suggested that further structural optimization of [11C]2a and [18F]2b is necessary in order to identify a highly specific positron emission tomography (PET) radioligand for in vivo imaging of α-synuclein aggregation in the central nervous system (CNS). Full article
(This article belongs to the Special Issue Radioisotope Production and Applications)
Figures

Open AccessArticle Dry Distillation of Radioiodine from TeO2 Targets
Appl. Sci. 2013, 3(4), 675-683; doi:10.3390/app3040675
Received: 26 July 2013 / Revised: 8 October 2013 / Accepted: 21 October 2013 / Published: 28 October 2013
PDF Full-text (1145 KB) | HTML Full-text | XML Full-text
Abstract
As medical cyclotrons are becoming more abundant, 123I and 124I are getting more attention as alternatives to 131I for diagnostics of thyroid disease. Both 123I and 124I provide better diagnostics, deliver less dose to patients and both [...] Read more.
As medical cyclotrons are becoming more abundant, 123I and 124I are getting more attention as alternatives to 131I for diagnostics of thyroid disease. Both 123I and 124I provide better diagnostics, deliver less dose to patients and both reduce the risk of thyroid stunning, facilitating subsequent therapy. Dry distillation of radioiodine from tellurium dioxide targets has become the standard approach to producing these radioiodines. Setting up such a production of radioiodine is associated with a lengthy optimization of the process and for this purpose natural tellurium is often used for economical reasons. In this paper, the distillation parameters are scrutinized to ensure optimal distillation temperature, in order to minimize time spent and prevent loss of expensive target material. It is further demonstrated how the individual iodine isotopes, produced from proton bombardment of natTe, will diffuse out of the target in a time dependent ratio. We believe the effect is due to the isotopes having their maximum cross section at different energies. The individual isotopes produced will thus have their highest concentration at different depths in the target. This results in individual mean diffusion lengths and diffusion times for the different isotopes. Full article
(This article belongs to the Special Issue Radioisotope Production and Applications)
Open AccessArticle Evaluation of a Wet Chemistry Method for Isolation of Cyclotron Produced [211At]Astatine
Appl. Sci. 2013, 3(3), 636-655; doi:10.3390/app3030636
Received: 24 July 2013 / Revised: 29 August 2013 / Accepted: 9 September 2013 / Published: 18 September 2013
Cited by 3 | PDF Full-text (691 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A “wet chemistry” approach for isolation of 211At from an irradiated bismuth target is described. The approach involves five steps: (1) dissolution of bismuth target in conc. HNO3; (2) removal of the HNO3 by distillation; (3) dissolution of [...] Read more.
A “wet chemistry” approach for isolation of 211At from an irradiated bismuth target is described. The approach involves five steps: (1) dissolution of bismuth target in conc. HNO3; (2) removal of the HNO3 by distillation; (3) dissolution of residue in 8 M HCl; (4) extraction of 211At from 8 M HCl into DIPE; and (5) extraction of 211At from DIPE into NaOH. Results from 55 “optimized” 211At isolation runs gave recovery yields of approximately 78% after decay and attenuation corrections. An attenuation-corrected average of 26 ± 3 mCi in the target provided isolated (actual) yields of 16 ± 3 mCi of 211At. A sixth step, used for purification of 211At from trace metals, was evaluated in seven runs. In those runs, isolated 211At was distilled under reductive conditions to provide an average 71 ± 8% recovery. RadioHPLC analyses of the isolated 211At solutions, both initial and after distillation, were obtained to examine the 211At species present. The primary species of 211At present was astatide, but astatate and unidentified species were also observed. Studies to determine the effect of bismuth attenuation on 211At were conducted to estimate an attenuation factor (~1.33) for adjustment of 211At readings in the bismuth target. Full article
(This article belongs to the Special Issue Radioisotope Production and Applications)
Figures

Open AccessArticle Routine Production of 89Zr Using an Automated Module
Appl. Sci. 2013, 3(3), 593-613; doi:10.3390/app3030593
Received: 9 May 2013 / Revised: 12 June 2013 / Accepted: 24 June 2013 / Published: 12 July 2013
Cited by 7 | PDF Full-text (1387 KB) | HTML Full-text | XML Full-text
Abstract
89Zr has emerged as a useful radioisotope for targeted molecular imaging via positron emission tomography (PET) in both animal models and humans. This isotope is particularly attractive for cancer research because its half-life (t1/2 = 3.27 days) is well-suited [...] Read more.
89Zr has emerged as a useful radioisotope for targeted molecular imaging via positron emission tomography (PET) in both animal models and humans. This isotope is particularly attractive for cancer research because its half-life (t1/2 = 3.27 days) is well-suited for in vivo targeting of macromolecules and nanoparticles to cell surface antigens expressed by cancer cells. Furthermore, 89Zr emits a low-energy positron (Eβ+,mean = 0.40 MeV), which is favorable for high spatial resolution in PET, with an adequate branching ratio for positron emission (BR = 23%). The demand for 89Zr for research purposes is increasing; however, 89Zr also emits significant gamma radiation (Γ15 keV = 6.6 R×cm2/mCi×h), which makes producing large amounts of this isotope by hand unrealistic from a radiation safety standpoint. Fortunately, a straightforward method exists for production of 89Zr by bombarding a natural Y target in a biomedical cyclotron and then separation of 89Zr from the target material by column chromatography. The chemical separation in this method lends itself to remote processing using an automated module placed inside a hot cell. In this work, we have designed, built and commissioned a module that has performed the chemical separation of 89Zr safely and routinely, at activities in excess of 50 mCi, with radionuclidic purity > 99.9% and satisfactory effective specific activity (ESA). Full article
(This article belongs to the Special Issue Radioisotope Production and Applications)

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