WORLD COUNCIL ON ISOTOPES - Production of Accelerator-Based Medical Radionuclides

01.Lead Article

Production of Accelerator-Based Medical Radionuclides

Syed M. Qaim Professor, Forschungszentrum Jülich (FZJ), Germany

2021 April

Editor-in-Chief, Radiochimica Acta

Vol.10 – Issue 4

01 Lead Article

Chair, Education and Training Committee of WCI

1

02 Isotope-related News

12

03 Sketches from the Secretariat

21

04 Future Conferences and Events

25

Jong Kyung Kim President Nigel Stevenson Immediate Past President Paul Dickman President-Elect Bernard Ponsard Chair, Industrial Applications Keon Wook Kang Chair, Medical Applications Timothy Payne Chair, Environmental Applications Carlo R. ChemalyChair, Info.Exchange& Cooperation Syed M. Qaim Chair, Education and Training Meera Venkatesh Chair, Publication Paul Dickman Chair, ICI Coordination Ira N. Goldman Chair, Long-Term Funding Woo-Geun Song Secretary-General

1. Introduction Radioactivity medicine,

applications

both

in

can

diagnosis

be and

found

in

internal

radiotherapy; the choice of a radionuclide for a particular application being governed by its decay properties. Diagnostic investigations are carried out using short-lived radionuclides which decay by isomeric transition (IT) or electron capture (EC) and thereby emit a single or a major γ-ray of energy between 70 and 250 keV, or by the emission of a positron. The former are used in single photon emission tomography (SPECT) and

WCI Secretariat 18F Seoul Forest IT Valley 77 Seongsuil-ro, Seongdong-gu, Seoul, Korea TEL: +82-2-3490-7141 Email: Secretary@wci-ici.org www.wci-ici.org

WORLD COUNCIL ON ISOTOPES

the latter in positron emission tomography (PET).

In internal radionuclide therapy, on the other hand, radionuclides emitting low-range highly1

ionizing radiation, i.e. α- or β- particles or conversion/Auger electrons, are used.

Radionuclides are produced using nuclear reactors as well as accelerators/cyclotrons and there are some common methodologies. Yet, there are some special features distinctly specific to the production at a cyclotron, resulting from the rapid loss of energy of the charged particle in matter, with consequent deposition of heat in the target. Thus, in accelerator production of radionuclides, particular attention needs to be paid to nuclear data and targetry.

2. Some Basic Aspects of Radionuclide Production using Accelerators Types of accelerators Over the last three decades several types of cyclotrons and accelerators have been developed to meet the specific demands of radionuclide production. The smallest machine is generally a proton accelerating cyclotron with energy of 11 or 12 MeV. It can be used to produce major short-lived β+ emitters

11C

and 18F (as described below). Next

in terms of size comes accelerators comprising of two particle machines with E p ≤ 20 MeV and Ed ≤ 10 MeV. These are ideally suited for the production of the commonly used PET radionuclides. Even higher energy machines have capabilities of producing many more radionuclides, in particular when, besides p and d, 3He and α-particle beams are also available. On the other hand, when energies above 100 MeV are under consideration, generally only a proton accelerator is applicable.

Nuclear data The role of nuclear data in the production of radionuclides was described in a previous Newsletter of WCI (cf. S.M. Qaim, May 2019). The data are mainly used to optimize a production route, i.e. to maximize the yield of the desired product and to minimize the yields of the radioactive impurities. In the present contribution, therefore, only one special feature, namely the production yield, is discussed in some detail.

In charged-particle production of radionuclides, the yield A (in Bq) over a certain energy range (E1 to E2), the so called “thick target yield”, is calculated by the modified activation equation given below.

WORLD COUNCIL ON ISOTOPES

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𝐸2

𝑁𝐿 ∙ 𝐻 𝑑𝐸 −1 −𝜆𝑡 𝐴= 𝐼 (1 − 𝑒 ) ∫ ( ) 𝜎(𝐸)𝑑𝐸 𝑀 𝑑(𝜌𝑥) 𝐸1

where NL is the Avogadro number, H the enrichment (or isotopic abundance) of the target nuclide, M the mass number of the target element, I the projectile current 𝑑𝐸

(particles s-1), λ the decay constant and t is the time of irradiation. The term (𝑑(𝜌𝑥)) describes the stopping power, σ(E)dE the cross section at energy E, and E1 and E2 are the lower and upper energy limits of the projectile in the target. Yields are generally calculated for a certain energy range for a current of 1 µA and an irradiation time of 1 h (MBq µAh-1). In some cases, saturation yields appear to be more meaningful (MBq µA-1). The calculated yield from the excitation function represents the maximum yield which can be expected from a given nuclear process under optimum conditions. In practice, however, the experimentally obtained yield in a high-current production run is invariably lower than the calculated yield, possibly due to beam positioning, radiation damage effects, loss in chemical processing, etc. Nonetheless, the calculated yield serves as an ideal value for optimizing a production target.

For the production of radionuclides, in general the four light mass charged particles, namely protons, deuterons, 3He- and α-particles are utilized, although 3He- and αparticles are used only when the other two particles either cannot produce the desired radionuclide or when purity problems exist. Because of its higher range in target and more common availability, the proton beam is more frequently used.

The standardized nuclear data for the production of many medical radionuclides are available at the IAEA website: https://www-nds.iaea.org/relnsd/vcharthtml/MEDVChart.html High-current targetry Regarding the large scale production of radionuclides in accelerators, high beam currents have to be used. The power density effective at the target is then rather high (up to a few kW/cm2). An efficient heat transfer is thus one of the prime requirements in target construction. Some typical target systems used at low and medium-sized WORLD COUNCIL ON ISOTOPES

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cyclotrons are described below. The constraint of low projectile energy and its rapid loss in the expensive enriched target material puts heavy demands on the development of an irradiation system.

A

B

C

Fig. 1. Typical solid target holders for irradiations:

Fig.2. Typical medium-pressure water target

(A) perpendicular beam, (B) slanting beam and (C)

system at a cyclotron.

He-cooled front window.

Solids. The sample (metal sheet, electroplated layer, a thin piece of alloy or a pellet) is irradiated in a vacuum, with the beam impinging on it either perpendicularly or at a slanting angle. The target holder is cooled by a water stream at the back. In another system, the target holder, again cooled by a water stream at the back, is separated from the cyclotron vacuum by a double foil window, which is cooled by He gas flow at a low pressure. The three configurations are shown in Fig. 1. The standard technology today either makes use of the slanting beam or the He-cooled double window in front.

The latter is used mainly in the production of radionuclides at low energy cyclotrons.

The slanting beam, on the other hand, is extensively utilized in commercial scale production of radionuclides, e.g.

67Ga

and

111In.

Under optimized conditions, a thin

electroplated layer of the target material is commonly irradiated with 30 MeV protons of beam currents of up to 800 µA. WORLD COUNCIL ON ISOTOPES

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Liquids. For the irradiation of liquids, small-sized pressurized targets have been developed to avoid radiolysis. A typical medium-pressure (up to 7 bar) target is shown in Fig. 2. It consists of a titanium target body, welded to two titanium foils which act as the front and back windows. The volume between the two foils is filled with the target material (1.3 ml of water). During irradiation, the target body and the back window are cooled with a stream of water and the front window with a stream of He. At the end of the irradiation, the target is emptied by releasing the pressure and purging it with He gas. In recent years, irradiation of some solutions have also been carried out in modified liquid targets.

Fig. 3. Target system for irradiation of an enriched rare gas and removal of the product radionuclide.

Gases. For irradiation of gases, advanced technology has been developed, especially for use at low-energy cyclotrons to produce short-lived positron emitters. From the practical point of view, the gas targets can be divided into two systems depending on the possibility of removal of the radioactive product, either directly with the target gas or in a second step after its deposition on the inner wall. The latter requires more effort.

A system developed at the Forschungszentrum Jülich for irradiation of highly enriched 82Kr

gas and isolation of the product radionuclide

WORLD COUNCIL ON ISOTOPES

82mRb

is shown in Fig. 3. The product 5

is efficiently removed from the target’s inner wall by introducing steam and is collected in water which is then trapped in a small container for further processing. The system has been used for the irradiation of other rare gases also, e.g. Ne, Ar, Kr and Xe to produce small amounts of

22Na, 38K, 75Br, 81Rb

and

123I,

respectively. A more advanced

technology has been developed at Karlsruhe and Vancouver to produce large quantities of

123I

by irradiation of the highly enriched

124Xe

gas. This technology is now

commercially available.

Other irradiation systems. In contrast to low and medium-sized cyclotrons, at accelerators delivering beams with energies above about 60 MeV, only solid targets are used and the construction of an irradiation device becomes somewhat easier, because a thick-walled target container with efficient cooling can be built in. In this configuration even a molten target material within a suitable container can be handled. This is done in practice, for example, in the production of the longer lived radionuclides 82Sr.

68Ge

and

Occasionally, a series of targets (tandem mode) is irradiated. It is then possible to

produce two radionuclides simultaneously.

Chemical processing There are two major aims of chemical processing of the irradiated target material: (a) to isolate the desired radionuclide in a pure form; (b) to recover the isotopically enriched target material for reuse.

Highly enriched target material is very commonly used in accelerator production of radionuclides. The latter aim is thus of great economic interest. The first aim, on the other hand, is of absolute importance with regard to medical application. The radiochemical separation has to be fast while handling short-lived products, and it should be adaptable to remote control and/or automation in order to reduce the radiation dose to the personnel. In general, both online and offline methods of separation of radionuclides have been used. The online method is mostly applied when the radionuclide produced is in gaseous form. For example, it is extensively used in the production of the short-lived radionuclides WORLD COUNCIL ON ISOTOPES

11C

(T½ = 20.4 min) and

15O

(T½ = 2.0 min), 6

both using a flow or a batch target, filled with N2 gas. Also

18F

(T½ = 1.83 h) formed in

a H218O target is removed by an online transfer after the irradiation. Most of the irradiation for radionuclide production at accelerators are, however, generally carried out using small-sized solid targets and the chemical processing is then done offline.

Some of the commonly used methods include: distillation, thermochromatography, solvent

extraction,

ion-exchange

chromatography,

electrolysis,

and

procedures

combining two or more techniques.

Quality assurance This is the last step in a chain of operations relating to the accelerator production of radionuclides. Four criteria need to be met, namely, radionuclidic purity, radiochemical purity, chemical purity and specific activity. The quality standards of radionuclides for human use are very well defined at national levels.

3. Production Methodologies and Applications Some of the commonly used medical radionuclides and their most suitable production routes at accelerators are listed in Table 1, together with the nominal batch yields achieved. They are divided into several groups according to the applications.

Standard positron emitters Short-lived radionuclides commonly used in diagnostic studies via PET are called “standard” positron emitters. They include three “organic” positron emitters, namely 11C, 15O

and

18F,

and two metallic positron emitters, viz.

68Ga

and

82Rb.

The organic

positron emitters are conveniently generated at a small-sized two particle cyclotron (Ep = 18 MeV; Ed = 9 MeV), often in the vicinity of a large clinic. For

11C

and 15O production,

generally high-pressure gas targets in batch mode are used, and GBq quantities of both are easily obtained. However, to attain high specific activity of

11C,

very special

precautions are needed. The deuteron beam is very advantageous for the production of 15O.

The production of [18F2], i.e. electrophilic

18F,

is also carried out using a gas target.

However, for removal of the activity, the addition of some F2 carrier is necessary. For WORLD COUNCIL ON ISOTOPES

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the production of

18F -, aq

enriched H218O liquid target is used and the product is obtained

in high yields of up to 400 GBq. It is utilized to produce the most commonly used PETradiopharmaceutical [18F]-2-fluoro-2-deoxy-D-glucose (2-FDG) on a large scale for routine patient care. It is estimated that worldwide about 5 million patients per year undergo diagnostic investigations using this radiopharmaceutical. Today, the whole PET technology (consisting of a cyclotron, radionuclide production unit and automated radiosynthesis apparatus) is commercially available. It is finding wide applications inoncology, cardiology and neurology. The technology is now reaching all parts of the world. It is estimated that the number of such PET centres worldwide will soon reach about 1200. In contrast to the directly produced organic positron emitters, the two short-lived metallic positron emitters, systems

68Ge/68Ga

271.0 d) and

82Sr

and

82Sr/82Rb,

68Ga

and

82Rb,

are obtained through “generator”

respectively. The parent radionuclides

68Ge

(T½ =

(T½ = 25.3 d) are produced through intermediate energy reactions;

the batch yields given in Table 1 refer to those parent radionuclides. These two radionuclides are used at PET centers, including those without a cyclotron.

Non-standard positron emitters The increasing significance of PET in medicine demanded the development of novel positron emitters with longer half-lives and different labelling chemistry than the standard positron emitters. These are needed on one the hand to investigate slow metabolic processes and, on the other, to quantify the SPECT or the therapeutic radiopharmaceutical using PET. Most of them are metals and are termed as “nonstandard” positron emitters. Some of the important ones are given in Table 1. Those radionuclides are used in immunoPET (which involves application of a monoclonal antibody labelled with a positron emitter, e.g.

89Zr,

for tumour diagnosis), theranostic

approach (which makes use of two radionuclides of the same element, a positron emitter for diagnosis and a therapeutic radionuclide, e.g.

64Cu/67Cu, 86Y/90Y,

etc.) and

bimodal imaging (which involves a combination of two imaging techniques, e.g. magnetic resonance imaging (MRI) with PET, using the radionuclide

52gMn).

Many of the

non-standard positron emitters are produced via the (p,n) reaction at a small-sized WORLD COUNCIL ON ISOTOPES

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cyclotron, mostly using a highly enriched target. The batch yields achieved are presently sufficient for most of the emerging novel medical applications, but further development work is continuing to increase the yields.

SPECT-radionuclides For the production of the listed SPECT-radionuclides, a medium-sized cyclotron of proton energy around 30 MeV is utilized. Whereas using high-current in solid targets, for

123I

67Ga, 111In

and

201Tl

are produced

a very elaborate and sophisticated gas

targetry has been developed. All the radionuclides are commercially available and find rather wide use in organ functional imaging. However, it should be pointed out that

Table 1. Common methods of production of some accelerator-based radionuclides for medical use Radionuclide

T½

Mode of decay [%]

Standard positron emitters 11 C 20.4 min O

15

18

Production route

β+ (>99.6)

14

β+ (>99.8)

14

+

18

2.0 min

N(p,α)

1.83 h

β (97); EC(3)

Ga

1.13 h

β+(90); EC(10)

1077 (3.2)

nat

Rb

1.3 min

β+(96); EC(4)

776 (13.4)

nat

Non-standard positron emitters 52g Mn 5.6 d β+(30); EC(70)

1434 (100)

82

64

Cu

12.7 h

Y I

4.18 d

β (22); EC(78)

603 (61)

124

EC(100)

185 (21.4)

68

112

225

17 → 12 →

8

Sr(p,n)

14 →

7

Y(p,n)

89

In

2.81 d

EC(100)

171 (90.7)

I

13.2 h

EC(100)

159 (83.3)

124

Tl

3.06 d

EC(100)

167 (10.0)

203

β-(100)

185 (48.6)

68

14 →

Te(p,n)

12 →

Zn(p,2n) Cd(p,2n)

Xe(p,x) Xe 123

Nid

40

SrCO3e

4

64

86

c

Y

2

TeO2e

2

Znd

50

Cdd

50

Xe

70

9 8

124

25 → 18

68

25 → 18

112

29 → 23

124

Tl(p,3n)201Pbg

28 → 20

nat

Zn(p,2p)

80 → 30

68

Pd

17.0 d

EC(100)

357 (0.02)

At

7.2 h

α(41.8); EC(58.2)

687 (0.25)

209

Ac

10.0 d

α(100)

100 (1.7)

226

Rh(p,n)

Bi(α,2n)

Ra(p,2n) 232 Th(p,x)

g

18

8

Ni(p,n)

103

211

>200 40 15

0.2

Cr(p,xn)

909 (100)

103

3

b

Crc

16 →

nat

β (22.3); EC(77.7)

Therapeutic radionuclides 67 Cu 2.6 d

100

18

70

3.27 d

201

0

RbCle

Zr

123

>100

N2(O2)a

70 → 50

86

111

N2(O2)a

70 → 20

1077 (82.5)

SPECT-radionuclides 67 Ga 3.26 d

3

Rb(p,xn)82Srf

14.7 h

+

Batch yield (GBq)

Ga(p,xn)68Gef

64

124

Target

H2 O O2(F2)a Gac

1346 (0.54)

+

8 →

O(p,n)

β+(17.8); EC(43.8), β- (38.4) β+(33); EC(67)

86 89

Energy range [MeV] 13 →

N(d,n)

F

68

a

γ-ray energy in keV (%)

13 →

7

a

Tld

50

Znd

1.5

Rhc

50

28 → 20

Bi

22 → 10

RaCl2h developing

140 → 60

226

c

5 0.5 <1

gas, b liquid, c metal, d electroplated, e pellet, f generator parent, g precursor of desired radionuclide h radioactive target

WORLD COUNCIL ON ISOTOPES

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another SPECT-radionuclide, viz.

99mTc

(T½ = 6.0 h), is more important than the above-

mentioned four radionuclides. It is obtained through the whereby the parent nuclide

99Mo

99Mo/99mTc

is produced via the fission of

235U

generator system,

in a nuclear reactor.

In recent years, considerable interest has arisen in the production of 100Mo(p,2n)99mTc

99mTc

via the

reaction at a cyclotron. The production over the energy range of Ep =

22 → 10 MeV is feasible, but the quantities produced would only suffice to meet local and regional demands. Furthermore, the problem of radionuclidic impurity needs more investigation.

Therapeutic radionuclides Therapeutic radionuclides are generally produced in nuclear reactors and many of them are routinely used in patient care. However, in recent years accelerator-based production of several therapeutic radionuclides has also been pursued, mainly to attain higher radionuclidic purity or specific activity. The production of

103Pd

and

211At

is well

established. The former is used in brachytherapy of prostate cancer and the latter in targeted alpha therapy. The methods for development. Presently the radionuclide

67Cu

225Ac

and

225Ac

production are still in

is attracting great attention with regard

to targeted alpha therapy. It is used itself and serves also as a parent for the generatorproduced

213Bi

(T½ = 45.6 min) which is an α-particle emitter, too.

4. New Developments and Future Perspectives Radionuclide production technology at accelerators for medical use is well established as far as routine patient care via PET and SPECT imaging is concerned. However, many new applications related to both diagnosis and therapy are emerging which require novel radionuclides. To meet those demands, considerable research and development work is underway, with the main emphasis on non-standard positron emitters and novel therapeutic radionuclides. The major aim is to develop internal radionuclide therapy using a β- or α-particle emitter and to quantify the dose via a PET measurement utilizing

WORLD COUNCIL ON ISOTOPES

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a suitable β+ emitter. In this regard, whereas small-sized medical cyclotrons are generally adequate for production of the novel positron emitters, the use of accelerators with proton energies between 70 and 200 MeV, for production of therapeutic radionuclides like

67Cu, 117mSn, 223Ra, 225Ac,

etc. is increasing. Two further concepts are

also developing: (1) the utilization of hard photons generated at 40 MeV electron LINAC to produce radionuclides like

67Cu

via the

68Zn(γ,p)-reaction.

(2) the use of a 40 MeV

d(Be) or d (C) breakup neutron source at an accelerator to produce β- emitting radionuclides via the (n,p) or (n,np) reaction (e.g.

67Cu).

In short, the science and

technology of medical radionuclide production at accelerators is a fast expanding and thriving field. It entails fundamental as well as applied areas of research which are both challenging and rewarding. The future perspectives of this field of work thus appear to be very promising.

Further reading 

S.M. Qaim: The present and future of medical radionuclide production. Radiochimica Acta 100 (2012) pages 635-651.



S.M. Qaim, B. Scholten, B. Neumaier: New developments in the production of theranostic pairs of radionuclides. J. Radioanal. Nucl. Chem. 318 (2018) pages 1493-1509.



S.M. Qaim: Medical Radionuclide Production – Science and Technology. De Gruyter, Berlin/Boston, (2019) pages 1-288. ISBN 978-3-11-060156-5.

To Contents

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02. Isotope-related News ARTMS to advance ImmunoPET Imaging Isotope with Funding Support from Innovate BC ARTMS Inc., a global leader in the development and commercialization of novel technologies and products enabling cyclotron production of the world’s most needed medical radioisotopes, announced that it received $300,000 funding from Innovate BC as part of its Ignite program. The funding will be combined with over $600,000 from additional sources to further develop and validate the production of zirconium-89 (Zr89) for use in Positron Emission Tomography (PET) imaging scans of cancer patients eligible for immuno-oncology (IO) therapies.

The overarching goal of this project is to utilize the ARTMS’ proprietary QUANTM Irradiation SystemTM (QISTM) hardware system and expertise in solid targetry to produce high-quality and high-activity Zr-89 for the radiolabeling of molecular targeting ligands, such as antibodies, which are used in the non-invasive monitoring of the immune system by Immuno-Positron Emission Tomography.

To read more please visit: https://zh.dotmed.com/news/story/54173 Source: Health Care Business News

Diamond Batteries Promise to Power Space Probes for 100 years Diamond batteries capable of generating electricity for 100 years are being considered for use in space probes and in equipment for underground mining. These batteries use man-made diamonds that generate electricity when placed in a radioactive field. If radioactivity can be controlled and blocked by wrapping these batteries in aluminum or other metal sheets, they can then be put to use.

The research group at NIMS (National Institute for Materials Science, Japan) used WORLD COUNCIL ON ISOTOPES

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electrons, adopted by devices such as electronic microscopes, instead of beta rays for the production of electricity, but it plans to use nickel-63 from now on.

To read more please visit: https://asia.nikkei.com/Business/Technology/Diamond-batteries-promise-to-powerspace-probes-for-100-years Source: NIKKEI Asia

Fusion Pharmaceuticals to Expand Pipeline with Acquisition of IPN1087, a Small Molecule Targeting NTSR1, from Ipsen Fusion Pharmaceuticals Inc. (Nasdaq: FUSN), a clinical-stage oncology company focused on developing next-generation radiopharmaceuticals as precision medicines, today announced it has entered into an asset purchase agreement (APA) to acquire Ipsen's (Euronext: IPN; ADR; IPSEY) intellectual property and assets related to IPN1087. IPN-1087 is a small molecule targeting neurotensin receptor 1 (NTSR1), a protein expressed on multiple solid tumor types. Fusion intends to use IPN-1087 to create an alpha-emitting radiopharmaceutical, FPI-2059, targeting solid tumors expressing NTSR1.

To read more please visit: https://www.newswire.ca/news-releases/fusion-pharmaceuticals-to-expand-pipeline-withacquisition-of-ipn-1087-a-small-molecule-targeting-ntsr1-from-ipsen-884009654.html Source: Fusion Pharmaceuticals Inc.

Electrochemical Plant's Revenue from Stable Isotopes rises by 14% Electrochemical Plant (ECP), a subsidiary of Rosatom's nuclear fuel manufacturer TVEL, recorded a 14% increase in revenue from the sale of stable isotopes in 2020, exceeding RUB1.5 billion (USD20.1 million) for the first time. The Zelenogorsk, Krasnoyarsk-based company's global market share of the stable isotope market remains over 40%, TVEL said.

WORLD COUNCIL ON ISOTOPES

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ECP produces 110 isotopes of 21 chemical elements for use, among other fields, in the nuclear power, medical and electronics sectors, as well as for scientific research in chemistry, physics, biotechnology, meteorology and agricultural chemistry. Its global reach extends to, for example, to Canada, China, Germany, France, Kazakhstan, South Korea, Sweden, the USA and Uzbekistan. Most of ECP's export contracts for stable isotopes are signed through Isotope JSC, Rosatom's subsidiary for isotope sales and marketing.

To read more please visit: https://world-nuclear-news.org/Articles/Rosatom-revenue-from-stable-isotopes-rises-by-14 Source: WNN

Proposals for First FRIB Experiments Align with National Priorities, Span Full FRIB Capabilities As the Facility for Rare Isotope Beams (FRIB) readies to commence user operations in early 2022, scientists submitted experiment proposals in response to FRIB’s first call for proposals.

Eighty-two proposals requesting 9,784 hours of beam time and six letters of intent were submitted, covering 16 of the 17 National Academies benchmarks for FRIB. These proposals align with national science priorities and span the four FRIB science areas: properties of rare isotopes; nuclear astrophysics; fundamental interactions; and applications for society, including in medicine, homeland security, and industry.

The proposals request the full spectrum of FRIB’s capabilities: fast, stopped, and reaccelerated rare-isotope beams, use of all FRIB experimental areas offered in the first Program Advisory Committee (PAC), as well as all major FRIB instruments.

To read more please visit: https://frib.msu.edu/news/2021/PAC1-proposals.html Source: FRIB at Michigan State University WORLD COUNCIL ON ISOTOPES

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Pure

Promethium:

ORNL

Extracts

in-demand

Isotope

from

Plutonium Leftovers A new method developed at Oak Ridge National Laboratory proves that one effort's trash is another's valuable isotope. One of the byproducts of the Department of Energy lab's national plutonium-238 production program is promethium-147, a rare isotope used in nuclear batteries and to measure the thickness of materials.

It's difficult and costly to dispose of waste containing radioactive elements left over after neptunium-237 targets are irradiated in the High Flux Isotope Reactor, a DOE Office of Science user facility, to produce Pu-238 for space exploration. But last year, a new ORNL project for the DOE Isotope Program began mining Pm-147 from the fission products left when Pu-238 was separated out of the target.

This effort's primary goal is to reestablish domestic production of Pm-147, which is in short supply, and it has a side benefit: reducing the concentrations of radioactive elements in the waste, so that it can be disposed of safely in simpler, less expensive ways both now and in the future.

To read more please visit: https://apnews.com/Business%2520Wire/d9f703132903473989ab0203395b8d7b Source: EurekaAlert

Petten Reactor Switches to Low Enriched Uranium The Nuclear Research and Consultancy Group (NRG) in the Netherlands said on 18 March that, from now on, the High Flux Reactor (HFR) in Petten will only produce medical isotopes using low enriched uranium (LEU). Until recently, production for NRG's Belgian partner IRE was still based on highly enriched uranium (HEU), because IRE could not fully process low-enriched uranium. However, IRE has now partially converted its chemical process to LEU allowing NRG to take the final step and end the use of HEU

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in the HFR. Every day, 30,000 patients worldwide are treated with medical isotopes from the Petten reactor. In 2006 the reactor switched from HEU to LEU fuel. In 2018, NRG, together with Curium, took the step to also convert the molybdenum-99 production process in the Pettense Molybdenum Production Facility (MPF) to LEU. "We are extremely pleased that the final step has been taken with this and that our partners no longer need highly enriched uranium for the production of medical isotopes from the HFR," said Vinod Ramnandanlal Commercial Director NRG. "In fact, in this way we achieve a kind of nonproliferation quality mark for medical isotopes."

To read more please visit: https://www.neimagazine.com/news/newspetten-reactor-switches-to-low-enricheduranium-8616762 Source: Nuclear Engineering International Magazine

New System may offer Improved Options for Cancer TreatmentLANL Radioisotopes are a key weapon in the medical arsenal for treating cancer. Most treatments use beta-particle-emitting isotopes to destroy cancer cells. Alpha particles can do a better job, says Los Alamos National Laboratory. It announced that improved options for cancer treatment are on the way, thanks to a new system developed at Los Alamos National Laboratory for producing alpha-emitting medical radioisotopes intended to target and overpower diseased tissue while sparing the healthy tissue around it.

To read more please visit: https://www.news-medical.net/news/20210311/New-system-may-offer-improvedoptions-for-cancer-treatment.aspx Source: Los Alamos National Laboratory WORLD COUNCIL ON ISOTOPES

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BWXT and GMS set up Joint Venture to supply Radioisotopes to Asia-Pacific Region US-based BWXT Medical Ltd. and Global Medical Solutions Ltd. have entered into a joint venture to manufacture and distribute radioisotopes and radiopharmaceuticals in the Asia-Pacific, BWXT said on 8 March. BWXT Medical is a global supplier of medical isotopes

and

radiopharmaceuticals.

GMS

is

a

global

operator

of

centralized

radiopharmacies, a manufacturer and distributor of diagnostic and therapeutic radiopharmaceuticals, diagnostic imaging equipment, medical devices and services.

To read more please visit: https://www.neimagazine.com/news/newsbwxt-and-gms-set-up-joint-venture-tosupply-radioisotopes-to-asia-pacific-region-8592047 Source: Nuclear Engineering International Magazine

IBA and NorthStar Medical Radioisotopes Expand Collaboration to Enable Global Availability of Diagnostic Radioisotope Technetium-99m IBA (Ion Beam Applications), the world’s leading provider of proton therapy solutions for the treatment of cancer, and innovator

in

the

NorthStar Medical Radioisotopes, LLC, a global

development,

production

and

commercialization

of

radiopharmaceuticals used for medical imaging and therapeutic applications, today announced a collaboration to increase global availability of technetium-99m, the most widely used medical radioisotope. The collaboration enables companies outside of the United States to access the Tc-99m Generation Systems that utilize NorthStar’s proprietary non-uranium based Mo-99 produced using IBA’s accelerators and beamlines.

To read more please visit: https://www.iba-radiopharmasolutions.com/iba-and-northstar-medical-radioisotopesexpand-collaboration-enable-global-availability-diagnostic Source: IBA

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Jubilant Radiopharma and Isotopia Molecular Imaging Enter into a Strategic Partnership to Further Advance the Field of Radiotherapeutics Isotopia Molecular Imaging Limited (Isotopia, Israel) and Jubilant Radiopharma, a business division of Jubilant Pharma Limited (USA), have entered into a strategic commercial partnership. Under the terms of the partnership, Jubilant Radiopharma, together with Isotopia, will increase their portfolio of products and expand their commercial footprint in North America - the largest market for Nuclear Medicine procedures in the world.

To read more please visit: https://www.pharmiweb.com/press-release/2021-03-16/jubilant-radiopharma-andisotopia-molecular-imaging-enter-into-a-strategic-partnership-to-further-ad Source: PharmiWeb

Japan Scientists separate Oxygen Molecules used in PET Japanese researchers have discovered that nanoporous carbon can separate the isotope oxygen-18 (O-18) from oxygen-16 (O-16), which is an essential isotope for producing Fluorine-18 (F-18) the most used radionuclide in PET diagnosis. When a mixture of O16 and O-18 is introduced into the nanoporous carbon, the O-18 is preferentially adsorbed and separated from O-16, according to a research team led by Katsumi Kaneko of the Research Initiative for Supra-Materials (RISM) at Shinshu University (Nature Communications, January 22, 2021). The researchers were also able to separate O-18 from O-16 using the low-temperature waste heat from a natural gas storage facility.

To read more please visit: https://www.auntminnie.com/index.aspx?sec=log&URL=https%3a%2f%2fwww.auntminnie.co m%2findex.aspx%3fsec%3dsup%26sub%3dmol%26pag%3ddis%26ItemID%3d131624 Source: AuntMinnie

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18

ITM Enters Global Supply Agreements with Telix Pharmaceuticals for Clinical and Commercial Use of ITM’s n.c.a. Lutetium-177 ITM

AG

(Isotopen

Technologien

Munchen,

Germany),

a

privately

held

radiopharmaceutical biotech company, announced today that is has signed two strategic agreements with Telix Pharmaceuticals Limited for the global supply of ITM’s highly pure therapeutic radioisotope no-carrier-added Lutetium-177 (n.c.a. 177Lu). ITM’s n.c.a.

177Lu, known under the brand name EndolucinBeta®, is a high-purity version of the beta-emitting radioisotope Lutetium-177 that can be linked to a variety of tumorspecific targeting molecules for Targeted Radionuclide Therapy and has demonstrated significant anti-tumor effects in clinical and commercial use.

To read more please visit: https://www.streetinsider.com/Business+Wire/ITM+Enters+Global+Supply+Agreeme nts+with+Telix+Pharmaceuticals+for+Clinical+and+Commercial+Use+of+ITM%E2% 80%99s+n.c.a.+Lutetium-177/18145009.html Source: StreetInsider

The Construction of the RECUMO Plant is now One Step Closer As of the end of March, 2021, a public enquiry would have been held into the construction of the RECUMO plant on the SCK CEN site in Mol. In the proposed plant, the research centre will purify the radioactive residues resulting from the production of medical radioisotopes. “Radioisotopes of that type are indispensable in the fight against cancer and other diseases and thanks to this installation, we can guarantee their supply.

The public enquiry forms an important step in the realisation of the RECUMO project,” said Eric van Walle, Director-General of SCK CEN. To read more please visit: https://www.sckcen.be/en/news/construction-recumo-plant-now-one-step-closer Source: SCK CEN

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Americium-241: Domestic U.S. Supply Available For the last 20 years Americans have relied on a single foreign supplier for the active ingredient used in smoke detectors. The DOE Isotope Program has addressed this isotope shortage and was pleased to announce the re-established routine supply of americium-241 (Am-241). The isotope is vital for a variety of additional applications like oil and gas exploration and moisture gauges.

To read more please visit: https://www.isotopes.gov/americium241 Source: National Isotope Development Center

To Contents

WORLD COUNCIL ON ISOTOPES

20

03. Sketches from the WCI Secretariat 3-1. The WCI Secretariat solicits its Members’ Profiles and Isotope Technologies for Technology Transfer among the WCI Members Enabling the Sharing of Information for the Peaceful Uses of Isotope Technologies 1. Backgrounds: - The WCI has the mission to promote the safe and environmentally sound use of isotope technologies for global well-being. It is also keen to promote the sharing of information on the peaceful uses of isotope technologies among the WCI members.

- The WCI cooperates actively with other regional and international organizations to promote the peaceful applications of isotope technologies.

2. Role of the WCI: - The WCI will introduce the WCI members’ profiles and useful isotope technologies for technology transfer among the WCI members, enabling the sharing of information for the peaceful uses of isotope technologies through the WCI newsletter and homepage.

- The WCI will upload this information on the WCI website (www.wci-ici.org) for WCI members to access after the WCI releases the monthly newsletter. WCI does not bear any responsibility for errors in the information posted by the WCI member. * On this matter, please visit the WCI website (www.wci-ici.org), and apply for the WCI membership. * It is noted that information related to technology transfer can only be viewed by the WCI members.

3. Role of the WCI Members: - The WCI members cooperate in providing information about their profiles and isotope technology description requested by the WCI Secretariat.

- Each WCI member who has provided technical information is responsible for monitoring the relevant information and taking appropriate action on legal arrangement/issues related to technology transfer.

- Technology transfers can be finalized through mutual understanding of the benefits between the technology transferee and transferor. Any WCI member interested in conducting a technology transfer has to make contact with any chosen counterpart WORLD COUNCIL ON ISOTOPES

21

for the sound transfer of technology.

4. Expected Benefits/Outcomes: - The WCI will help share the information on the peaceful uses of isotope technologies and promote technology transfers for and to businesses among the WCI members through the WCI newsletter and homepage, as part of undertaking the implementation for its mission.

- The WCI members will promote their business profiles, including technologies, products, and services, and take the opportunity to sell and buy isotope technologies for the peaceful uses between the technology transferors and transferees through their own technology transfer mechanisms in a cost-effective and efficient manner.

5. How to Submit and Release: - The WCI members (individuals and organizations) wishing to transfer technologies are cordially requested to complete the attached form and submit it to the WCI Secretariat (secretary@wci-ici.org) by the 25th of each month.

- Format: 

Sample format is given below, modification is allowed except for any changes in numerical order.



All contents should be written in English.



The length of article should be within 2 pages.

(A4, Times New Roman with 12 font size and 1 line space)



Images may be included.

- The WCI will release this article on a first come first served basis.

6. Donation to the WCI - The minimum amount for donation is USD 1,000.

- Your financial support to the WCI will promote the safe and environmentally sound use of isotope technologies for global wellbeing through the WCI activities.

7. Inquiry If you have any inquiries on this article, please contact secretary@wci-ici.org.

WORLD COUNCIL ON ISOTOPES

22

[Attachment] The WCI member's profile and isotope technologies for technology transfer (Sample) [Name of Company/Institute] Photo (optional)

1. About us (Brief introduction of company/institute) (sample) The World Council on Isotopes (WCI) was founded in 2008 and has a fast-growing and highly diverse membership, representing a broad range of interests and perspectives of the R&D, business, industrial, and governmental sectors.

2. Isotope Technologies for major Products/Services you offer (Isotope technologies for primary products or services of company/institute) (free format)

3. Technology Transfer [selling( ), buying( ), or others(specify)] (describe the technologies you wish to transfer) (free format)

4. Contact Detail 

Homepage : www.wci-ici.org



e-mail : secretary@wci-ici.org



(add more details if necessary)

*note below will not be included on article.

(Note) The donation to the WCI will be: (identify the amount of donation to the WCI) (sample) USD 1,000.00

WORLD COUNCIL ON ISOTOPES

23

3-2. The WCI Secretariat has launched its Facebook Page for

Better Communication with its Members and the World’s people

The

WCI

Secretariat

has

launched

a

WCI

Facebook

presence

to

expediate

communication with its members and the world’s people. The WCI secretariat will provide regular updates on WCI activities, via its Facebook page, on various matters including

its

newsletter,

announcements,

training

courses

and

International

Conferences on Isotopes (ICI). Be sure to follow and/or like our uploads.

The WCI Facebook account is www.facebook.com/WorldCouncilonIsotopes.

To Contents WORLD COUNCIL ON ISOTOPES

24

04.Future Conferences and Events 2021 SNMMI Annual Meeting • Date: June 11 – 15, 2021 • Venue: Virtual • Website: https://am.snmmi.org/iMIS/SNMMI-AM The SNMMI 2021 Annual Meeting is recognized as the premier educational, scientific, research, and networking event in nuclear medicine and molecular imaging. The four-day event, taking place each June, provides physicians, technologists, pharmacists, laboratory professionals, and scientists with an in-depth view of the latest research and development in the field as well as providing insights into practical applications for the clinic.

IRRMA 2021 • Date: July 4 – 9, 2021 • Venue: Moscow, Russia • Website: http://www.lnf.infn.it/conference/irrma2021/ The

International

Topical

Meeting

on

Industrial

Radiation

and

Radioisotope

Measurement Applications (IRRMA) is a triennial event organized for the purpose of bringing together scientists and engineers from around the world who share an interest in radiation and radioisotope measurement applications.

ARIS 2021 • Date: September 5 – 10, 2021 • Venue: Palais des Papes, Avignon, France • Website: https://indico.in2p3.fr/event/19688/ ARIS 2021, the fourth international conference on Advances in Radioactive Isotope Science (ARIS), will be held in France's beautiful city of Avignon from 5-10 September 2021. ARIS is the flagship conference for rare isotope science, born from the merger of the international conferences ‘Exotic Nuclei and Atomic Masses’ and ‘Radioactive Nuclear Beams’.

WORLD COUNCIL ON ISOTOPES

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34th Annual Congress of the European Association of Nuclear Medicine • Date: October 23 – 27, 2021 • Venue: Hamburg, Germany • Website: https://www.isotopes.gov/node/431 With more than 150 sessions, the EANM Annual Congress is the most valuable nuclear medicine gathering worldwide. Each year, more than 6,200 participants have the possibility to network, socialize and discuss the newest trends and findings in the field of nuclear medicine. The EANM is proud of receiving approximately 2,200 abstracts annually from all over Europe and around the world. 160 exhibiting companies, covering an area of 3,500 sqm present their newest technologies.

Advanced PET Imaging, Nuclear Medicine, and Therapy: From Diagnostics to Theranostics • Date: November 4 - 6, 2021 • Venue: Las Vegas, USA • Website: https://www.petctcme.com/las-vegas-november-2021/ This course provides a clinical perspective on PET/CT imaging and the emerging use of Theranostic agents within Nuclear Medicine. A broad perspective on the economic, clinical, and academic aspects of the latest trends in PET/CT imaging and nuclear medicine therapy will be presented.

At the conclusion of this course, participants will be able to: ✓ Describe new developments in the merger of diagnostic and therapeutic radio ligands for PET/CT imaging and therapy with specific focus on DOTA, PSMA, and PRRT. ✓ Describe the logistics of bringing these new diagnostic and therapeutic technologies into clinical practice. ✓ Identify

the

key

clinical

indications

for

new

emerging

tracers

for

the

neuroendocrine tumor and prostate cancer using a somatostatin receptor and

WORLD COUNCIL ON ISOTOPES

26

PSMA PET/CT imaging. ✓ Review and discuss the standard-of-care clinical application and advanced interpretation of FDG PET/CT.

NESTet (Nuclear Education and Training) 2021 • Date: November 14 - 18, 2021 • Venue: Brussels, Belgium • Website: https://www.euronuclear.org/nestet2021/ NESTet is the most important European forum discussing opportunities and challenges in nuclear

education, training,

knowledge

management and human resource

development related to nuclear energy and other nuclear applications. The 2021 edition will bring together nuclear stakeholders, including policy and decision makers, educators, training providers, employers and human resource managers. Our young generation – incoming nuclear professionals from all over Europe – will be there to challenge the established views and enrich the discussion!

12th IsoEcol • Date: June 6 – 10, 2022(tentative) • Venue: Gaming, Austria • Website: https://sites.google.com/view/isoecol2020/ The 12th International Conference on the Applications of Stable Isotope Techniques to Ecological Studies (IsoEcol) will be held in the beautiful town of Gaming, Austria, organized

by

the

Inter-University

Center

for

Aquatic

Ecosystem

Research

WasserClusterLunz in cooperation with the International Atomic Energy Agency (IAEA) from June 20-26, 2021. The conference venue is at the historic Kartause (Charter house) in Gaming (pronounced Gah-ming), approximately 2 hours from Vienna by car or public transportation.

WORLD COUNCIL ON ISOTOPES

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Astrophysics with Radioactive Isotopes (AwRI) 2022 • Date: June 12 – 17, 2022 • Venue: Budapest, Hungary • Website: https://indico.cern.ch/event/820113/ Radioactive nuclei play a significant role in many current astrophysical pursuits, from the origins of the elements to the driving of emissions from supernovae ( 56Ni) and kilonovae (r-process radioactivity). Radioactive nuclei are crucial for direct studies of galactic enrichment (7Be,

26Al, 44Ti, 60Fe, 99Tc, 244Pu)

and stellar explosions (56Ni,

44Ti).

Stars and their explosions, galaxies and their evolving interstellar medium, and the origins of the solar system are among the targeted astrophysical objects. Stardust, meteorites, ocean floor deposits, cosmic-rays, and gamma-ray spectroscopy provide a rich variety of astronomy to exploit having their inherent power of radioactivity.

Investigation tools range from numerical models, astronomical instrumentation, and laboratory experiments to derive material compositions and nuclear reaction rates. The aim of the conference is to bring together researchers from all of these different fields to promote interaction through the common ground of radioactivity.

11th International Conference on Isotopes (11ICI)

• Date: June 19 – 23, 2022 • Venue: Saskatoon, Saskatchewan, Canada • Website: https://www.11ici.org/ WORLD COUNCIL ON ISOTOPES

28

11ICI hosted by Sylvia Fedoruk Canadian Centre for Nuclear Innovation (the Fedoruk Centre) in partnership with the University of Saskatchewan and Tourism Saskatoon, will build on past conferences by continuing a multifaceted interdisciplinary exchange between the developers and producers of isotopes and apply isotopes in medicine, industry, agriculture, national security and other fields. Selected papers will be published on a special issue of the Journal of Radioanalytical and Nuclear Chemistry (JRNC). The ICI conferences have been held since 1995, recently every two years. They are organized by the World Council on Isotopes (WCI) and a participating organization to highlight the importance of nuclear science, medicine, and technology in advancing human health and protection of the environment.

Second International Conference on Applications of Radiation Science and Technology (ICARST-2022) • Date: August 22 - 26, 2022 • Venue: Vienna, Austria • Website: https://www.iaea.org/events/icarst-2022 The Second International Conference on Applications of Radiation Science and Technology, which was planned to be held at the IAEA headquarters in Vienna, Austria, from 19 to 23 April 2021 has been postponed due to the COVID pandemic. It is now going to be held from 22 – 26 August 2022.

ICARST-2021 will cover a variety of topics related to the applications of radiation technologies in fields as diverse as industry, medicine, materials science, engineering, biology, physics and chemistry. The conference will serve as a platform for fostering new initiatives among industry and academia, establishing new and strengthening existing collaborations and identifying best practices as well as raising awareness among decision makers on how radiation technologies can be applied to meet global challenges.

To Contents WORLD COUNCIL ON ISOTOPES

29

My Biz on Isotopes Call for Articles As the WCI monthly newsletter is the most important communication channel for the dissemination of information to members and other interested parties, we would like to add a new section ―‘My Biz on Isotopes’ to our newsletter. This new section will be dealing with business opportunities in the field of isotope related technologies.

1. Purpose The purpose of this section is to foster communication and to provide members with opportunities to raise their organization’s profile.

2. Requirements The article provider should be a member of the WCI. (To join us, please visit www.wciici.org and sign up online. There is no membership fee.) The writer should be a professional working in the field of isotope production or in the application of isotopes or radiation.

3. Contents Your article may include topics that demonstrate the cross-cutting and interdisciplinary technologies of your organization.

Topics and areas of contents may include but are not limited to: 

A short introduction of your organization (status, field of business, location)



The advantages/strengths of your technology



The future plans of your organization



Other topics of relevance, e.g. interest in collaboration or joint research, joint investment, or technology transfers.

WORLD COUNCIL ON ISOTOPES

30

4. Format 

All articles should be written in English.



The length of article should be within 4 pages (A4, Verdana with 10 font size and 1.5 line.



Images may be included.

All submissions meeting the above requirements should be submitted to secretary@wciici.org 5. Deadline Articles that are received by the WCI Secretariat via email by the 25th of the month will be considered for the next month’s newsletter.

6. Others The WCI Publication Committee Chair will review articles for possible inclusion in our newsletter. Articles might be edited according to our own format. The WCI Secretariat will not make any payment for submitted articles.

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