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ABSTRACT

This paper reviews efforts on using high energy (25 – 30 MeV) and highpower (10-20 kW) electron linacs and lower energy (7 MeV) protonlinacs for medical radioisotope production. Using high energy x-raysfrom the electron linacs, PET (Positron Emission Tomography)radioisotopes are produced through photonuclear reactions such as19F(γ,n)18F, which also allow production of other PET radionuclides 11C,13N, and 15O. Other mostly used medical radionuclides 99mTc can alsobe obtained by using the electron linacs, through photofission orphotonuclear reactions. Proton linacs for PET have also been recentlydeveloped and the product has been available in the market since 2005.The linacs have been tested for 18F production. As a proton accelerator,the target systems and nuclear reactions are similar to the ones used inPET cyclotrons.

Keywords: electron linacs, proton linacs, photonuclear, photofission, medical radioisotopes

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INTRODUCTIONElectron linacs → high energy electron beam → cancer treatment (directlyor converted to high energy photon for gamma therapy)Nuclear reactors (by neutron irradiation) → 99mTc for SPECT (Single

Photon Emission Computerized Tomography) diagnosticsCyclotrons → 18F for PET (Positron Emission Tomography) diagnostics

→ use enriched 18O(p,n)18F (t½ = 110 menit)

Electron linacs → high energy (25-30 MeV) and high power (10-20 kW) →photonuclear reactions 19F(γ,n)18F → use natural 19F (100%) as target

also 12C(γ,n)11C, 14N(γ,n)13N, 16O(γ,n)15O (PET)100Mo(γ,n)99Mo → 99mTc, 100Mo (9,63%)(SPECT)

→ electron linacs for production of radionuclides for diagnosticsand gamma therapy

Proton linacs (7 MeV, developed by AccSys Technology, Inc., Hitachi'ssubsidiary company, available since 2005) → target system is similar toPET cyclotron → saves the weight (14-18 tons) and complexity ofcyclotron magnet

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citra PET

Sintesis FGD

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ELECTRON LINACSPET RadionuclidesPhotonuclear cross sections yielding 15O, 13N, 11C from natural isotopes allpeaks at about 25 MeV of photon energy.

18F ~ 106 Bq/g or 102 μCi per μA of linac electron beam current usingphotonuclear reactions at 25 MeV.A. N. Dovbnya et al. “Production of Short-Lived Radionuclides on the ElectronLinac for PET” in Problems in Atomic Science and Technology 3 (1999) 105.

IAEA-TECDOC-Draft No 3, “Handbook on photonuclear data for applications.Cross sections and spectra,” March 2000.

(t½ = 2 menit)

(t½ = 20,4 menit)

(t½ = 10 menit)

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Table 1. Specific activities (in Bq/g per μA of linac electron beam current) of some PET radionuclides obtained by using photonuclear reactions at 25 MeV.

Radio-nuclide

Mac Gregor (1957) Lutz (1969) Dovbnya et al. (1999)

11C 9.25 106 5.30 106 1.90 106

13N 3.76 106 1.04 106 1.67 106

15O 3.20 106 8.40 106 2.50 106

18F 2.04 106 2.12 106 1.70 106

Table 2. Comparative data on production of 15O at various electron linacs.Data on Center of Nuclear

Medicine, Cincinnati, USA (1982)

Kurchatov, IAE, Moscow (1985)

NSC KIPT, Kharkov

Irradiation conditions

E0 = 26 MeVIav = 100 μATirr = 4 min V = 500 cm3

E0 = 30 MeVIav = 100 μA Tirr = 7 min V = 200 cm3

E0 = 25 MeV Iav = 300 μA Tirr = 10 min V = 200 cm3

Integral activity

184 mCi(6.8 109 Bq)

700 mCi(25.9 109 Bq)

130 mCi(4.8 109 Bq)

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Advantage:Target for photon irradiations•simpler in preparation•no direct beam heating (borne by target converting electron beamenergy into photons at up to about 50% efficiency)•naturally abundant isotopes (isotopic enrichment not required)•utilize high penetrability of photons

Drawbacks:

•Higher energy (20-30 MeV)•Photonuclear cross sections are one to two orders smaller (1/10 to1/100) than those of nuclear reactions of proton or deuteron.

15O

e

γp

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Non-PET/SPECT Medical Radionuclides40 million nuclear medicine procedures/year → 80% use 99Mo.99Mo traditionally manufactured using nuclear reactors to irradiatehighly enriched uranium (HEU) targets. The Canada’s NationalResearch Universal (NRU) reactor at Chalk River → produces abouthalf of the world’s supply, operating since 1957 → suffered age-relatedshutdowns.→ photons from a high-power electron linear accelerator to produce99Mo from natural uranium through photonuclear reaction

γ + 238U → 99Mo + 13xSn + 2D + ….. The radiochemistry to recover and refine the 99Mo generated throughphotofission from natural uranium target is similar to that which iscurrently in use for reactors using highly enriched uranium targets.Canada’s five-year plan (2010–2015, Advanced Rare IsotopeLaboratory/ARIEL Project) for TRIUMF includes the construction andoperation of a high-power (50 MeV, 10 mA) electron linear accelerator.A single multimegawatt machine could supply the entire Canadianmarket or 5–7% of the total North American market.

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Another approach at Yerevan Physics Institute (YerPhI) in Armenia isto use 100Mo target (9,63% natural) through photonuclear reactionγ + 100Mo → 99Mo + n, 99Mo (T½ = 67 hours) → 99mTc (T½ = 6 hours)

with threshold of reaction at 9.1 MeV. Unlike uranium target, thisapproach gives high purity isotopes and free from other radioisotopeswhich otherwise should be removed as wastes. The project wasstarted at 2006 with collaborators from University of BritishColumbia/TRIUMF, Canada (Canadian Light Source/CLS Project,funded since 2010).To produce 99mTc, the existing linear high current electron accelerator(I = 250 μA and E = 20 MeV) at YerPhI was used to irradiate a 20 gtarget of enriched 100Mo for 100 hours to produce approximately 20-40Ci of 99mTc isotope, which correspond to about 5 Ci or 1.85 1011

Bq/day. This amount would satisfy the requirements of Armenia andneighboring regional countries. Once it is successfully proven, enoughradioisotopes could be provided for direct use in Armenia as well as forpotential clients (according to list of IAEA).

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CLS – Canadian Light Source Project, funded since 2010

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ION LINACSPET RadionuclidesSince 2005 Hitachi, Ltd. and AccSys Technology, Inc. (Hitachi'ssubsidiary company) manufactured a linear accelerator-based systemfor PET radiopharmaceuticals production. The AccSys PULSAR® − 7is a radiofrequency linear proton (H+) accelerator system for PETradionuclide production. It consist of H+ duoplasmatron ion source (30keV), radiofrequency quadrupole (RFQ) → 1st stage accelerator (up to3.5 MeV), drift tube linac (DTL) → 2nd stage accelerator (up to 7MeV), shielded PET radionuclide target system, and a PC-basedcontrol system → sufficient to produce PET radionuclide 18F.

16 m

3 ton

9 ton

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August - September 2006 Wisconsin Medical Cyclotron (WMC) facilityin West Allis, Wisconsin, tested PULSAR® − 7 in a mobileconfiguration. On-board equipment included a radiopharmaceuticalsynthesis module (GE MXFDG) in a shielded mini-cell, a completequality testing laboratory, and patient dose preparation equipment.Drift tube linac → pulsed beam of 125 μs length at 85 Hz repetitionrate, 9 mA, 1% duty cycle. Target system → support grid on titaniumtarget window for cooling and support (about 315 psi), transmission ofbeam → 65%. Thin target with 0.35 ml H2

18O → 18F 634 mCi/h, 1068mCi/2h, similar fixed/not mobile unit → 1 Ci/hour → mobile systemmarginal chiller restricted power to lower beam current → interruptedbombardment → cooling system was later rebuilt, beam alignmentslightly offset → < 65% beam transmission through grid.The trial demonstrated the mobile proton linac unit to achieve a 94%18F production batch reliability, to perform multiple daily bombardmentsof several hours, to produce 18F suitable for [18F] FDG manufacture forsmall scale distribution, and the product met quality standard.

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CONCLUSION

The electron and proton linear accelerators have been proven tohave feasibility for medical isotope production, which at presentmostly produced commercially by using cyclotrons or nuclearreactors.For the electron accelerators, however, due to lower crosssections and higher energy thresholds, further efforts are stillunderway to prove that it is commercially feasible.As for the proton linear accelerators, fixed and mobile compactmodels have been developed and commercially available,providing more choices other than compact or baby cyclotrons,which could be considered for installation.

Electron linac Proton linac CyclotronEnergy, ion 20-30 MeV, e 7 MeV, H+ 5-18 MeV, H−

Magnet no/… no/12 ton yes/14-18 tonsRadioisotopes PET F, O, N, C) &

SPECT ( Mo/99mTc)PET

( F, O, N, C)PET

( F, O, N, C)