Photon, neutron and proton induced reactions to

produce medical isotopes (CRP-Project No. 17443/R0)

BY

H. Naik1, G.N. Kim2, S.V. Suryanarayana3 & M.S. Murali1

1. Radiochemistry Division, BARC

2. Kyungpook National Univ., Korea

3. Nuclear Physics Division, BARC

AND

Dr. Roberto Capote Noy

Division of Physical and Chemical Sciences, IAEA, VIENNA

SUMMARY OF RESEARCH CONTRACT No. 17743/R0

- Study of production of medical isotopes using photon, neutron and charged particle induced nuclear reactions is important for medical application.- This project explores the feasibility of medical isotopes production using accelerators, circumventing the need for nuclear reactors.

- Production and estimation of following reaction products (a) Production of 99Mo-99mTc from the 100Mo(,n)99Mo,

238U(γ,f)99Mo reactions and their radiochemical separation(b) 68Zn(,p)67Cu reactions(c) Production of 32P, 33P and 47Sc from the 32S(n,p)32P, 33S(n,p)33P, 47Ti(n,p)47Sc reactions

(d) Production of 68Ga from the 68Zn(p,n)68Ga reaction

(a) 92Mo(14.84%), 94Mo( 9.25%), 95Mo(15.92%), 96Mo(16.68%), 97Mo(9.35%), 98Mo(24.13%), 100Mo(9.63%)

100Mo(γ,n) 99Mo-99mTc reactionEth =8.29 MeV

(b) 238U (99.3%), 235U (0.7%) 238U(γ,f) 99Mo-99mTc reaction No Eth

Feasibility above Eγ of 5 MeV

(c) 32S(95.02%), 33S (0.75 %), 34S (4.2 %) and 36S (0.02 %) 32S(n,p)32P reaction Eth = 0.957 MeV 33S(n,p)33P reaction No Eth

(d) 46Ti(8.0%), 47Ti(7.5%), 48Ti(73.7%), 49Ti(5.5%), 50Ti(5.3%), 47Ti(n,p)47Sc reaction No Eth (e) 64Zn(48.6%), 66Zn(27.9%), 67Zn(4.1%), 68Zn(18.8%), 70Zn(0.6%) 68Zn(p,n)68Ga reaction Eth = 3.76 MeV

IMPORTANCE OF THESE PROPOSED MEDICAL ISOTOPES

-About 3000 isotopes are available from natural and/or from artificially prepared sources.

-140 radioisotopes among 3000 of isotopes are used worldwide in medical applications such as diagnostic, therapeutic and preventive purposes [1].

-Out of the 140 radioisotopes from only 10 isotopes are used in 90 % of all in vivo nuclear medicine procedures performed per year [2, 3].

-As an example, the radioisotope 99mTc is used in as many as 80 % of all diagnostic imaging studies of various organs all over the world.

-About 70,000 diagnostic images are taken each day, worldwide.

-It is used to locate tumors in the body, monitor cardiac function following heart attacks, map blood flow in the brain, and guide surgery. It is also used for brain, cerebral perfusion, myocardial, liver, spleen, bone and bone marrow, blood pool, hepatobiliary and pulmonary perfusion imaging [4, 5].

- 99mTc (T1/2 =6.01 h) that decays to 99gTc (T1/2 = 2.115x105 y) E γ =140.5 keV.- It can be bound into a variety of special molecules that target specific parts of the body when ingested or injected [6,7].

-It’s location within the body can then be pinpointed by detecting the-140.5 keV γ-ray in single photon emission computed tomography (SPECT) imaging.

-An alternative type of scan, called positron emission tomography (PET) can be done for diagnostic images by using positron emitter radioisotopes such as 11C(T1/2 =20.39 min) and 18F(T1/2 =109.77 min). These nuclides are short-lived

- 33P (T1/2 =25.34 d), beta emitter, Eβ = 248.5 keV Leukemia treatment, bone disease diagnosis/treatment (arteriosclerosis and restenosis) [8].

- 47Sc (T1/2 = 3.3492 d), Eγ = 159.4 keV – Alternative to 99mTc - 68Ga (T1/2 = 67.629 m), Eβ+ =1843.7(1.7%),1899.1(88.0%), 2921.1(8.94%) Positron emission tomography (PET), Alternative to 11C and 18F

CONVENTIONAL ROUTE OF PRODUCTION FOR THE PROPOSED MEDICAL ISOTOPES

-In conventional way some of the radioisotopes are produced by (n, γ), (n, p), (n, α) and (n, f) reactions of various isotopes using neutron flux in the reactor.

-Some of the other radioactive isotopes are produced in accelerator by different types of nuclear reactions using various charged particles.

-99mTc is produced in a generator from the parent 99Mo (T1/2= 65.94 h -About 90 % of the radioisotope 99Mo used in the world is produced in reactor from 235U(nth, f) reaction of high enriched (93 %) uranium(HEU) and 10 % from 98Mo(nth, γ) reaction.

-All the global supply of 99Mo is produced at just five reactors. About 85% of the 99Mo used in Europe and North America is produced at four reactors facilities: (a) in Europe, the high flux reactor (HFR) in Petten, Netherlands, (b) BR-2 in Mol, Belgium and (c) OSIRIS in Saclay, France and (d) in North America, the National Research Universal (NRU) Reactor in Chalk River, Ontario, Canada.-All these four reactors are over 40 years old [2].

33P is produced in the reactor from S(n, p) reaction in reactor using enriched 33S target.

- Isotopic composition of natural sulfur are 32S(95.02%), 33S(0.75 %), 34S(4.2 %) and 36S (0.02 %) respectively.

-In the natS(n, p) reaction, 32P having half-life of 14.26 days is always associated with 33P in the neutron irradiation of natural sulfur in a reactor.

-32P is a high energy beta emitter having end point energy of 1.71 MeV, whereas 33P is soft beta emitter having end point energy of 248.5 keV. -Trace contamination of 32P in the production of 33P poses limitation in its application. Besides this, production of 33P requires reactor or high flux neutron source

-Reactors or high flux neutron sources are always needs huge investment for their construction and maintenance and are located very far from the medical centers, where the clinical isotope is required.

ALTERNATIVE ROUTE FOR MEDICAL ISOTOPES

-Production of 99Mo-99mTc can be done from fast neutron induced fission of 238U using the fast reactor or accelerated driven sub-critical system (ADSs).-With fast neutrons, the 238U(n, f) reaction has low fission cross-section and is so far not used, whereas high neutron flux spallation source in ADSs is not yet developed.

-Activity of 99Mo-99mTc can be produced from 238U(p, f) and 100Mo(p, 2n) reactions [15-18]. These reactions have some threshold with low fission and reaction cross-sections even at high energy proton beam.

At high proton energy many other reaction channels such as (p, n), (p, α), (p, np) and (p, nα) open up resulting many reaction products from the 238U and 100Mo targets. To improve the production yield of 99Mo from 238U(p, f) and 100Mo(p, 2n) reactions, particle accelerators [14-18] should have high proton current.

-In 100Mo(p, 2n) reaction, the biggest disadvantage is that the final product 99mTc (T1/2= 6 h) is directly produced. Thus, its usefulness would be hampered if it needed to be shipped over great distance to the end users.

ALTERNATIVE ROUTES AND FACILITY TO BE USED FOR THE PROPOSED REACTIONS

(a) 100Mo(γ, n)99Mo and 238U(γ, f)99Mo-The gamma (bremsstrahlung) is obtained using electron accelerator available in EBC centre, Kharghar, Navi Mumbai.

(b) 32S(n,p)32P, 33S(n, p)33P, 47Ti(n, p)47Sc-The high energy neutrons are generated using D-D, D-T reactions at PURNIMA facility at BARC, Mumbai and 7Li(p,n) reactions using proton beam at FOTIA ,BARC and BARC-TIFR Pelletron facilities.

(c) 68Zn(p, n)68Ga-The charged particle like proton beam is available in Pelletron facility at TIFR, and FOTIA facility at BARC, Mumbai and VECC, Kolkota.

(A) PHOTON (BREMSSTRAHLUNG) INDUCED REACTION (100Mo(γ,n)99Mo ) AND FISSION (238U(γ,f))99Mo Using 10 MEV ELECTRON LINAC OF EBC CENTER AT KHARGHAR, NAVI-MUMBAI. INDIA.

- Bremsstrahlung is the electromagnetic radiation emitted by electrons when they pass through matter (Coulomb field).

- Synchrotron radiation is an analog to bremsstrahlung, differing in that the force which accelerates the electron is a macroscopic (large-scale) magnetic field.

PHOTON (BREMSSTRAHLUNG) SOURCE a. Mono-energetic photon from (i) Annihilation gamma using positron beam (ii) Laser beamb. Bremsstrahlung spectrum from electron linac

0 2 4 6 8 10 12

1000

10000

100000

1000000

ph

oto

n f

lux (

Arb

ita

ry u

nit)

Photon Energy (MeV)

10 MeV bremsstrahlung

. Bremsstrahlung spectrum from 10 MeV electron beam obtained using EGS4 computer code [9].

0 10 20 30 40 50 60 70 801E-5

1E-4

1E-3

0.01

0.1

Bre

msstr

ahlu

ng F

lux-a

rb. uin

t

Photon Energy-MeV

Electron Beam Energy 12 MeV 14 MeV 16 MeV 45 MeV 50 MeV 55 MeV 60 MeV 70 MeV

Fig. Plot of Photon flux in arbitrary unit as a function of photon energy calculated using GEANT4 code

PRODUCTION OF PHOTON (BREMSSTRAHLUNG) AND IRRADIATION OF SAMPLES

-Thermo ionic source Lithium hexaborate-Beam specification -Microtron or Microtron EBC Electron linac (KOREA)Electron linac 8 MeV 10 MeV 100 MeV 3.0 GeV energy range 8 MeV 10-12 MeV 50-70MeV 3.0 GeV Beam current 50 mA 100-200 mA 100 (10-50) mA 100-200 mA Pulse width 2.5 µs 10 μs 1-2 (1.5) μs 1 ns Repetition rate 250 Hz 300-400 Hz 10-12 (3.75) Hz 10 Hz

Electron beam

Ta, W target (0.1-1mm)

SampleELBE (Germany) SAPHIR (France)20 MeV 35 MeV12-16 MeV 11.5-17.3 MeV ----- 100 mA 10 ps 2.5 μs 13 MHz 25Hz

Beam specification

Microtron (Magalore)INDIA

Electron linacEBC (Kharghar)INDIA

Electron linacELBE(Dresden)GERMANY

Electron linacSAPHIR (CEA)FRANCE

Beam Energy

8 MeV 10 MeV 12-16 MeV 11.5-17.3 MeV

Peak Beam Current

50 mA

100-200 mA

--- 100 mA

Pulse width 2.5 µs 10 µs 10 ps 2.5 µs

Pulse repetition rate

250 Hz

300-400 Hz

13 MHz 25 Hz

Average Beam Current

0.3 mA

0.3-0.8 mA

555 µA

6.25 µA

The beam specification of the electron accelerators are given below.

Schematic diagram showing the arrangement used for bremsstrahlung irradiation.

Converter – High density material like Nb, Mo, Ta, W, Th, U, High-Z material is better

Fig: Schematic diagram showing the arrangement for the production of bremsstrahlung

EXPERIMET FOR (γ, n) REACTION CROSS-SECTION OF 100MOUSING ELECTRON LINAC AT KHARGHAR, NAVI-MUMBAI, INDIA

-The radionuclide 99Mo (T1/2 = 65.94 h) was prepared from two types of reactions: 238U(γ, f) and 100Mo(γ, n) reactions.

-The bremsstrahlung radiation was generated by impinging an electron beam on a tantalum metal foil situated in front of the scanning electron beam . The thickness of Ta target was 0.25-0.5 mm with a size of 1 cm x 1 cm. It was placed on a suitable stand at a distance 20 cm from the beam exit window.

-Metal foils of natU (0.6587-1.2414 g with area 2-3.6 cm2), natMo (0.1191-0.3931 g with area 1.96 cm2) and 197Au (0.05435-0.1297 g with area 2.5 cm2) were wrapped separately with 0.025 mm thick super pure Al foil.

-The Al wrapper acts as a catcher of the fission or reaction products recoiling out from the photo-fission of U, photo-nuclear reaction of Mo and Au metal foils during the irradiation. The target of natU, natMo and 197Au wrapped with additional Al foil was placed below the Ta foil for irradiation.

-The 197Au(γ,n)196Au foil was used to determine the bremsstrahlung flux.

-The target assembly was irradiated for 3-4 h with the bremsstrahlung radiation produced by bombarding the 10 MeV electron beam on Ta metal foil.

-During the irradiation, the peak current of the electron beam during irradiation was 100 mA, at a frequency of 400 Hz and a pulse width of 10 μs. Thus the average continuous current was only 0.4 mA, resulting from beam power of 4 kW at electron energy of 10 MeV.

-After the irradiation, the irradiated targets were cooled for 0.5-1.5 h. Then the irradiated targets natU, natMo and 197Au along with Al catcher were mounted separately on three different Perspex plates.

-The γ-ray counting of the fission and reaction products in the irradiated natU, natMo and 197Au was done by using an energy- and efficiency-calibrated 80 cc HPGe detector coupled to a PC based 4K-channel analyzer in live time mode.

-The energy and efficiency calibration of the detector system was done by counting the γ-ray energies of standard 152Eu source keeping the same geometry, where the summation error was negligible.

EXPERIMENTAL DETAILS FOR 238U(γ,f) reaction at SAPHIR (FRANCE) AND and 100Mo(γ,n) at ELBE (GERMANY)

# End-point bremsstrahlung energy of 11.5-17.3 MeV from 35 MeV electron LINAC (SAPHIR) at CEA, Saclay, France.$- Bremsstrahlung was produced by impinging pulsed electron beam on a water cooled tungsten of size (d=5 cm X t=5 mm).$- 5.6 g of natU metal rod (d=2.74 mm X l=5 mm) was mounted inside a pneumatic rabbit holder. It carry the sample from the site to irradiation room. $- Irradiated for 30 minutes brought back pneumatically within few seconds near the detector.

# End-point bremsstrahlung enrgy of 12-16 MeV from 20 MeV electron linac (ELBE) at Helmholtz-Zentrum Dresden-Rossendorf (HZDR) Dresden, Germany.$-Bremsstrahlung was generated by impinging the electron beam on a solid graphite beam dump (site for irradiation (flux ~109 to 1010 photons cm-2 s-1)$- 54.8-80.4 mg of natMO metal of 1 cmX0.6 cm size+ 83.2-101.6 mg of Au metal of 0.48 cm2 size was loaded on a sample holder and sent one at a time to the place of irradiation using pneumatic carrier facility. Irradiation for 8.5 -10.5 hours.

$- The γ-rays activities of the fission products were measured by ORTEC 40-90 % HPGe detector coupled to a PC based 8-16K channel analyzer. $-Resolution of detector systems were 2.0 keV FWHM at 332.0 keV γ-line of 60Co.

ANALYSIS OF REACTION PRODUCTS *Off-line gamma ray spectrometric technique of reaction products by using HPGe detector coupled to a PC based 4K- channel analyzer.

1 2 3 4

6

5

For gamma ray spectrometric technique1: High-Purity Coaxial Germanium detector (HPGe), (ORTEC, Model GEM-20180-p, Serial No. 39-TP21360A); 2: Preamplifier (ORTEC, Model 257 P, Serial No. 501); 3: Amplifier (ORTEC-572);4: 4-Input Multichannel Buffer, Spectrum Master-919, (ORTEC );5: Computer (Maestro, GammaVision) 6: Bias supply (High Voltage: +2000 v) ( ORTEC - 659)

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355.7

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Co

un

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Channel No.

17.6 h cooled spectrum

Fig: Typical γ-ray spectrum of an irradiated Au foil showing the γ-lines of 196Au.

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un

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Channel No.

16 hours cooled spectrum

Fig: Typical γ-ray spectrum of an irradiated natMo showing the γ-lines of 99Mo.

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24 h cooled spectrum

Fig: Gamma ray spectrum of fission products from 238U(γ, f) reaction, EBC, Kharghar, INDIA.

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2127.6

keV

(98 N

bm)

2639.6

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(138 C

sg )

2543.8

keV

(93 S

r)

2196 k

eV

(89 R

b)

2218 k

eV

(138 C

sg )

2416.2

keV

(133 S

b)

2004.8

keV

(138 X

e)

2032.1

keV

(101 M

o)

2393.1

keV

(88 K

r)

2570.1

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(89 R

b)

2176 k

eV

(95 Y

)

2015.8

keV

(138 X

e) irradiation time =30 min

cooling time = 32 mincounting time=3600 sec

Energy (keV)

1854.4

keV

(131 S

b)

1612.4

keV

(104 T

c)

Counts

Counts

1678 k

eV

(135 I)

1009.8

keV

(138 C

sg )1024.3

keV

(91 S

r)

1836 k

eV

(88 R

b)

1768.3

keV

(138 X

e)

1529.8

keV

(88 K

r)

1260.4

keV

(135 I)

1131.5

keV

(135 I)

1524.7

keV

(146 P

r)

1435.8

keV

(138 C

sg )

1383.9

keV

(92 S

r)

1248.3

keV

(89 R

b)

1078.7

keV

(142 B

a)

1032.1

keV

(89 R

b)

Counts

113+114+117 k

eV(237 U

-K)

96+101 k

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(237 U

-K)

749.8

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(91 S

r)

667.7

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(132 Im

,g) )

793.5

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bg )

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b)

566 k

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(134 T

e)

529.9

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(133 I)

151.1

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(85 K

rm)

165.9

keV

(139 B

a)

943.4

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(131 S

b)

918.7

keV

(94 Y

)

884.1

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(134 Ig )

847 k

eV

(134 Ig )

767.2

keV

(134 T

e)

743.4

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(97 Z

r)723.9

keV

(145 C

e)

642.3

keV

(142 L

a)

590.9

keV

(101 M

o)

511 k

eV

462.8

keV

(138 X

e)

453.9

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(146 P

r)

434.5

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(138 X

e)

402.6

keV

(87 K

r)

358 k

eV

(104 T

c)

304.7

keV

(141 B

a)

277 k

eV

(141 B

a)

258.4

keV

(138 X

e)

210 k

eV

(134 T

e)

190.3

keV

(141 B

a)

Fig. γ- ray spectrum of fission products in the 17.3 MeV bremsstrahlung induced fission of 238U at SAPHIR, Saclay, France.

CALCULATIONS AND RESULTS(A)Calculation of 99Mo activity from the experimentally obtained

photo-peak activity

-The photo-peak activities (Ai) of the gamma lines of 99Mo and 196Au from the 238U (γ, f), 100Mo((γ, n) and 197Au (γ, n) reactions were obtained using decay equation

Ai = N<σ>ΦYaε [1- exp(-λt) exp(-λT) (1- exp(-CLλ)/λ] (1)

N = Number of target atoms, <σ> = fission/reaction cross section, Φ = photon flux, a = gamma ray abundance, ε = efficiency of the detector t = irradiation time, T = Cooling time, CL = Counting timeY = Cu. Y. of 99Mo (= 5.718±0.883 % for 238U(γ10 MeV, f) reaction)

-The efficiency (ε) of the γ-ray energy for the detector system at a fixed geometry was calculated as: ln ε = Σ Cn (ln E)n (2)

where Cn represents the fitting parameters and E is the γ-ray energy for a 152Eu standard source with γ-ray energies from 121.8 keV to1408.0 keV.

-The ‘ε’ value from Eq. (2) and ‘a’ from refs [10, 11] are related to the disintegration per second (DPS) of 99Mo with the following relation

DPS = Aobs(CL/LT) eλT / [(LT) (ε) (a)] (3)

NUCLEAR SPECTROSCOPIC DATA USED IN THE CALCULATION --------------------------------------------------------------------------------------------------- Reaction Nuclide Half-life Threshold γ- ray energy in Type (MeV) keV (abundance) --------------------------------------------------------------------------------------------------- 100Mo(γ, n) 99Mo 65.94 h 8.29 140.5(89.43), 739.5(12.13) 197Au((γ, n) 196Au 6.183 d 8.07 322.98(22.9), 355.69(87), 426.0(7)----------------------------------------------------------------------------------------------------

(B) Calculation of 99Mo activity using the photon flux and photo -fission (reaction) cross-section

-The initial activity (Ai) of 99Mo in natU(γ, f) and natMo(γ, n) reactions per gram of the sample for Eγ = 10 MeV was calculated for 24 h of irradiation and using experimentally determined photon flux(Φ).

- The initial activity (Ai) of 99Mo is given as Ai = NσΦY (1 – e-λt) (4)

-The Φ term was calculated from the photo-peak activity and reaction cross-section of the monitor 197Au((γ, n).

λ Ai

Φ = ------------------------------------------------------------------- (5) N<σ>RYaε [1- exp(-λt) exp(-λT) (1- exp(-CLλ)] <σF> = Σ(σF Φ)/ΣΦ and <σR> = Σ(σR Φ)/ΣΦ (6)

80 90 100 110 120 130 140 150 160

0

2

4

6

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SIO

N Y

IELD

S (

%)

MASS NUMBER

238U(n,f)

80 90 100 110 120 130 140 150 160

0

2

4

6

8

10

12

238U(,f)

Fig: Fission yield vs. their mass number in the 238U(γ, f) and 238U(n, f) reactions.

5 10 15 20 25 30 35 400

50

100

150

200 fi

ss (

mb)

E (MeV)

Refs.[30-37] Talys1.6 Talys1.6-default

Plot of 238U(γ, f) reaction cross-section from TALYS 1.6 code andexperimental data.

Plot of 100Mo(γ, n) reaction cross-section from TALYS 1.6 code and experimental data.

8 10 12 14 16 18 20 22

0

100

200

300

400

500

600

(m

b)

E(MeV)

Varlamov et al -2010 TALYS 1.6

Fig: Plot of experimental and theoretical 197Au (γ, n)196Au reaction cross-section as a function of photon energy.

RESULTS AND DISCUSSION

Table 1. Experimentally obtained 99Mo (T1/2=65.94 h) quantities produced for one gram of the samples of one square cm size in for 24 hours of irradiation with scanning electron beam of 10 Hz at 10 MeV with 4 kW beam power from natU(γ, f) and natMo(γ, n) reactions.----------------------------------------------------------------------------------------------------------- Reaction γ-ray γ-ray Activity of 99Mo (μCi) product energy abundance Experimental Calculated value* based on (keV) (%) expt –σ (TALYS –σ) -----------------------------------------------------------------------------------------------------------natU(γ, f)99Mo 140.5 89.43 0.324±0.036 739.8 12.13 0.293±0.035 ---------------- 0.309±0.050 0.313±0.049 (0.452±0.094) natMo(γ, n)99Mo 140.5 89.43 0.311±0.046 739.8 12.13 0.326±0.015 ----------------- 0.318±0.048 0.389±0.014 (0.412±0.015)-----------------------------------------------------------------------------------------------------------

Experimental work carried out at

End-point Bremsstrahlung energy (MeV)

Activity of 99Mo (μCi) in natU(γ,f) reaction per g for 24 h irradiation

Activity of 99Mo (μCi) in natMo(γ,n) reactionper g for 24 h irradia

Microtron (Mangalore,India)

8.0 0.0255±0.0013 --

EBC (Kharghar, India)

10.0 0.309±0.050 0.318±0.048

SAPHIR (CEA, France)

11.5 0.369±0.013 --

ELBE (Dresden,Germany)

12.0 -- 0.183±0.001

SAPHIR (CEA, France)

13.4 0.452±0.021 --

ELBE (Dresden,Germany)

14.0 -- 0.823±0.073

SAPHIR (CEA, France)

15.0 0.545±0.027 --

ELBE (Dresden,Germany)

16.0 -- 4.292±0.288

SAPHIR (CEA, France)

17.3 0.735±0.011 --

Table 2. The amount of the 99Mo produced per gram of the natMo and natU samples at different end-point bremsstrahlung energies are shown below.

*The cumulative yields of 99Mo from natU(γ, f) reaction used as (5.718±0.883)% is based on refs [12, 13].

-The experimental flux was (8.004±0.288) x109 photon cm-2s-1 is based on the experimental flux-weighted 197Au(γ, n)196Au reaction cross-section of 38.65 mb from ref. [14].

-The photon flux of (5.624±0.208) x109 photon cm-2s-1 is based on the flux-weighted 197Au(γ, n)196Au reaction cross-section of 55 mb from TALYS[15].

-The experimental and TALYS cross-sections for natU(γ, f) reaction are 6.75 and 13.87 mb respectively.

-The experimental and TALYS cross-sections for natMo(γ, n) reaction are 17.03 and 25.67 mb respectively.

-The flux ratio of 238U (γ,f) reaction from 4 to 10 MeV to that of 197Au (γ,n) reaction from 8.07 to 10 MeV bremsstrahlung radiation is 6.693.

-The flux ratio of 100Mo (γ,n) reaction from 8.29 to 10 MeV to that of 197Au (γ,n) reaction from 8.07 to 10 MeV bremsstrahlung radiation is 0.785

Table 3. Comparison of 99Mo activity calculated from natU(γ,f), natMo(γ,n), natU(n1.9 MeV,f), natMo(nth, γ) and 235U(nth, f) reactions for 24 h irradiation of one gram sample with total flux (Φ) of 1.0x1013 photon (neutron) cm-2 s-1. The photon flux is produced from the focused electron beam without scanning the position of the electron beam in the exit window of the accelerator.-------------------------------------------------------------------------------------------------------------------Reaction Incident Cumulative Ratio of Φ <σ>(mb) Activity ofType Energy Yields of 99Mo >4(8.29) MeV in MeV 99Mo (μCi) in % to total Expt. (TALYS) -------------------------------------------------------------------------------------------------------------------natU(γ, f) 10 MeV 5.72 0.09949 6.75 (13.87) 5.8 (11.9) 11 MeV 6.76 0.11354 10.79 (19.03) 12.5 (22.1) 15 MeV 6.13 0.15681 26.98 (42.47) 39.3 (61.9) 20 MeV 6.17 0.19663 40.48 (50.86) 74.4 (93.5) 25 MeV 6.48 0.22473 41.75 (51.08) 85.0 (104.0)natU(n, f) 1.9 MeV 6.28 0.01 500 - 47.9 -natMo(γ, n) 10 MeV - (0.0117) 17.03 (25.67) 7.2 (10.9) 11 MeV - (0.0206) 20.51 (30.88) 15.3 (23.1) 15 MeV - (0.0535) 51.06 (59.53) 99.2 (115.7) 20 MeV - (0.0876) 59.11 (59.74) 188.1 (190.1) 25 MeV - (0.1192) 50.52 (55.27) 218.7 (239.3)natMo(n, γ) 0.025 eV - - 130 - 12000 -235U(n, f) 0.025 eV 6.18 - 584000 - 5.57x106 -------------------------------------------------------------------------------------------------------------------

From Table 3, the activity of 99Mo per day per gram is 220-240 μCiusing 1 mA peak electron current (4 μA average current) electron linac with400 Hz repetition rate with 10 μs pulse width and only area of one cmsquare sample size with focused beam. This gives the electron flux of 2.5x1013 electrons per second. With 40% photon conversion factors results aphoton flux of 1.0x 1013 photons per second. However, the 1 mA peak current at 25 MeV beam energy correspond to 100 watts of beam power.Therefore for 10 kW machine the peak current should be taken as 100 mA.Thus the 99Mo production can be increased by increasing the different parameters of Table 2 by following factors:

(i) 10 factor for enrichment i.e. from 9.6% of 100Mo in natMo to 100% in enriched 100Mo(ii) 10 factor for 10 gram sample instead of one gram(iii) 100 factor for 100 electron linac instead of one electron linac(iv) 100 factor for 10 kW electron linac instead of 100 watts Thus the activity of 99Mo per day = 220 μCi x10 x10 x100 x100 = 220 Ci.

Therefore the sandwich targets of pure 100Mo with focused beam can produce 480 Ci of 99Mo per day, which is the demand of DOE.

From Table 1 the activity of 99Mo per day per gram is around 0.32 μCi using 4 kW electron linac with 400 Hz repetition rate with 10 μs pulse width and only area of 1 cm square sample size. Scanning beam is 10 Hz, covering twice an area of 500 squares cm per one oscillation (back and forth). The sample activity of 0.32 μCi is for the sample irradiation utilizing fraction of the area (1/500) and beam power. In100 electron linacs of 25 MeV energy with 10 kW power for 10 grams enriched samples with 500 square cm area the activity of 99Mo production can be increase by following factor of times(i) 2.5 factor for 10 kW electron linac instead of 4 kW(ii) 10 factor for enrichment i.e. from 9.6% of 100Mo in natMo to 100% in enriched 100Mo(iii) 10 factor for 10 gram sample instead of one gram(iv) 30 factors for cross-section at 25 MeV compared to 10 MeV, which is discussed in Table 2.(v) 100 factor for 100 electron linac instead of one electron linac(vi) 500 factor for 500 square cm area instead of one square cm

Thus the activity of 99Mo per day= 0.32 μCi x10 x10 x30x100 x500= 120 CiTherefore a sandwich method with scanning beam can produced 240 Ci of 99Mo per day. It may require about 210 linacs instead of 100 linacs to produce required activity of 500 Ci per day as required by DOE.

RADIOCHEMICAL SEPARATION OF 99mTc from 99Mo

*516.9 mg of MoO3 was irradiated for 4 hours with end point bremsstrahlung energy of 10 MeV with peak current of 33 mA

*MoO3 was dissolved with 5 ml of 0.5N NaOH and estimated by off-line γ-ray spectrometric technique.

*Then 99mTc was extracted with MIBK and estimated by same off-line γ-ray spectrometric technique.

*Chemical yield of the 99mTc in first extraction itself was 70% and it is free from 99Mo

*Irradiation of 238U and separation of 99Mo- 99mTc is yet to be done

0 250 500 750 1000-250000

0

250000

500000

750000

1000000

1250000

1500000

1750000

2000000

C

OU

NTS

ENERGY (keV)

Separated 99Tc from 99MoCounting time=1200 sec

140 keV (99mTc)

Fig. Radio-chemically separated 99Tc from irradiated MoO3 with end-point bremsstrahlung energy of 10 MeV.

Conclusions(i) The medical isotope 99Mo was experimentally produced from the natU(γ,f) and natMo(γ,n) reactions for end-point bremsstrahlung energy of 10 MeV obtained from scanning electron beam. This is better than the focused electron beam from the point of view of cooling the target and thus is important for its practical application.

(ii) The activity of 99Mo produced from the natU(γ,f) reaction for end-point bremsstrahlung energy of 10 MeV was found to be slightly lower than from the natMo(γ,n) reaction. The activity of 99Mo from the natU(γ,f) and natMo(γ,n) reactions are estimated using photon flux and experimental and TALYS flux-weighted cross-sections for natU(γ,f) and natMo(γ,n) reactions. The estimated activity of 99Mo from the natU(γ,f) and natMo(γ,n) reactions shows an general agreement with the experimental value.

III) 99Tc was radio-chemically separated from the irradiated MoO3. The chemical yield in the first extraction is 70%. (iv) The natMo(γ,n) and natU(γ,f) reactions provide an alternative route to 98Mo(n,γ) and 235,238U(n,f) reactions circumventing the need for a reactor. It is possible to produced the 99Mo-99mTc by the photo-reaction of natMo or 100Mo and photo-fission of natU to fulfill the requirement of DOE.

The flux-weighted average (γ,xn) reaction cross-sections of natZn induced with bremsstrahlung end-point energies of 50, 55, 60 and 65 MeV have been determined by using the off-line γ-ray spectrometric technique at Pohang Accelerator Laboratory (PAL), South Korea. The theoretical photon-induced reaction cross sections of natZn as a function of photon energy were taken from TENDL-2013 nuclear data library based on TALYS 1.6 program. For comparison with our experimental results, the flux-weighted average cross-sections for the existing experimental data with the mono-energetic photons and the theoretical values from TENDL-2013 were obtained. The reaction cross-section values measured at different end-point bremsstrahlung energies from the present work and from literature are found to be in good agreement with the theoretical values. It was found that the individual natZn(γ,xn) reaction cross-sections increase sharply from reaction threshold energy to certain values where the next reaction channel opens. There after it remains constant for a while, where the next reaction channel increases. Then it decrease slowly with increase of end-point bremsstrahlung energy due to opening of different reaction channels.

natZn(γ,xn) reaction cross-sections measurement in the bremsstrahlung end-point energies of 50, 55, 60 and 65 MeV

EXPERIMENTAL DETAILS FOR 68Zn(γ,x) reaction at PAL (Korea)

# End-point bremsstrahlung energy of 50-65 MeV from 100-MeV electron LINAC $- Bremsstrahlung was produced by impinging pulsed electron beam on 0.1 mm W tungsten of size (d=5 cm X t=5 mm).•The Zn sample was positioned at 12 cm from W target and zero degree about the electron beam direction

ExperimentNo.

Electron BeamIrradiationTime (min)

ZnMass (g)

AluminumMass (g)Energy (MeV)

Current (mA)

1 50 12.0 20.0 0.2116 0.055

2 55 20.0 20.0 0.194 0.049

3 60 16.0 30.0 0.185 0.061

4 65 16.0 30.0 0.199 0.026

Experimental conditions and characteristics of samples

Typical gamma spectrum

PREPARATION OF MEDICAL ISOTOPES USING NEUTRONSOURCE for 33P - 33S(n, p)33P and 32S(n, p)32P reaction

NEUTRON SOURCES (Few examples) & NEUTRON SPECTRUM a. neutron induced fission of actinides - in reactor APSARA – neutron flux = 1.2x 1012 n s-1 cm-2

CIRUS – neutron flux = 5.0x 1012 n s-1 cm-2

DHRUVA – neutron flux = 1.0x 1013 n s-1 cm-2

b. spontaneous fission of actinides e.g. 252Cf (T1/2 = 2.65 y) – neutron flux = 2.30x 1012 n s-1 g-1

MEDIUM ENERGY NEUTRON INDUCED FISSION OF ACTINIDES

NEUTRON SOURCES

c. 9Be(α,n) – α source – 210Po, 226Ra, 227Ac, 238,239Pu, 241Am, 242,244Cm, e.g. 241Am/Be (T1/2= 433 y), Eα= 5.48 MeV, 70 neutrons per 106 α particle 15-23 % neutron yield with En <1.5 MeV

d. photo neutron induced fission and reactions reaction Q-value (MeV) Actinides ((γ,f) -3.6 to -6.7 9Be(γ,n) -1.666 2H(γ,n) -2.226 γ from 24Na, 28Al, 38Cl, 56Mn, 72Ga, 76As, 88Y, 116mIn,124Sb, 140La, 144Pr from electron LINAC or MICROTRON

e. Accelerator based neutron sources e.g. 2H(2H, n), 3H(2H, n), 7L(p, n) or 9Be(d, n) reactions, which was done at PURNIMA, PUNE AND TIFR reaction Q-value (MeV) neutron energy neutron per 1 mA of D 2H(2H,n) +3.26 2.45 MeV 109 n/s from D 3H(2H,n) +17.6 14.8 MeV 1011 n/s from T

7Li(p, n)7Be -1.644 (+1.881) Ep-1.881 MeV 105 – 108 n/s

DIFFERENT 7Li(p, n) REACTIONS FOR NEUTRON FLUX GENERATION

No. Reactions Q-Value (MeV) Threshold energy MeV) 1. 6Li(p, n)6Be −5.07 5.92 2. 6Li(p, np)5Be −5.67 6.62 3. 7Li(p, n)7Be −1.644 1.881 (Ground-state transition) 4. 7Li(p, n)7Be∗ −2.079 2.38 (First excited-state transition) 5. 7Li(p, n3He)4He −3.23 3.6 (Three-body break up reaction• 7Li(p, n)7Be ∗∗ -6.18 7.06 (Second Excited transition)

#Primary neutron Energy peak at (Ep – 1.881) MeV

0 1 2 3 4 50.00

0.05

0.10

0.15

0.20

0.25neu

tron s

pec

trum

(ar

bit

ary u

nit

)

En(MeV)

Ep=5.6 MeV

Fig. Neutron spectrum for 7Li(p, n)7Be reaction at EP = 5.6 MeV calculated using

TALYS 1.6.

Fig. Neutron spectrum for 7Li(p, n)7Be reaction at EP = 18 MeV

calculated using the results of Poppe et al. (1976).

EXPERIMENTAL PROCEDURE FOR NEUTRON INDUCED RECTIONS

-For 33S(n, p)33P and 32S(n, p)32P reaction

(i) TARGET PREPARATION - Metal target of natS and flux monitor (Au, In) were separately wrapped with 0.025 mm thick Al.

(Iii) IRRADIATION - For 33S(n, p)33P and 32S(n, p)32P reaction cross-section irradiation were carried out at En=0.025 eV using thermal column of the reactor APSARA at BARC, Mumbai with neutron flux of1.105x108 n cm-2 s-1

- For selective preparation of 33P from natS(n,p) reaction irradiation were carried out at En <1.2 MeV from 7Li(p, n) reaction with Ep= 3 MeV using FOTIA, BARC or BARC-TIFR Pelletron facility, Mumbai, India.

(iii) BETA COUNTING -The beta counting of the 33P and 32P were carried out using scintillator counting in RCD, BARC

33S(n, p)33P and 32S(n, p)32P reaction cross-section

Proton beam

Li foil

Thick Ta foil (beam stopper)

Neutrons

Flange

(S), In

2 cmThin tantalum wrapping foil

Fig.1. IRRADIATION OF SAMPLES AND MONITOR WITH THE NEUTRONS FROM 7Li(p, n) REACTION

Fig. beta spectrum of the irradiated sulfur

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