Production of and research on medical radioisotopes

at the Heavy Ion Laboratory, University of WarsawJ. Jastrzębski*1, J. Choiński1, A. Jakubowski1, M. Sitarz1,2, A. Stolarz1, K. Szkliniarz3, A. Trzcińska1, W. Zipper3

1 Heavy Ion Laboratory, University of Warsaw, Pasteura 5a, 02-093 Warszawa, Poland 2 Faculty of Physics, University of Warsaw, Pasteura 5, 02-093 Warszawa, Poland

3 Institute of Physics, University of Silesia, Uniwersytecka 4, 40-007 Katowice, Poland* Correspondence to: jastj@slcj.uw.edu.pl

Irradiations & measurementsThere are two cyclotrons at the Heavy Ion Laboratory used for the production of research quantities of medical radioisotopes:

211At

U-200P2 - 10 AMeV4He - 40Armax. 1 µAinternal beam

PETtrace16 AMeV

p - d0.5 - 4 µA

external beam

Targets used at U-200P are prepared as pellets bundled in thin aluminium foil (Sc and Se/As production) or by direct melting into backing (At production). PETtrace targets are material pressed using a hydraulic press. Each target consists of additional Cu foil (beam intensity monitor). The selected target and additional Al foil (energy degrader) thicknesses reflect desired reactions cross-sections range in the target material.After the irradiation, targets are left inside the cyclotron for about one hour before their activity measurements with HPGe detectors placed inside the Pb shielding are done. The aim is to determine the activity at the End Of Bombardment (AEOB) of each isotope produced during an irradiation and the yield of its production [MBq/µAh]. Results are compared with theoretical (thick) target yield (TTY) values:

σ - reaction cross sectionZ - projectile atomic numberS - projectile stopping powerNA - Avogadro’s numberH - isotopic enrichment of the target material

TTY=HNA λZ eM ∫

Emin

Emax σ (E)S(E)

dE

43Sc & 44mSc/44Sc

α range in tissue = 55-77 µmcell size ≈ 10 µm

α LET ≈ 100 keV/µmhigh probability of the double-strand DNA breaking

Summary

The cyclotrons operating at the Heavy Ion Laboratory of the University of Warsaw have been extensively employed in recent years for the production of medical radioisotopes: 99mTc, 72Se/72As, 211At, 43Sc and 44mSc/44Sc using α, p and d beams. The intensity of α beam is sufficient for the production of research quantities of the studied radioisotopes, but yet a more intense beam would be needed for their production for clinical applications. An upgrade of the U-200P cyclotron is in preparatory phase.

E - projectile energyM - atomic mass of targetλ - product decay constante - electron charge

43Sc

0

0

373

43Ca

22%

78%

7/2-

5/2-

7/2-

3.9 h

99mTcA cyclotron production route of this popular, 6 h SPECT radioisotope is being inves-tigated at HIL (in collaboration with National Centre for Nuclear Research and Insti-tute of Nuclear Chemistry and Technology) within IAEA international programme.

Qaim et al., 2014. Evaluation of excitation functions of 100Mo(p,d+pn)99Mo and 100Mo(p,2n)99mTc reactions: Estimation of long-lived Tc-impurity and its implication on the specific activity of cyclotron-produced 99mTc. Appl. Radiat. Isot. 85, 101–113

72Se/72As

72Se

0

46 100%

0+

1+

8.5 d

72As

0

0

834

72Ge

68%

17%

15%

2-

2+

0+

26 h

α energy [MeV]

30

72Se0.19(3)

72As2.7(1)

TTY [MBq/µAh]

α energy[MeV]

293031

211At37(6)46(5)55(7)

210At0.009(2)0.06(1)0.5(1)

TTY [MBq/µAh]

α + natCaCO3

& natCa metal43Sc production

yield

α + natCaCO3 (20 – 0 MeV)4 h irradiation

43Sc, 44Sc = instead of 18F, 68Ga44Sc = three photon PET

44mSc/44Sc = in vivo generator

0

207Bi

9/2-33 y

0

211At

9/2-7.2 h

0

67.9

207Pb

13/2+

1/2-

100%

16%

84%

42%α5.9 MeV

0

211Po

9/2+0.5 s

0.8 s

58%

100%α7.5 MeV

One should avoid the formation of the dangerous 210At by the (α,3n) reaction. TTY of 211At and 210At for 209Bi target and different bombarding energies are shown below:

The 211At is one of the most promising α emitters for Targeted Alpha Therapy. Its production has been investigated using 209Bi target (~98 mg/cm2) by the (α,2n) reaction. For 29 MeV α, TTY = 37 MBq/μAh. Therefore with 25 μA and 7 h irradiation, 4.7 GBq activity of 211At at EOB can be produced.

α + 209Bi211At production yield

α + 42CaCO3 (68%)44Sc & 44mSc

production yield

α + 42CaCO3 68%(29 - 12 MeV)12 h irradiation

TTY[MBq/µAh]

84(4)44(7)4.7(8)

isotope43Sc44Sc

44mSc

targetnatCaCO342CaCO342CaCO3

α energy[MeV]

202929

The production of 43Sc was investigated via the 40Ca(α,p) using natCaCO3

and natCa metal targets (96.9% 40Ca in natCa). The observed impurities level in the natCaCO3 (<0.05% of 43Sc AEOB) makes this production route extreme-ly attractive. The use of enriched 40CaCO3

(99.99% 40Ca) yields impurities lower than 10-5% for over 15 h after the EOB. Also, irradiating the natCa metal with the α-beam of 25 µA (from commercially availa-ble cyclotron), a 14 GBq of 43Sc at EOBcould by produced after a 4 h irradiation.

11% while for 15 MeV proton is 0.5% and 15 MeV deuterons is 2.2%.

Valdovinos et al., 2015. Separation of cyclotron-produced 44Sc from a natural calcium target using adipentylpentylphosphonate functionalized extraction resin. Appl. Radiat. Isot. 95, 23

proton energy [MeV]16-826-8

6 h irradiation, 40 µA:Long-lived impurities

<0.02% EOB<0.03% EOB

AEOB 99mTc

[GBq]64

150

99mTc372(45)865(65)

99Mo2.4(6)31(5)

TTY [MBq/µAh]

72As via the 70Ge(α,pn) reactions. With ir-radiation time 8 h and beam intensity 25 μA a 38 MBq AEOB of 72Se/72As generator could be produced. Assuming 100% chemical extraction effciency, 3 days after the EOB a 31 MBq and 15

α + natGeO272Se & 72As

production yield

A natGeO2 target was irradiated with a 30 MeV α-beam to produce 72Se via the 70Ge(α,2n) and

long physiologicalprocesses investigations

potential for PET where no cyclotron is available

72Se/72As = long-lived generator

p + 100Mo 99.815% (26 – 8 MeV)

days after EOBa 13 MBq of 72As can be extracted.

To get 44Sc and 44mSc via the (α,pn) and (α,np) the enriched 42CaCO3 (68% 42Ca) target was used. The results above were extrapolated for commercially available 95.9% enrichment. The production efficiency of 44Sc for α is smaller than for proton or deuteron induced reactions. However, for 29 MeV α, the 44mSc/44Sc TTY ratio is

Severin et al., 2012. Cyclotron Produced 44gSc from Natural Calcium. Appl. Radiat. Isot. 70, 1526

6 h irradiationp + 100Mo (99.815%)99mTc production yield

Our work is focused on the determination of the impurities in the irradiated samples as a function of the proton bombarding energy and the target enrichment. Yields of long lived Tc isotopes, impossible to eliminate by chemistry, were calculated with EMPIRE evaporation code.

Duchemin et al., 2015. Production of scandium-44m and scandium-44g with deuterons on calcium-44: cross section measurements and production yield calculations. Phys. Med. Biol. 60, 6847