Production of and research on medical radioisotopes at the ... · Production of and research on...
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Production of and research on medical radioisotopes at the Heavy Ion Laboratory, University of Warsaw J. Jastrzębski* 1 , J. Choiński 1 , A. Jakubowski 1 , M. Sitarz 1,2 , A. Stolarz 1 , K. Szkliniarz 3 , A. Trzcińska 1 , W. Zipper 3 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: [email protected] Irradiations & measurements There are two cyclotrons at the Heavy Ion Laboratory used for the production of research quantities of medical radioisotopes: 211 At U-200P 2 - 10 AMeV 4 He - 40 Ar max. 1 µA internal beam PETtrace 16 AMeV p - d 0.5 - 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 (A EOB ) 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 section Z - projectile atomic number S - projectile stopping power N A - Avogadro’s number H - isotopic enrichment of the target material TTY = HN A λ ZeM ∫ E min E max σ (E ) S ( E ) d E 43 Sc & 44m Sc/ 44 Sc α range in tissue = 55-77 µm cell size ≈ 10 µm α LET ≈ 100 keV/µm high 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: 99m Tc, 72 Se/ 72 As, 211 At, 43 Sc and 44m Sc/ 44 Sc 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 energy M - atomic mass of target λ - product decay constant e - electron charge 43 Sc 0 0 373 43 Ca 22% 78% 7/2- 5/2- 7/2- 3.9 h 99m Tc A 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 100 Mo(p,d+pn) 99 Mo and 100 Mo(p,2n) 99m Tc reactions: Estimation of long-lived Tc-impurity and its implication on the specific activity of cyclotron-produced 99m Tc. Appl. Radiat. Isot. 85, 101–113 72 Se/ 72 As 72 Se 0 46 100% 0+ 1+ 8.5 d 72 As 0 0 834 72 Ge 68% 17% 15% 2- 2+ 0+ 26 h α energy [MeV] 30 72 Se 0.19(3) 72 As 2.7(1) TTY [MBq/µAh] α energy [MeV] 29 30 31 211 At 37(6) 46(5) 55(7) 210 At 0.009(2) 0.06(1) 0.5(1) TTY [MBq/µAh] α + nat CaCO 3 & nat Ca metal 43 Sc production yield α + nat CaCO 3 (20 – 0 MeV) 4 h irradiation 43 Sc, 44 Sc = instead of 18 F, 68 Ga 44 Sc = three photon PET 44m Sc/ 44 Sc = in vivo generator 0 207 Bi 9/2- 33 y 0 211 At 9/2- 7.2 h 0 67.9 207 Pb 13/2+ 1/2- 100% 16% 84% 42% α 5.9 MeV 0 211 Po 9/2+ 0.5 s 0.8 s 58% 100% α 7.5 MeV One should avoid the formation of the dangerous 210 At by the (α,3n) reaction. TTY of 211 At and 210 At for 209 Bi target and different bombarding energies are shown below: The 211 At is one of the most promising α emitters for Targeted Alpha Therapy. Its production has been investigated using 209 Bi target (~98 mg/cm 2 ) 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 211 At at EOB can be produced. α + 209 Bi 211 At production yield α + 42 CaCO 3 (68%) 44 Sc & 44m Sc production yield α + 42 CaCO 3 68% (29 - 12 MeV) 12 h irradiation TTY [MBq/µAh] 84(4) 44(7) 4.7(8) isotope 43 Sc 44 Sc 44m Sc target nat CaCO 3 42 CaCO 3 42 CaCO 3 α energy [MeV] 20 29 29 The production of 43 Sc was investigated via the 40 Ca(α,p) using nat CaCO 3 and nat Ca metal targets (96.9% 40 Ca in nat Ca). The observed impurities level in the nat CaCO 3 (<0.05% of 43 Sc A EOB ) makes this production route extreme- ly attractive. The use of enriched 40 CaCO 3 (99.99% 40 Ca) yields impurities lower than 10 -5 % for over 15 h after the EOB. Also, irradiating the nat Ca metal with the α- beam of 25 µA (from commercially availa- ble cyclotron), a 14 GBq of 43 Sc at EOB could 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 44 Sc from a natural calcium target using adipentylpentylphosphonate functionalized extraction resin. Appl. Radiat. Isot. 95, 23 proton energy [MeV] 16-8 26-8 6 h irradiation, 40 µA: Long-lived impurities <0.02% EOB <0.03% EOB A EOB 99m Tc [GBq] 64 150 99m Tc 372(45) 865(65) 99 Mo 2.4(6) 31(5) TTY [MBq/µAh] 72 As via the 70 Ge(α,pn) reactions. With ir- radiation time 8 h and beam intensity 25 μA a 38 MBq A EOB of 72 Se/ 72 As generator could be produced. Assuming 100% chemical extraction effciency, 3 days after the EOB a 31 MBq and 15 α + nat GeO 2 72 Se & 72 As production yield A nat GeO 2 target was irradiated with a 30 MeV α-beam to produce 72 Se via the 70 Ge(α,2n) and long physiological processes investigations potential for PET where no cyclotron is available 72 Se/ 72 As = long-lived generator p + 100 Mo 99.815% (26 – 8 MeV) days after EOB a 13 MBq of 72 As can be extracted. To get 44 Sc and 44m Sc via the (α,pn) and (α,np) the enriched 42 CaCO 3 (68% 42 Ca) target was used. The results above were extrapolated for commercially available 95.9% enrichment. The production efficiency of 44 Sc for α is smaller than for proton or deuteron induced reactions. However, for 29 MeV α, the 44m Sc/ 44 Sc TTY ratio is Severin et al., 2012. Cyclotron Produced 44g Sc from Natural Calcium. Appl. Radiat. Isot. 70, 1526 6 h irradiation p + 100 Mo (99.815%) 99m Tc 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
Transcript of Production of and research on medical radioisotopes at the ... · Production of and research on...
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: [email protected]
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
