CYCLOTRON PRODUCTION FOR RADIOMETAL OF ZIRCONIUM-89...
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CONCLUSIONS: The production of 89 Zr with a Cyclone 18/9 and COSTIS STS is possible. It is necessary to wait at least 4 hours before measuring the activity and decay correct in order to calculate the 89g Zr activity at the end of cyclotron production (fig 5). Degrading the proton beam to 10 MeV produces radionuclidically pure 89 Zr. Whilst this is enough for pre-clinical use, the yield is not enough for either clinical use or commercial supply. Using thinner beam degraders to increase the proton beam energy increases the radionuclidic yield but it is not yet possible to exclude the presence of radionuclidic impurities. REFERENCES: 1) T. J. Wadas, E. H. Wong, G. R. Weisman and C. J. Anderson, Chemical Reviews 110, 2858-2902 (2010). 2) M. A. Avila-Rodriguez, J. Rajander, J. O. Lill, K. Gagnon, J. Schlesinger, J.S. Wilson, S.A. McQuarrie, O. Solin, Nucl. Instr. Met. Phys. Res. Sect. B 267, 1867-1872 (2009). 3) M. Walther, P Gebhardt, P. Grosse-Gehling, L. Würbach, I. Irmler,S. Preusche, M. Khalid, T. Opfermann, T. Kamradt, J. Steinbach, H. P. Saluz, Appl. Rad. and Isotopes 69, 852-857 (2011). 4) Elex Commerce, COSTIS - Operating Manual, TS04-80.00.00.01, 2007. CYCLOTRON PRODUCTION FOR RADIOMETAL OF ZIRCONIUM-89 IN PETIC WITH IBA CYCLONE 18/9 AND COSTIS SOLID TARGET SYSTEM Adam Dabkowski, Katrin Probst, Christopher Marshall PETIC, School of Medicine, Cardiff University, Cardiff, United Kingdom RESULTS: • Degradation of energy by means of both 0.4mm & 0.5 mm thick Nb foil was achieved & did not suffer from overheating problems at long irradiation times (2-3 h) • From repeated measurements of activity (fig 5), it is clear that there is a bi-exponential decay of radioactivity due to the short lived 89m Zr and 89 Zr. The measured half life of the longer lived radionulide was 78.841 hours •The energy spectrum from 89 Zr produced using Nb foil thickness of 0.5 mm (Fig 4) has energy peaks at 511 keV and 909 keV consistent with 89 Zr •Production of 89 Zr with 500 μm thick Nb (E = 9.8 MeV) was achieved, without producing either 88 Zr or 88 Y (fig 4) & resulted in yields of (8 - 9 MBq/μAh) – tab 2 •Production of 89 Zr with 400 μm thick Nb (E = 11.6 MeV) results in a higher yield (14-16 MBq/μAh). However, it is not yet possible to exclude the presence of long lived impurities as there has been insufficient time to allow for the decay of 89 Zr. 14 th International Workshop on Targetry and Target Chemistry, Riviera Maya, Quintana Roo, Mexico – August 2012 Figure 2: Aluminium solid target holder with 89 Y target foil. INTRODUCTION: The development of biological targeting agents such as proteins, peptides, antibodies and nanoparticles with a range of biological half lives demands the production of new radionuclides with half-lives complementary to these biological properties 1) . Zirconium-89 ( 89 Zr) is a promising radionuclide for development of new immuno-PET agents due to it’s convenient half life of 78.4 h, β+ emission rate of 23%, low maximum energy of 0.9 MeV resulting in a good spatial resolution, a stable daughter Yttrium-89 ( 89 Y) and favorable imaging characteristics with only one significant γ-line of 909 keV emitted during decay alongside the 511 keV positron photons. Three nuclear reactions have been explored for the production of Zr-89. PETIC is unequipped to perform either the nat Sr(α,xn) 89 Zr or 89 Y(d,2n) 89 Zr reactions. The proton energy for the 89 Y(p,n) 89 Zr reaction with reasonable yield is 10-15 MeV 2) , with a maximum nuclear cross section at ≈12 MeV, enabling the reaction to be performed in PETIC’s IBA 18/9 cyclotron equipped with a COSTIS Solid Target System (STS). An advantage of the 89 Y(p,n) 89 Zr reaction is that 89 Y is the only stable isotope of Yttrium, negating the need for isotopic purification of the target material. However, long lived radionuclidic impurities may be generated by the competing nuclear reactions 89 Y(p,2n) 88 Zr (Threshold 13.076 MeV) and 89 Y(p,pn) 88 Y (Threshold 11.609 MeV) in low energy cyclotrons. Both of these radioisotopes could significantly increase the radiation dose to the patient if they were present in the final product. Therefore, both of these production pathways need to be accounted for, and minimised, when producing 89 Zr. Our aim was to prove that isotopically pure 89 Zr could be produced in an IBA 18/9 cyclotron equipped with a COSTIS Solid Target System and then optimise the yield by reducing the beam degrader thickness without producing either 88 Zr or 88 Y. MATERIAL AND METHODS: The target material 89 Y was obtained as a 150 μm thick foil (Isotopic purity ≈ 99.9 %, Goodfellow Cambridge Ltd) (fig 2 - photograph). The solid target used in PETIC was based on the design described by Walther et al 3) (fig 2). The proton beam of Cyclone 18/9 cyclotron was degraded from 18 MeV to ≈9.8 and ≈11.6 MeV first by the 0.5 mm thick and then by 0.4 mm thick Niobium window foil (fig 1) (Goodfellow Cambridge Ltd) installed in the COSTIS STS 4) . The activity of the 89 Zr produced was measured using a CRC 25R Capintec Dose Calibrator set to a dial factor of 465, 4 hours after the end of beam to allow for the decay of short lived 89m Zr which is also produced alongside 89 Zr and decay corrected to End of Beam. Long lived impurities were assessed using an Ortec (NaI) Multi Channel Analyser. 89 Y(p,n) 89 Zr 89 Y(d,2n) 89 Zr nat Sr(α,xn) 89 Zr Figure 1: Used Niobium vacuum window for the beam energy degradation (note the dark spot - bam position). Table 1: Nuclear reactions for Zr-89 production. Figure 3: Tool designed for the coin opening with tong-gators. Figure 4: Energy spectrum from 89 Zr production with 0.5 mm thick Niobium beam degrader shows the characteristic 511 and 909 keV gamma emissions from 89 Zr. Beam Time [h] Beam Current [uA] Niobium Thickness [μm] Beam Energy [MeV] Product [uAh] 89g Zr Activity EOB [MBq] Average Yield of the 89 Y(p,n) 89 Zr nuclear reaction [MBq/uAh] 3 20 500 9.8 60 529.5 8.83 3 30 500 9.8 90 791.7 8.79 2.1 30 400 11.6 63 973.4 15.45 1.5 20 400 11.6 30 445 14.83 3 30 400 11.6 90 1400 15.56 Table 2: Zr-89 productions parameters and yields. Figure 5: Early and delayed measurements of activity from 89 Zr production with 0.5 mm thick Niobium beam degrader showing that good base for 89g Zr activity extrapolation constitute delayed measurements after 4h from EOB.
Transcript of CYCLOTRON PRODUCTION FOR RADIOMETAL OF ZIRCONIUM-89...
CONCLUSIONS: The production of 89Zr with a Cyclone 18/9 and COSTIS STS is possible. It is necessary to wait at least 4 hours before measuring the activity and
decay correct in order to calculate the 89gZr activity at the end of cyclotron production (fig 5). Degrading the proton beam to 10 MeV produces radionuclidically pure 89Zr. Whilst this is enough for pre-clinical use, the yield is not enough for either clinical use or commercial supply. Using thinner beam degraders to increase the proton beam energy increases the radionuclidic yield but it is not yet possible to exclude the presence of radionuclidic impurities.
REFERENCES: 1) T. J. Wadas, E. H. Wong, G. R. Weisman and C. J. Anderson, Chemical Reviews 110, 2858-2902 (2010). 2) M. A. Avila-Rodriguez, J. Rajander,
J. O. Lill, K. Gagnon, J. Schlesinger, J.S. Wilson, S.A. McQuarrie, O. Solin, Nucl. Instr. Met. Phys. Res. Sect. B 267, 1867-1872 (2009). 3) M. Walther, P Gebhardt, P. Grosse-Gehling, L. Würbach, I. Irmler,S. Preusche, M. Khalid, T. Opfermann, T. Kamradt, J. Steinbach, H. P. Saluz, Appl. Rad. and Isotopes 69, 852-857 (2011). 4) Elex Commerce, COSTIS - Operating Manual, TS04-80.00.00.01, 2007.
CYCLOTRON PRODUCTION FOR RADIOMETAL OF
ZIRCONIUM-89 IN PETIC WITH IBA CYCLONE 18/9 AND
COSTIS SOLID TARGET SYSTEM
Adam Dabkowski, Katrin Probst, Christopher Marshall
PETIC, School of Medicine, Cardiff University, Cardiff, United Kingdom
RESULTS:
• Degradation of energy by means of both 0.4mm & 0.5 mm thick Nb foil was achieved & did not suffer from overheating problems at long irradiation times (2-3 h)
• From repeated measurements of activity (fig 5), it is clear that there is a bi-exponential decay of radioactivity due to the short lived 89mZr and 89Zr. The measured half life of the longer lived radionulide was 78.841 hours
•The energy spectrum from 89Zr produced using Nb foil thickness of 0.5 mm (Fig 4) has energy peaks at 511 keV and 909 keV consistent with 89Zr
•Production of 89Zr with 500 µm thick Nb (E = 9.8 MeV) was achieved, without producing either 88Zr or 88Y (fig 4) & resulted in yields of (8 - 9 MBq/µAh) – tab 2
•Production of 89Zr with 400 µm thick Nb (E = 11.6 MeV) results in a higher yield (14-16 MBq/µAh). However, it is not yet possible to exclude the presence of long lived impurities as there has been insufficient time to allow for the decay of 89Zr.
14th International Workshop on Targetry and Target Chemistry, Riviera Maya, Quintana Roo, Mexico – August 2012
Figure 2: Aluminium solid target holder
with 89Y target foil.
INTRODUCTION: The development of biological targeting agents such as proteins, peptides, antibodies and nanoparticles with a range of biological half lives demands the production of new radionuclides with half-lives complementary to these biological properties1). Zirconium-89 (89Zr) is a promising radionuclide for
development of new immuno-PET agents due to it’s convenient half life of 78.4 h, β+ emission rate of 23%, low maximum energy of 0.9 MeV resulting in a good spatial resolution, a stable daughter Yttrium-89 (89Y) and favorable imaging characteristics with only one significant γ-line of 909 keV emitted during decay alongside the 511 keV positron photons.
Three nuclear reactions have been explored for the production of Zr-89. PETIC is unequipped to perform either the natSr(α,xn)89Zr or 89Y(d,2n)89Zr reactions. The proton energy for the 89Y(p,n) 89Zr reaction with reasonable yield is 10-15 MeV2), with a maximum nuclear cross section at ≈12 MeV, enabling the reaction to be performed in PETIC’s IBA 18/9 cyclotron equipped with a COSTIS Solid Target System (STS).
An advantage of the 89Y(p,n)89Zr reaction is that 89Y is the only stable isotope of Yttrium, negating the need for isotopic purification of the target material. However, long lived radionuclidic impurities may be generated by the competing nuclear reactions 89Y(p,2n)88Zr (Threshold 13.076 MeV) and 89Y(p,pn)88Y (Threshold 11.609 MeV) in low energy cyclotrons. Both of these radioisotopes could significantly increase the radiation dose to the patient if they were present in
the final product. Therefore, both of these production pathways need to be accounted for, and minimised, when producing 89Zr.
Our aim was to prove that isotopically pure 89Zr could be produced in an IBA 18/9 cyclotron equipped with a COSTIS Solid Target System and then optimise the yield by reducing the beam degrader thickness without producing either 88Zr or 88Y.
MATERIAL AND METHODS: The target material 89Y was obtained as a 150 µm thick foil (Isotopic purity ≈ 99.9 %, Goodfellow Cambridge Ltd) (fig 2 -photograph). The solid target used in PETIC was based on the design described by Walther et al3) (fig 2). The proton beam of Cyclone 18/9 cyclotron was
degraded from 18 MeV to ≈9.8 and ≈11.6 MeV first by the 0.5 mm thick and then by 0.4 mm thick Niobium window foil (fig 1) (Goodfellow Cambridge Ltd) installed in the COSTIS STS4). The activity of the 89Zr produced was measured using a CRC 25R Capintec Dose Calibrator set to a dial factor of 465, 4 hours after the end of beam to allow for the decay of short lived 89mZr which is also produced alongside 89Zr and decay corrected to End of Beam. Long lived impurities were assessed using an Ortec (NaI) Multi Channel Analyser.
89Y(p,n)89Zr89Y(d,2n)89Zr
natSr(αααα,xn)89Zr
Figure 1: Used Niobium vacuum window for
the beam energy degradation (note the dark
spot - bam position).
Table 1: Nuclear reactions for Zr-89 production.
Figure 3: Tool designed for the coin opening with tong-gators.
Figure 4: Energy spectrum from 89Zr production with 0.5 mm thick
Niobium beam degrader shows the characteristic 511 and 909 keV gamma
emissions from 89Zr.
Beam Time [h]Beam Current
[uA]
Niobium
Thickness [µµµµm]
Beam Energy
[MeV]Product [uAh]
89g Zr Activity EOB
[MBq]
Average Yield of the 89Y(p,n)89Zr nuclear reaction [MBq/uAh]
3 20 500 9.8 60 529.5 8.83
3 30 500 9.8 90 791.7 8.79
2.1 30 400 11.6 63 973.4 15.45
1.5 20 400 11.6 30 445 14.83
3 30 400 11.6 90 1400 15.56
Table 2: Zr-89 productions parameters and yields.
Figure 5: Early and delayed measurements of activity from 89Zr production with 0.5 mm
thick Niobium beam degrader showing that good base for 89gZr activity extrapolation
constitute delayed measurements after 4h from EOB.
