Journal of Nuclear Science, Engineering and Technology (JONSAT)
In cooperation with the Iranian Nuclear Society

Production and quality control of the 132/135La theranostic pair for targeted radiotherapy

Document Type : Research Paper

Authors

A. Shirpoor 1
A. Haddadi 1
S. Zolghadri 2
S. Vosoughi 2
S. Rajabifar 2

1 Medical Radiation Engineering Department, Science and Research Branch, Islamic Azad University, P.O.Box: 14515-775, Tehran – Iran

2 Radiation Application Research School, Nuclear Science and Technology Research Institute, AEOI, P.O.Box: 14395-836, Tehran - Iran

https://doi.org/10.24200/nst.2024.1646.2045
Abstract
Among promising radioisotopes, 132/135La stands out as a theranostic pair, offering specific advantages for the preparation of a wide range of radiopharmaceuticals. In this study, the theranostic pair 132/135La was produced through the interaction of natBa(p,x)13xLa, using theoretical calculations with the nuclear codes ALICE-91, TALYS-1.8, and SRIM-2013. The natural barium target was then irradiated in a 30 MeV cyclotron with 22.5 MeV protons and a current of 100 μAh. After the lanthanum was separated from the irradiated target, the solution's chemical purity, radiochemical purity, and radionuclide purity were examined using ICP-OES, RTLC, and gamma spectrometry, respectively. The study also investigated the effect of increasing the concentration of the chelator DOTA (1-100 nanomolar) on its labeling with lanthanum. The results showed that the average total amount of metal ions in the final solution was less than 0.1 ppm, with radiochemical and radionuclide purities above 99% and 99.5%, respectively. The labeling of the chelator DOTA with lanthanum demonstrated that even with the addition of 1 nmol of this chelator, a radiochemical purity higher than 93% was achieved. This study indicates that it is possible to produce lanthanum radionuclides with the required quality for the development of theranostic radiopharmaceuticals.

Highlights

  1. Center M.M, Siegel R, Jemal A. Global cancer facts & figures. Atlanta: American Cancer Society. 2011;1-52.

 

  1. Curcio C.G, Vasile C, Gianciotta A, Casali A, Gionfra T, Rinaldi M, Guadagni A, Le Pera V, Sega E. Short-term results of combined radioimmunotherapy in inoperable lung cancer. Tumori Journal. 1976 Nov;62(6):587-97.

 

  1. Nelson B.J, Wilson J, Andersson J.D, Wuest F. High yield cyclotron production of a novel 133/135La theranostic pair for nuclear medicine. Scientific Reports. 2020 Dec 17;10(1):22203.

 

  1. Chakravarty R, Patra S, Jagadeesan K.C, Thakare S.V, Chakraborty S. Electrochemical separation of 132/135La theranostic pair from proton irradiated Ba target. Separation and Purification Technology. 2022 Jan 1;280:119908.

 

  1. Lessing J.G, Fouche K.F. Separation of carrier-free rhodium-105 from neutron-irradiated ruthenium by extraction from molten cyanide. Analytical Chemistry. 1975 Jan 1;47(1):182-4.

 

  1. Grudzinski J, Marsh I, Titz B, Jeffery J, Longino M, Kozak K, Lange K, Larrabee J, Weichmann A, Moser A, Bednarz B. CLR 125 Auger electrons for the targeted radiotherapy of triple-negative breast cancer. Cancer Biotherapy & Radiopharmaceuticals. 2018 Apr 1;33(3):87-95.

 

  1. Tavares A.A, Tavares J.M. 99mTc Auger electrons for targeted tumour therapy: A review. International journal of radiation biology. 2010 Apr 1;86(4):261-70.

 

  1. Thisgaard H, Halle B, Aaberg-Jessen C, Olsen B.B, Therkelsen A.S, Dam J.H, Langkjær N, Munthe S, Någren K, Høilund-Carlsen P.F, Kristensen B.W. Highly effective auger-electron therapy in an orthotopic glioblastoma xenograft model using convection-enhanced delivery. Theranostics. 2016;6(12):2278.

 

  1. Aluicio-Sarduy E, Hernandez R, Olson A.P, Barnhart T.E, Cai W, Ellison P.A, Engle J.W. Production and in vivo PET/CT imaging of the theranostic pair 132/135La. Scientific reports. 2019 Jul 23;9(1):10658.

 

  1. Fonslet J, Lee B.Q, Tran T.A, Siragusa M, Jensen M, Kibedi T, Stuchbery A.E, Severin G.W. 135La as an Auger-electron emitter for targeted internal radiotherapy. Physics in Medicine & Biology. 2017 Dec 29;63(1):015026.

 

  1. Mansel A, Franke K. Production of no-carrier-added 135La at an 18 MeV cyclotron and its purification for investigations at a concentration range down to 10− 15 mol/L. Radiochimica Acta. 2015 Nov 28;103(11):759-63.

 

  1. Jagodić V, Herak M.J, Radošević J. Separation of lanthanum from barium by solvent extraction with the monooctyl ester of anilinobenzylphosphonic acid. Journal of the Less Common Metals. 1968 Aug 1;15(4):371-5.

 

  1. Perkins R.W. Filtration-precipitation separation of barium-140 from lanthanum-140. Analytical Chemistry. 1957 Jan 1;29(1):152-3.

 

  1. Möller T, Bestaoui N, Wierzbicki M, Adams T, Clearfield A. Separation of lanthanum, hafnium, barium and radiotracers yttrium-88 and barium-133 using crystalline zirconium phosphate and phosphonate compounds as prospective materials for a Ra-223 radioisotope generator. Applied Radiation and Isotopes. 2011 Jul 1;69(7):947-54.

 

  1. Das N.R, Bhattacharyya S.N. Ion exchange separation of carrier-free 140Ba and 140La from their equilibrium mixture using nitrilotriacetic acid and ascorbic acid as eluents. The International Journal of Applied Radiation and Isotopes. 1982 Mar 1;33(3):171-3.

 

  1. Bhattacharyya D.K, Basu S. Use of Alumina as an Ion Exchanger in the Separation of Carrier-Free 140La from 140Ba. Separation Science and Technology. 1976 Jan 1;11(1):103-8.

 

  1. Yousefnia H, Zolghadri S, Shanehsazzadeh S. Estimated human absorbed dose of 177Lu–BPAMD based on mice data: Comparison with 177Lu–EDTMP. Applied Radiation and Isotopes. 2015 Oct 1; 104:128-35.

Keywords

Theranostic
132/135La
Radiochemical separation
Labeling
DOTA chelator
  1. Center M.M, Siegel R, Jemal A. Global cancer facts & figures. Atlanta: American Cancer Society. 2011;1-52.

 

  1. Curcio C.G, Vasile C, Gianciotta A, Casali A, Gionfra T, Rinaldi M, Guadagni A, Le Pera V, Sega E. Short-term results of combined radioimmunotherapy in inoperable lung cancer. Tumori Journal. 1976 Nov;62(6):587-97.

 

  1. Nelson B.J, Wilson J, Andersson J.D, Wuest F. High yield cyclotron production of a novel 133/135La theranostic pair for nuclear medicine. Scientific Reports. 2020 Dec 17;10(1):22203.

 

  1. Chakravarty R, Patra S, Jagadeesan K.C, Thakare S.V, Chakraborty S. Electrochemical separation of 132/135La theranostic pair from proton irradiated Ba target. Separation and Purification Technology. 2022 Jan 1;280:119908.

 

  1. Lessing J.G, Fouche K.F. Separation of carrier-free rhodium-105 from neutron-irradiated ruthenium by extraction from molten cyanide. Analytical Chemistry. 1975 Jan 1;47(1):182-4.

 

  1. Grudzinski J, Marsh I, Titz B, Jeffery J, Longino M, Kozak K, Lange K, Larrabee J, Weichmann A, Moser A, Bednarz B. CLR 125 Auger electrons for the targeted radiotherapy of triple-negative breast cancer. Cancer Biotherapy & Radiopharmaceuticals. 2018 Apr 1;33(3):87-95.

 

  1. Tavares A.A, Tavares J.M. 99mTc Auger electrons for targeted tumour therapy: A review. International journal of radiation biology. 2010 Apr 1;86(4):261-70.

 

  1. Thisgaard H, Halle B, Aaberg-Jessen C, Olsen B.B, Therkelsen A.S, Dam J.H, Langkjær N, Munthe S, Någren K, Høilund-Carlsen P.F, Kristensen B.W. Highly effective auger-electron therapy in an orthotopic glioblastoma xenograft model using convection-enhanced delivery. Theranostics. 2016;6(12):2278.

 

  1. Aluicio-Sarduy E, Hernandez R, Olson A.P, Barnhart T.E, Cai W, Ellison P.A, Engle J.W. Production and in vivo PET/CT imaging of the theranostic pair 132/135La. Scientific reports. 2019 Jul 23;9(1):10658.

 

  1. Fonslet J, Lee B.Q, Tran T.A, Siragusa M, Jensen M, Kibedi T, Stuchbery A.E, Severin G.W. 135La as an Auger-electron emitter for targeted internal radiotherapy. Physics in Medicine & Biology. 2017 Dec 29;63(1):015026.

 

  1. Mansel A, Franke K. Production of no-carrier-added 135La at an 18 MeV cyclotron and its purification for investigations at a concentration range down to 10− 15 mol/L. Radiochimica Acta. 2015 Nov 28;103(11):759-63.

 

  1. Jagodić V, Herak M.J, Radošević J. Separation of lanthanum from barium by solvent extraction with the monooctyl ester of anilinobenzylphosphonic acid. Journal of the Less Common Metals. 1968 Aug 1;15(4):371-5.

 

  1. Perkins R.W. Filtration-precipitation separation of barium-140 from lanthanum-140. Analytical Chemistry. 1957 Jan 1;29(1):152-3.

 

  1. Möller T, Bestaoui N, Wierzbicki M, Adams T, Clearfield A. Separation of lanthanum, hafnium, barium and radiotracers yttrium-88 and barium-133 using crystalline zirconium phosphate and phosphonate compounds as prospective materials for a Ra-223 radioisotope generator. Applied Radiation and Isotopes. 2011 Jul 1;69(7):947-54.

 

  1. Das N.R, Bhattacharyya S.N. Ion exchange separation of carrier-free 140Ba and 140La from their equilibrium mixture using nitrilotriacetic acid and ascorbic acid as eluents. The International Journal of Applied Radiation and Isotopes. 1982 Mar 1;33(3):171-3.

 

  1. Bhattacharyya D.K, Basu S. Use of Alumina as an Ion Exchanger in the Separation of Carrier-Free 140La from 140Ba. Separation Science and Technology. 1976 Jan 1;11(1):103-8.

 

  1. Yousefnia H, Zolghadri S, Shanehsazzadeh S. Estimated human absorbed dose of 177Lu–BPAMD based on mice data: Comparison with 177Lu–EDTMP. Applied Radiation and Isotopes. 2015 Oct 1; 104:128-35.

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