Brooke L McNeil1,2, Andrew K H Robertson1,3, Winnie Fu1, Hua Yang1, Cornelia Hoehr1, Caterina F Ramogida4,5, Paul Schaffer6,7,8. 1. Life Sciences Division, TRIUMF, Vancouver, BC, Canada. 2. Department of Chemistry, Simon Fraser University, Burnaby, BC, Canada. 3. Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada. 4. Life Sciences Division, TRIUMF, Vancouver, BC, Canada. cfr@sfu.ca. 5. Department of Chemistry, Simon Fraser University, Burnaby, BC, Canada. cfr@sfu.ca. 6. Life Sciences Division, TRIUMF, Vancouver, BC, Canada. pschaffer@triumf.ca. 7. Department of Chemistry, Simon Fraser University, Burnaby, BC, Canada. pschaffer@triumf.ca. 8. Department of Radiology, University of British Columbia, Vancouver, BC, Canada. pschaffer@triumf.ca.
Abstract
BACKGROUND: Lead-212 (212Pb, t1/2 = 10.6 h) and lead-203 (203Pb, t1/2 = 51.9 h) are an element-equivalent, or a matched theranostic radioisotope pair that show great potential for application in targeted radionuclide therapy (TRT) and single-photon emission computed tomography (SPECT), respectively. At TRIUMF we have produced both 203Pb and 212Pb using TRIUMF's TR13 (13 MeV) and 500 MeV cyclotrons, and subsequently purified and evaluated both radioisotopes using a series of pyridine-modified DOTA analogues in comparison to the commercially available chelates DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and TCMC (1,4,7,10-tetraaza-1,4,7,10-tetra(2-carbamoylmethyl)cyclododecane). RESULTS: Proton irradiation (12.8 MeV) of natural and enriched thallium-203 (203Tl) targets gave 203Pb saturation yields of 134 ± 25 and 483 ± 3 MBq/μA, respectively. Thorium-228 (228Th, t1/2 = 1.9 y), a by-product of 232Th proton spallation on TRIUMF's main 500 MeV beamline (beamline 1A, BL1A), was recovered to build a 228Th/212Pb generator with the ability to deliver up to 9-10 MBq of 212Pb daily. Both lead isotopes were purified via solid phase extraction chromatography (Pb resin), and isolated in an acetate form ([203/212Pb]Pb(OAc)2) suitable for direct radiolabeling of chelators and bioconjugates. A series of cyclen-based chelators (herein referred to as DOTA-1Py, -2Py, and -3Py) along with established chelates DOTA and TCMC were evaluated for their ability to complex both 203Pb and 212Pb. All chelates incorporated 212Pb/203Pb efficiently, with higher radiolabeling yields observed for the 212Pb-complexes. CONCLUSION: The production of 203Pb and 212Pb was established using TRIUMF 13 MeV and 500 MeV cyclotrons, respectively. Both production methods provided radiometals suitable for subsequent radiolabeling reactions using known and novel chelates. Furthermore, the novel chelate DOTA-3Py may be a good candidate for biomolecule conjugation and further theranostic 212Pb/203Pb studies.
BACKGROUND: Lead-212 (212Pb, t1/2 = 10.6 h) and lead-203 (203Pb, t1/2 = 51.9 h) are an element-equivalent, or a matched theranostic radioisotope pair that show great potential for application in targeted radionuclide therapy (TRT) and single-photon emission computed tomography (SPECT), respectively. At TRIUMF we have produced both 203Pb and 212Pb using TRIUMF's TR13 (13 MeV) and 500 MeV cyclotrons, and subsequently purified and evaluated both radioisotopes using a series of pyridine-modified DOTA analogues in comparison to the commercially available chelates DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and TCMC (1,4,7,10-tetraaza-1,4,7,10-tetra(2-carbamoylmethyl)cyclododecane). RESULTS: Proton irradiation (12.8 MeV) of natural and enriched thallium-203 (203Tl) targets gave 203Pb saturation yields of 134 ± 25 and 483 ± 3 MBq/μA, respectively. Thorium-228 (228Th, t1/2 = 1.9 y), a by-product of 232Th proton spallation on TRIUMF's main 500 MeV beamline (beamline 1A, BL1A), was recovered to build a 228Th/212Pb generator with the ability to deliver up to 9-10 MBq of 212Pb daily. Both lead isotopes were purified via solid phase extraction chromatography (Pb resin), and isolated in an acetate form ([203/212Pb]Pb(OAc)2) suitable for direct radiolabeling of chelators and bioconjugates. A series of cyclen-based chelators (herein referred to as DOTA-1Py, -2Py, and -3Py) along with established chelates DOTA and TCMC were evaluated for their ability to complex both 203Pb and 212Pb. All chelates incorporated 212Pb/203Pb efficiently, with higher radiolabeling yields observed for the 212Pb-complexes. CONCLUSION: The production of 203Pb and 212Pb was established using TRIUMF 13 MeV and 500 MeV cyclotrons, respectively. Both production methods provided radiometals suitable for subsequent radiolabeling reactions using known and novel chelates. Furthermore, the novel chelate DOTA-3Py may be a good candidate for biomolecule conjugation and further theranostic 212Pb/203Pb studies.
Authors: Kayhan Garmestani; Diane E Milenic; Erik D Brady; Paul S Plascjak; Martin W Brechbiel Journal: Nucl Med Biol Date: 2005-04 Impact factor: 2.408
Authors: Jun Young Lee; Jung Ho Chae; Min Goo Hur; Seung Dae Yang; Young Bae Kong; Jongchul Lee; Jin Sik Ju; Pyeong Seok Choi; Jeong Hoon Park Journal: Front Med (Lausanne) Date: 2022-05-18
Authors: Hua Yang; Justin J Wilson; Chris Orvig; Yawen Li; D Scott Wilbur; Caterina F Ramogida; Valery Radchenko; Paul Schaffer Journal: J Nucl Med Date: 2021-09-09 Impact factor: 11.082
Authors: Valery Radchenko; Alfred Morgenstern; Amir R Jalilian; Caterina F Ramogida; Cathy Cutler; Charlotte Duchemin; Cornelia Hoehr; Ferrid Haddad; Frank Bruchertseifer; Haavar Gausemel; Hua Yang; Joao Alberto Osso; Kohshin Washiyama; Kenneth Czerwinski; Kirsten Leufgen; Marek Pruszyński; Olga Valzdorf; Patrick Causey; Paul Schaffer; Randy Perron; Samsonov Maxim; D Scott Wilbur; Thierry Stora; Yawen Li Journal: J Nucl Med Date: 2021-07-22 Impact factor: 11.082
Authors: Konstantin V Kokov; Bayirta V Egorova; Marina N German; Ilya D Klabukov; Michael E Krasheninnikov; Antonius A Larkin-Kondrov; Kseniya A Makoveeva; Michael V Ovchinnikov; Maria V Sidorova; Dmitry Y Chuvilin Journal: Pharmaceutics Date: 2022-01-13 Impact factor: 6.321