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Production, Purification, and Radiolabeling of the 203Pb/212Pb Theranostic Pair
Caterina Fortunata Ramogida
Simon Fraser University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-4815-2647
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This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at EJNMMI Radiopharmacy and Chemistry.
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-carbomoylmethyl)cyclododecane).
Results: Proton irradiation (12.8 MeV) of natural and enriched thalium-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.
Keywords
lead-212, lead-203, thorium-228 generator, thallium-203, theranostic, cyclen, DOTA, pyridyl, chelators, radiolabeling
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CURRENT STATUS: Published
Version 1
Posted 01 Dec, 2020
Published
On 01 Feb, 2021
No community comments so far
Editorial decision: Minor revision
On 10 Dec, 2020
Review #2 received
Received 05 Dec, 2020
Review #1 received
Received 02 Dec, 2020
Reviewer #3 agreed
On 25 Nov, 2020
Reviewer #2 agreed
On 23 Nov, 2020
Editor assigned
On 22 Nov, 2020
Reviewers invited
Invitations sent on 22 Nov, 2020
Reviewer #1 agreed
On 22 Nov, 2020
Editor invited
On 22 Nov, 2020
Submission checks complete
On 22 Nov, 2020
First submitted
On 18 Nov, 2020
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Subject Areas
General Biochemistry
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This preprint is under consideration at EJNMMI Radiopharmacy and Chemistry. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Production, Purification, and Radiolabeling of the 203Pb/212Pb Theranostic Pair
Caterina Fortunata Ramogida
Simon Fraser University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-4815-2647
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 1
Posted 01 Dec, 2020
Published
On 01 Feb, 2021
No community comments so far
Editorial decision: Minor revision
On 10 Dec, 2020
Review #2 received
Received 05 Dec, 2020
Review #1 received
Received 02 Dec, 2020
Reviewer #3 agreed
On 25 Nov, 2020
Reviewer #2 agreed
On 23 Nov, 2020
Editor assigned
On 22 Nov, 2020
Reviewers invited
Invitations sent on 22 Nov, 2020
Reviewer #1 agreed
On 22 Nov, 2020
Editor invited
On 22 Nov, 2020
Submission checks complete
On 22 Nov, 2020
First submitted
On 18 Nov, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
General Biochemistry
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at EJNMMI Radiopharmacy and Chemistry.
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-carbomoylmethyl)cyclododecane).
Results: Proton irradiation (12.8 MeV) of natural and enriched thalium-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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the manuscript can be downloaded and accessed as a PDF.