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Background  Lead-212 ( 212 Pb, t 1/2  = 10.6 h) and lead-203 ( 203 Pb, t 1/2  = 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  203 Pb and  212 Pb 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 ( 203 Tl) targets gave  203 Pb saturation yields of 134 ± 25 and 483 ± 3 MBq/μA, respectively. Thorium-228 ( 228 Th, t 1/2  = 1.9 y), a by-product of  232 Th proton spallation on TRIUMF’s main 500 MeV beamline (beamline 1A, BL1A), was recovered to build a  228 Th/ 212 Pb generator with the ability to deliver up to 9–10 MBq of  212 Pb daily. Both lead isotopes were purified via solid phase extraction chromatography (Pb resin), and isolated in an acetate form ([ 203/212 Pb]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  203 Pb and  212 Pb. All chelates incorporated  212 Pb/ 203 Pb efficiently, with higher radiolabeling yields observed for the  212 Pb-complexes.    Conclusion  The production of  203 Pb and  212 Pb 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  212 Pb/ 203 Pb studies.    Supplementary Information  The online version contains supplementary material available at 10.1186/s41181-021-00121-4.

Production, purification, and radiolabeling of the 203Pb/212Pb theranostic pair