Optimized production, purification, and radiolabeling of the 203Pb/212Pb theranostic pair for nuclear medicine
Brooke L. McNeil, Simona A. Mastroianni, Scott McNeil, Stefan Zeisler, Joel Kumlin, Sogol Borjian, Anthony W. McDonagh, Michael Cross, Paul Schaffer, Caterina F. Ramogida
Abstract
Abstract TRIUMF is one of the only laboratories in the world able to produce both lead-203 ( 203 Pb, t 1/2 = 51.9 h) and 212 Pb (t 1/2 = 10.6 h) onsite via its 13 and 500 MeV cyclotrons, respectively. Together, 203 Pb and 212 Pb form an element-equivalent theranostic pair that potentiate image-guided, personalized cancer treatment, using 203 Pb as a single-photon emission computed tomography (SPECT) source, and 212 Pb for targeted alpha therapy. In this study, improvements to 203 Pb production were accomplished by manufacturing electroplated, silver-backed thallium (Tl) targets to improve target thermal stability, which allow for higher currents during irradiation. We implemented a novel, two-column purification method that employs selective Tl precipitation ( 203 Pb only) alongside extraction and anion exchange chromatography to elute high specific activity and chemical purity 203/212 Pb in a minimal volume of dilute acid, without the need for evaporation. Optimization of the purification method translated to improvements in radiolabeling yields and apparent molar activity of lead chelators TCMC (S-2-(4-Isothiocyanatobenzyl)-1,4,7,10-tetraaza-1,4,7,10-tetra(2-carbamoylmethyl)cyclododecane) and Crypt-OH, a derivative of a [2.2.2]-cryptand.