![]() ![]() 203Pb is produced from the proton bombardment of Tl targets. In the case of cyclotron produced isotopes, it is also ideal to enable recycling of the expensive enriched target material included in the purification process to reduce costs.Ģ03Pb production, particularly on a 13 MeV cyclotron like at TRIUMF, poses many challenges. The desired radiometal should then be eluted in a small volume of dilute acid or buffer solution to help minimize the mass of radiopharmaceutical precursor needed for labeling. In an ideal purification procedure, one should avoid the use of several columns and evaporation steps to help simplify automation and reduce risk of material loss, while utilizing a column that will remove the bulk contaminant while the isotope of interest remains bound until elution. For cyclotron produced isotopes, for example 203Pb, the greatest chemical impurity is often the target material 9, mandating effective separation chemistry. Therefore, improving the chemical purity of the radiometal solution, and thus increasing the specific activity, is critical for advancement of TRPs. A low A m can affect kinetics and uptake at the tumour site and can lead to poor scan quality or low therapeutic effect 8. Competition with the radiometal can lower radiochemical yields (RCYs) and thus apparent molar activity (A m) of the radiopharmaceutical. Stable (non-radioactive) metal impurities in the radiometal solution can interfere with radiolabeling and, depending on the selectivity of the chelator, may be coordinated by the chelator. Due to its longer half-life compared to its daughters, the use of 212Pb allows for increased radiopharmaceutical preparation time.Īlthough all components of BFC-based radiopharmaceuticals affect the success of TRPs, the importance of the specific activity of the radiometal, which refers to the amount of measured activity per unit mass of compound, is often overlooked 7. Despite 212Pb being a pure β-emitter, it is used for targeted alpha therapy as it acts as an in vivo generator of its alpha emitting daughters 212Bi (t 1/2 = 60.5 min, E α avg = 6.2 MeV, 36%) and 212Po (t 1/2 = 0.3 μs, E α avg = 8.9 MeV, Fig. ![]() ![]() 212Pb acts as a therapeutic isotope in this pair. 203Pb is a diagnostic isotope that decays via electron capture, releasing a 279 keV photon (81%) compatible with single photon emission computed tomography (SPECT) 5. ![]() Recent successes in clinical trials with therapeutic isotope lead-212 ( 212Pb)-labeled radiopharmaceuticals is sparking significant interest in the potential of the element-equivalent 203Pb/ 212Pb theranostic pair as a means to develop image-guided, personalized cancer treatment plans for patients 4. The vector selectively seeks out and binds to unique cell biomarkers on cancer cells to directly and selectively deliver a radioactive payload, compatible with either imaging techniques or therapy dependent on the type of radioactive decay the radiometal undergoes, to cancer cells 2, 3. Bifunctional-chelator (BFC)-based radiopharmaceuticals for theranostics are composed of a radioactive metal coordinated to a bifunctional chelator attached, via a linker, to a biological targeting vector 2, 3. Overall, the goal of theranostics is to identify the most compatible treatment option for patients to improve clinical outcome 1. Within the field of nuclear medicine, theranostic radiopharmaceuticals (TRPs), where theranostic refers to the combination of a therapeutic and diagnostic agent, enable diagnostic imaging and therapy to be conducted simultaneously, or sequentially, to allow for the development of image-guided, personalized cancer treatment plans 1. 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 -cryptand. We implemented a novel, two-column purification method that employs selective Tl precipitation ( 203Pb only) alongside extraction and anion exchange chromatography to elute high specific activity and chemical purity 203/212Pb in a minimal volume of dilute acid, without the need for evaporation. In this study, improvements to 203Pb production were accomplished by manufacturing electroplated, silver-backed thallium (Tl) targets to improve target thermal stability, which allow for higher currents during irradiation. Together, 203Pb and 212Pb form an element-equivalent theranostic pair that potentiate image-guided, personalized cancer treatment, using 203Pb as a single-photon emission computed tomography (SPECT) source, and 212Pb for targeted alpha therapy. TRIUMF is one of the only laboratories in the world able to produce both lead-203 ( 203Pb, t 1/2 = 51.9 h) and 212Pb (t 1/2 = 10.6 h) onsite via its 13 and 500 MeV cyclotrons, respectively. ![]()
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