Optimized production, purification, and radiolabeling of the 203Pb/212Pb theranostic pair for nuclear medicine

Abstract

TRIUMF is one of the only laboratories in the world able to produce both lead-203 (203Pb, t1/2 = 51.9 h) and 212Pb (t1/2 = 10.6 h) onsite via its 13 and 500 MeV cyclotrons, respectively. 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. 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. 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. 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.

Exploring the use of rigid 18-membered macrocycles with amide pendant arms for Pb(ii)-based radiopharmaceuticals

“…[ 203 Pb]Pb( ii ) was produced and purified according to the procedure reported by McNeil et al , without any modifications. 80 Concentration dependent radiolabelling for all four chelators and DOTAM, the gold-standard for radiolabelling with lead( ii ) isotopes, was performed in NH 4 OAc buffer (0.1 M, pH 7) at five different chelator concentrations (10 −4 , 10 −5 , 10 −6 , 10 −7 and 10 −8 M). The reactions were followed at two time points (30 and 60 minutes) and two temperatures (room temperature: ∼25 °C, and 80 °C).…”

Incorporation of Carboxylate Pendant Arms into 18‐Membered Macrocycles: Effects on [nat/203Pb]Pb(II) Complexation

“…Radiolabeling experiments were conducted to evaluate the behavior of the chelators towards [ 203 Pb]Pb(II). The radioisotope was produced on a 13 MeV cyclotron and purified following a previously reported procedure, without any modifications [52] . First, concentration dependent radiolabeling of the two chelators, and DOTAM as a control, was carried out at ambient temperature and 80 °C with five chelator concentrations (10 −4 , 10 −5 , 10 −6 , 10 −7 and 10 −8 M).…”

Separation of lead-212 from natural thorium solution utilizing novel sulfonamide dibenzo-18-crown-6

“…To maximize the extraction of 212 Pb from the solution, the DSADB18C6 concentration was adjusted to 100 mmol L −1 . The radiation activity (A) and radiochemical recovery (R) of 212 Pb can be defined by eqn ( 4) and (5).…”

“…[1][2][3] However, accelerator and reactor production stand as the primary means of obtaining numerous medical isotopes. 4,5 The necessity for specialized facilities and precise accelerator beam control significantly inflates the cost. 6 Fortunately, 212 Pb can be extracted directly from natural thorium, which is abundant in the mining waste of rare-earth, uranium, etc.…”

“…This approach proved exceptional suitability for separating 212 Pb, especially under highly acidic conditions, from thorium nitrate solutions. 5,[30][31][32] Despite the superior complexation capabilities of crown ether with Pb(II), crown ethers have not yet taken a favourable position in the 212 Pb extraction process due to the challenges of the water solubility of 18C6, the relatively high production cost of DtBuDC18C6, and the weak extractability of DB18C6. 33 Based on the insights mentioned above, we chose to enhance the properties DB18C6 molecule by introducing sulfonic acid groups and grafting hydrophobic alkyl chains.…”