High-yield cyclotron production of 203Pb using a sealed 205Tl solid target

203Pb (t1/2 = 51.9 h, 279 keV (81 %)) is a diagnostic SPECT imaging radionuclide ideally suited for theranostic applications in combination with 212Pb for targeted alpha particle therapy. Our objectives were to develop a high-yield solid target 203Pb cyclotron production route using isotopically enriched 205Tl target material and the 205Tl(p,3n)203Pb reaction as an alternative to lower energy production via the 203Tl(p,n)203Pb reaction.250 mg 205Tl metal (99.9 % isotopic enrichment) was pressed using a hardened stainless steel die. Aluminum target discs were machined with a central depression and annulus groove. The flattened 205Tl pellet was placed into the central depression of the Al disc and a circle of indium wire was laid in the machined annulus surrounding the pellet. An aluminum foil cover was then pressed onto the target disc to create an airtight bond. Targets were irradiated at 23.3 MeV for up to 516 min on a TR-24 cyclotron at currents up to 60 μA to produce 203Pb via the 205Tl(p,3n)203Pb nuclear reaction. Following a cool-down period of >12 h, the target was removed and 205Tl dissolved in 4 M HNO3. A NEPTIS Mosaic-LC synthesis unit performed automated separation using Eichrom Pb resin, and 203Pb was eluted using 8 M HCl or 1 M NH4OAc. 205Tl was diverted to a vial for recovery in an electrolytic cell. 203Pb product radionuclidic purity was assessed by HPGe gamma spectroscopy, while elemental purity was assessed by ICP-OES. Radiolabeling and stability studies were performed with PSC, TCMC, and DOTA chelators, and 203Pb incorporation was verified by radio-TLC analysis.Cyclotron irradiations performed at 60 μA proton beam current and 23.3 MeV (205Tl incident energy) had a 203Pb saturated yield of 4658 ± 62 MBq/μA (n = 3). Automated NEPTIS separation took <4 h from the start of target dissolution to product elution, yielding >85 % decay-corrected [203Pb]PbCl2 with a radionuclidic purity of >99.9 %. Purified [203Pb]PbCl2 yields of up to 12 GBq 203Pb were attained (15.8 GBq at EOB). The [203Pb]PbCl2 and [203Pb]Pb(OAc)2 products contained no detectable radionuclidic impurities besides 201Pb (<0.1 %), and <0.4 ppm stable Pb. 205Tl metal was recovered with a 92 % batch yield. Aliquots of 100 μL [203Pb]Pb(OAc)2 were used for radiolabeling PSC-Bn-NCS, TCMC-NCS, and DOTA-NCS chelators at pH 4.5 and 22 °C for 30 min, with maximum respective molar activities of 461 ± 30 GBq/μmol, 195 ± 37 GBq/μmol, and 83 ± 12 GBq/μmol. PSC, TCMC, and DOTA chelators exhibited >99.9 % incorporation after a 120-hour incubation in human serum at 37 °C.Nuclear medicine centers with access to higher energy cyclotrons can produce large 203Pb activities sufficient for clinical applications, with a convenient separation technique producing highly pure [203Pb]PbCl2 or [203Pb]Pb(OAc)2 for direct radiolabeling. This represents an attractive route to produce 203Pb for diagnostic SPECT imaging alongside 212Pb targeted alpha particle therapy.Our high-yield 203Pb production technique significantly enhances 203Pb production capabilities to meet the growing preclinical and clinical demand for 203Pb radiopharmaceuticals alongside 212Pb target alpha particle therapy.