Lead-it-EAZY! GMP-compliant production of [212Pb]Pb-PSC-PEG2-TOC

Abstract Background Recently, radiotheranostics comprising the true matched radionuclide pair 203/212 Pb could serve as real dosimetric planning utility using 203 Pb-radiolabelled pharmaceuticals before therapy with 212 Pb-radiolabelled counterparts. 212 Pb might act as the missing radionuclide therapy between standard β – therapies (e.g. with 177 Lu or 90 Y), in some cases leading to β – resistance and highly cytotoxic α therapies (e.g. with 225 Ac) leading in some cases to renal insufficiency or even renal failure, due to the daughter nuclide 213 Bi, which accumulates in > 90% within the kidneys during 225 Ac therapy. 212 Pb converts to 212 Bi by β – -decay and the following pathway of decay bears in sum only one α decay, which certainly happens within the targeted tumour tissue. Following daughter nuclides (e.g. 208 Tl), which could distribute in organs at risk have only β − or γ decay, which is not as cytotoxic as α decay. Results By ingenious customization of the standard cassettes of the ML EAZY it was possible to adapt the manual radiosynthesis of [ 212 Pb]Pb-PSC-PEG 2 -TOC ([ 212 Pb]Pb-VMT-α-NET) to a GMP-compliant synthesis module. The whole process of production, namely conditioning of C18 cartridge for purification, elution of the 224 Ra/ 212 Pb-generator, radiolabelling, C18 purification and sterile filtration performed automatically within one hour to access [ 212 Pb]Pb-VMT-α-NET for patient application. [ 212 Pb]Pb-VMT-α-NET was radiolabelled with high radiochemical purity > 95% and high radiochemical yield > 95% with molar activity ~ 15.8 MBq/nmol. Conclusions The Lead-it-EAZY process performed stable and robust over ten radiosyntheses and yielded sterile [ 212 Pb]Pb-VMT-α-NET in high purity for patient application. By changing the precursor this process could easily be adapted to other 212 Pb-radiopharmaceuticals.