Lead-it-EAZY! GMP-compliant production of [Pb]Pb-PSC-PEG-TOC.

Background: Recently, radiotheranostics comprising the true matched radionuclide pair Pb could serve as real dosimetric planning utility using Pb-radiolabelled pharmaceuticals before therapy with Pb-radiolabelled counterparts. Pb might act as the missing radionuclide therapy between standard β therapies (e.g. with Lu or Y), in some cases leading to β resistance and highly cytotoxic α therapies (e.g. with Ac) leading in some cases to renal insufficiency or even renal failure, due to the daughter nuclide Bi, which accumulates in > 90% within the kidneys during Ac therapy. Pb converts to 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. 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 [Pb]Pb-PSC-PEG-TOC ([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 Ra/Pb-generator, radiolabelling, C18 purification and sterile filtration performed automatically within one hour to access [Pb]Pb-VMT-α-NET for patient application. [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 [Pb]Pb-VMT-α-NET in high purity for patient application. By changing the precursor this process could easily be adapted to other Pb-radiopharmaceuticals.