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

Background

Recently, radiotheranostics comprising the true matched radionuclide pair ^203/212Pb could serve as real dosimetric planning utility using ²⁰³Pb-radiolabelled pharmaceuticals before therapy with ²¹²Pb-radiolabelled counterparts. ²¹²Pb might act as the missing radionuclide therapy between standard β^– therapies (e.g. with ¹⁷⁷Lu or ⁹⁰Y), in some cases leading to β^– resistance and highly cytotoxic α therapies (e.g. with ²²⁵Ac) leading in some cases to renal insufficiency or even renal failure, due to the daughter nuclide ²¹³Bi, which accumulates in > 90% within the kidneys during ²²⁵Ac therapy. ²¹²Pb converts to ²¹²Bi 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. ²⁰⁸Tl), 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 [²¹²Pb]Pb-PSC-PEG₂-TOC ([²¹²Pb]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 ²²⁴Ra/²¹²Pb-generator, radiolabelling, C18 purification and sterile filtration performed automatically within one hour to access [²¹²Pb]Pb-VMT-α-NET for patient application. [²¹²Pb]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 [²¹²Pb]Pb-VMT-α-NET in high purity for patient application. By changing the precursor this process could easily be adapted to other ²¹²Pb-radiopharmaceuticals.