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

Abstract

Abstract 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.

Keywords

• 212Pb
• TOC
• Automation
• GMP-compliant
• Neuroendocrine tumour
• Somatostatin receptor