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.