Journal article
Lead-it-EAZY! GMP-compliant production of [ 212 Pb]Pb-PSC-PEG 2 -TOC
EJNMMI radiopharmacy and chemistry, Vol.9(1), 81
11/27/2024
DOI: 10.1186/s41181-024-00305-8
PMCID: PMC11602913
PMID: 39604560
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.
Details
- Title: Subtitle
- Lead-it-EAZY! GMP-compliant production of [ 212 Pb]Pb-PSC-PEG 2 -TOC
- Creators
- Marc Pretze - University Hospital Carl Gustav CarusEnrico Michler - University Hospital Carl Gustav CarusDavid Kästner - University Hospital Carl Gustav CarusFalk Kunkel - Eckert & Ziegler (United States)Edwin A Sagastume - Perspective Therapeutics, Coralville, IA, 52241, USAMichael K Schultz - University of IowaJörg Kotzerke - University Hospital Carl Gustav Carus
- Resource Type
- Journal article
- Publication Details
- EJNMMI radiopharmacy and chemistry, Vol.9(1), 81
- DOI
- 10.1186/s41181-024-00305-8
- PMID
- 39604560
- PMCID
- PMC11602913
- NLM abbreviation
- EJNMMI Radiopharm Chem
- eISSN
- 2365-421X
- Publisher
- SPRINGERNATURE
- Grant note
- Technische Universitt Dresden (1019)
The authors want to thank Holger Hartmann for his excellent technical support in radiation safety evaluation for the personnel by handling the 224Ra/212Pb generator. The authors also acknowledge support of the Eckert&Ziegler GmbH in form of providing cassettes and the synthesis module.
- Language
- English
- Date published
- 11/27/2024
- Academic Unit
- Radiology; Radiation Oncology
- Record Identifier
- 9984752658902771
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