Validation of a radiosynthesis method and a novel quality control system for [68 Ga]Ga-MAA: is TLC enough to assess radiopharmaceutical quality?

• Main Authors: Silvia Migliari (Author), Stefano Bruno (Author), Annalisa Bianchera (Author), Ilaria De Nardis (Author), Antonio Scarano (Author), Monica Lusardi (Author), Anna Gaiani (Author), Alessandra Guercio (Author), Maura Scarlattei (Author), Giorgio Baldari (Author), Ruggero Bettini (Author), Livia Ruffini (Author)
• Format: Book
• Published: SpringerOpen, 2024-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1186/s41181-024-00302-x; 2365-421X
• Keywords: [68 Ga]Ga-macroaggregated human serum albumin; Radiopharmaceuticals; High pressure liquid chromatography; SDS-PAGE; Morphological structure and size distribution; Lung perfusion imaging; Medical physics. Medical radiology. Nuclear medicine; R895-920; Therapeutics. Pharmacology; RM1-950
• Source: EJNMMI Radiopharmacy and Chemistry, Vol 9, Iss 1, Pp 1-21 (2024)

Abstract Background Technetium-99 m-labelled macroaggregated human serum albumin ([99mTc]Tc-MAA) is commonly used for lung perfusion scintigraphy. The European Pharmacopoeia (Eu.Ph.) specifies thin-layer chromatography (TLC) as the only method to assess its radiochemical purity (RCP). Similarly, TLC is the sole method reported in the literature to evaluate the RCP of Gallium-68-labelled MAA [68 Ga]Ga-MAA, recently introduced for lung perfusion PET/CT imaging. Since [68 Ga]Ga-MAA is prepared from commercial kits originally designed for the preparation of [99mTc]Tc-MAA, it is essential to optimize and validate the preparation methods for [68 Ga]Ga-MAA. Results We tested a novel, simplified method for the preparation of [68 Ga]Ga-MAA that does not require organic solvents, prewash or final purification steps to remove radioactive impurities. We assessed the final product using radio-TLC, radio-UV-HPLC, and radio SDS-PAGE. Overall, our quality control (QC) method successfully detected [68 Ga]Ga-MAA along with all potential impurities, including free Ga-68, [68 Ga]Ga-HSA, unlabeled HSA, which may occur during labelling process and HEPES residual, a non-toxic but non-human-approved contaminant, used as buffer solution. We then applied our QC system to [68 Ga]Ga-MAA prepared under different conditions (25°-40°-75°-95 °C), thus defining the optimal temperature for labelling. Scanning Electron Microscopy (SEM) analysis of the products obtained through our novel method confirmed that most [68 Ga]Ga-MAA particles preserved the morphological structure and size distribution of unlabeled MAA, with a particle diameter range of 25-50 μm, assuring diagnostic efficacy. Conclusions We optimized a novel method to prepare [68 Ga]Ga-MAA through a QC system capable of monitoring all impurities of the final products.