Issues with the European Pharmacopoeia Quality Control Method for ^99mTc-Labelled Macroaggregated Albumin

Area of Science:

• Nuclear medicine
• Radiopharmaceutical quality control
• Medical imaging

Background:

• Technetium-99m macroaggregated albumin ([99mTc]Tc-MAA) is crucial for lung perfusion scintigraphy.
• A new MAA batch exhibited abnormal liver and spleen uptake, despite meeting European Pharmacopoeia (Ph. Eur.) standards.
• This discrepancy highlighted potential issues with current MAA quality control methods.

Purpose of the Study:

• To investigate the cause of unexpected in vivo biodistribution of [99mTc]Tc-MAA.
• To develop and present a simple, effective method for assessing MAA particle size.
• To advocate for revisions to the Ph. Eur. quality control for MAA.

Main Methods:

• Comparative analysis of a problematic MAA batch with a standard batch from another manufacturer.
• Particle size analysis of different MAA batches.
• Correlation of particle size data with observed in vivo biodistribution in lung perfusion scintigraphy.

Main Results:

• The problematic MAA batch contained a significantly higher number of small particles compared to the standard batch.
• The presence of smaller particles correlated with the observed unwanted uptake in the liver and spleen.
• The proposed simple particle size test effectively predicted the in vivo performance of [99mTc]Tc-MAA.

Conclusions:

• The European Pharmacopoeia's current MAA quality control method may not adequately detect particle size variations that impact in vivo performance.
• A simple particle size test is a valuable tool for predicting the clinical efficacy and safety of [99mTc]Tc-MAA.
• MAA manufacturers should consider adopting this improved quality control method to ensure product consistency and patient safety.