Fully Automated 68Ga-Labeling and Purification of Macroaggregated Albumin Particles for Lung Perfusion PET Imaging

Frédérique Blanc-Béguin,Pierre-Yves Salaün,Pierre-Yves Le Roux,Philippe Robin,Peter Eu,Virginie Cogulet,Julien Masset,Simon Hennebicq,Valérie Guilloux,Raphaël Tripier,Corentin Warnier,Charles Vriamont

doi:10.3389/fnume.2021.778191

Abstract

Lung PET/CT is a promising imaging modality for regional lung function assessment. Our aim was to develop and validate a fast, simple, and fully automated GMP compliant [68Ga]Ga-MAA labeling procedure, using a commercially available [99mTc]Tc-MAA kit, a direct gallium-68 eluate and including a purification of the [68Ga]Ga-MAA.Method: The synthesis parameters (pH, heating temperature) were manually determined. Automated 68Ga-labeling of MAA was then developed on a miniAIO (Trasis®, Ans, Belgium) module. An innovative automated process was developed for the purification. The process was then optimized and adapted to automate both the [68Ga]Ga-MAA synthesis and the isolation of gallium-68 eluate required for the pulmonary ventilation PET/CT.Results: The 15-min process demonstrated high reliability and reproducibility, with high synthesis yield (&gt;95 %). Mean [68Ga]Ga-MAA radiochemical purity was 99 % ± 0.6 %. The 68Ga-labeled MAA particles size and morphology remained unchanged.Conclusion: A fast, user friendly, and fully automated process to produce GMP [68Ga]Ga-MAA for clinical use was developed. This automated process combining the advantages of using a non-modified MAA commercial kit, a gallium-68 eluate without pre-purification and an efficient final purification of the [68Ga]Ga-MAA may facilitate the implementation of lung PET/CT imaging in nuclear medicine departments.

Highlights

Ventilation-perfusion (V/Q) PET/CT (Positron Emission Tomography/Computed Tomography) is a promising imaging modality for regional lung function assessment
We developed a fully automated process to produce Good Manufacturing Practices (GMP) [68Ga]Ga-MAA for clinical use, using a non-modified MAA commercial kit and a direct gallium-68 eluate
At pH from 4.3 to 5.3, a heating temperature of 80◦C or more altered the MAA quality. These data are in line with a study from Amor-Coaraza et al, which showed that a heating stage of 15 min at a temperature superior to 75◦C resulted in a higher concentration of small particles in the reaction mixture, which could be explained by the rupture of large macroaggregates [15, 19]

Summary

Introduction

Ventilation-perfusion (V/Q) PET/CT (Positron Emission Tomography/Computed Tomography) is a promising imaging modality for regional lung function assessment. The same carrier molecules as conventional V/Q scan are used (i.e., carbon nanoparticles for ventilation and macro aggregated albumin (MAA) for perfusion), but they are labeled with gallium-68 instead of technetium-99m [1]. Thereby, V/Q PET/CT and V/Q SPECT/CT imaging assesses similar physiological processes,. [68Ga]Ga-MAA Synthesis: Fully Automated Process but with the technical advantages of PET over conventional SPECT imaging, including higher sensitivity, spatial and temporal resolution, and speed of acquisition [2, 3]. The transition from SPECT to PET technology showed promising results in a variety of pulmonary diseases, including pulmonary embolism diagnosis [4, 5], assessment of pulmonary reserve in lung cancer patients before surgery [6], radiotherapy planning to maximize dose to the tumor while minimizing the dose to the surrounding lungs [7–10], or surgical evaluation of patients undergoing lung volume reduction surgery [11]. The use of gallium-68 could be a suitable alternative to prevent production delays due to 99Mo/99mTc generator shortage [12]

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