Lung ventilation/perfusion (V/Q) positron emission tomography-computed tomography (PET/CT) is a promising imaging modality for regional lung function assessment. The same carrier molecules as a conventional V/Q scan (i.e., carbon nanoparticles for ventilation and macro aggregated albumin particles for perfusion) are used, but they are labeled with gallium-68 (⁶⁸Ga) instead of technetium-99m (^99mTc). For both radiopharmaceuticals, various production processes have been proposed. This article discusses the challenges associated with the transition from ^99mTc- to ⁶⁸Ga-labelled radiopharmaceuticals. The various production and optimization processes for both radiopharmaceuticals are reviewed and discussed for optimal clinical use.

Invented and first approved for clinical use in Australia 36 years ago, Technegas is the technology that enabled ventilation scintigraphy with ^99mTc-labeled carbon nanoparticles (^99mTc-CNP). The US Food and Drug Administration (FDA) has considered this technology for more than 30 years but only now is getting close to approving it. Meanwhile, more than 4.4 million patients benefited from this technology in 64 countries worldwide. The primary application of ^99mTc-CNP ventilation imaging is the diagnostic evaluation for suspicion of pulmonary embolism using ventilation-perfusion quotient (V/Q) imaging. Because of ^99mTc-CNP's long pulmonary residence, tomographic imaging emerged as the preferred V/Q methodology. The FDA-approved ventilation imaging agents are primarily suitable for planar imaging, which is less sensitive. After the FDA approval of Technegas, the US practice will likely shift to tomographic V/Q. The ^99mTc-CNP use is of particular interest in the COVID-19 pandemic because it offers an option of a dry radioaerosol that takes approximately only 3 to 5 tidal breaths, allowing the shortest exposure to and contact with possibly infected patients. Indeed, countries where ^99mTc-CNP was approved for clinical use continued using it throughout the COVID-19 pandemic without known negative viral transmission consequences. Conversely, the ventilation imaging was halted in most US facilities from the beginning of the pandemic. This review is intended to familiarize the US clinical nuclear medicine community with the basic science of ^99mTc-CNP ventilation imaging and its clinical applications, including common artifacts and interpretation criteria for tomographic V/Q imaging for pulmonary embolism.

Background: Gallium-68 lung perfusion PET/CT is an emerging imaging modality for the assessment of regional lung function, especially to optimise radiotherapy (RT) planning. A key step of lung functional avoidance RT is the delineation of lung functional volumes (LFVs) to be integrated into radiation plans. However, there is currently no consistent and reproducible delineation method for LFVs. The aim of this study was to develop and evaluate an automated delineation threshold method based on total lung function for LFVs delineation with Gallium-68 MAA lung PET/CT imaging. Material and Method: Patients prospectively enrolled in the PEGASUS trial—a pilot study assessing the feasibility of lung functional avoidance using perfusion PET/CT imaging for lung stereotactic body radiotherapy (SBRT) of primary or secondary lesion—were analysed. Patients underwent lung perfusion MAA-68Ga PET/CT imaging and pulmonary function tests (PFTs) as part of pre-treatment evaluation. LFVs were delineated using two methods: the commonly used relative to the maximal pixel value threshold method (pmax threshold method, X%pmax volumes) and a new approach based on a relative to whole lung function threshold method (WLF threshold method, FVX% volumes) using a dedicated iterative algorithm. For both methods, LFVs were expressed in terms of % of the anatomical lung volume (AV) and of % of the total lung activity. Functional volumes were compared for patients with normal PFTs and pre-existing airway disease. Results: 60 patients were analysed. Among the 48 patients who had PFTs, 31 (65%) had pre-existing lung disease. The pmax and WLF threshold methods clearly provided different functional volumes with a wide range of relative lung function for a given pmax volume, and conversely, a wide range of corresponding pmax values for a given WLF volume. The WLF threshold method provided more reliable and consistent volumes with much lower dispersion of LFVs as compared to the pmax method, especially in patients with normal PFTs. Conclusions: We developed a relative to whole lung function threshold segmentation method to delineate lung functional volumes on perfusion PET/CT imaging. The automated algorithm allows for reproducible contouring. This new approach, relatively unaffected by the presence of hot spots, provides reliable and consistent functional volumes, and is clinically meaningful for clinicians.

The aim of this study was to assess the feasibility of sparing functional lung areas by integration of pulmonary functional mapping guided by ⁶⁸Ga-perfusion PET/CT imaging in lung SBRT planification. Sixty patients that planned to receive SBRT for primary or secondary lung tumors were prospectively enrolled. Lung functional volumes were defined as the minimal volume containing 50% (FV50%), 70% (FV70%) and 90% (FV90%) of the total activity within the anatomical volume. All patients had a treatment planning carried out in 2 stages: an anatomical planning blinded to the PET results and then a functional planning respecting the standard constraints but also incorporating “lung functional volume” constraints. The mean lung dose (MLD) in functional volumes and the percentage of lung volumes receiving xGy (VxGy) within the lung functional volumes using both plans were calculated and compared. SBRT planning optimized to spare lung functional regions led to a significant reduction (p < 0.0001) of the MLD and V5 to V20 Gy in all functional volumes. Median relative difference of the MLD in the FV50%, FV70% and FV90% was −8.0% (−43.0 to 1.2%), −7.1% (−34.3 to 1.2%) and −5.7% (−22.3 to 4.4%), respectively. Median relative differences for VxGy ranged from −12.5% to −9.2% in the FV50%, −11.3% to −7.2% in the FV70% and −8.0% to −5.3% in the FV90%. This study shows the feasibility of significantly decreasing the doses delivered to the lung functional volumes using ⁶⁸Ga-perfusion PET/CT while still respecting target volume coverage and doses to other organs at risk.

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 (>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.