Assessment of Regional Lung Function Post-Pulmonary Embolism Using Ventilation/Perfusion PET/CT with Galligas and 68Ga-MAA

The primary objective of this study is to assess the impact of pulmonary rehabilitation (**PR**) on regional perfusion lung function using lung ventilation/perfusion (**V/Q**) PET/CT imaging in patients with pulmonary embolism. This evaluation is clinically relevant as it aims to enhance the understanding of how PR can improve lung function and potentially guide therapeutic strategies for individuals affected by pulmonary embolism.

Secondary objectives include:

• Assessing the correlation between regional lung function impairment, as evaluated by V/Q PET/CT imaging, and global lung function parameters.
• Evaluating the correlation between regional lung function impairment and quality of life.
• Comparing the pulmonary vascular obstruction index measured with conventional V/Q scan and V/Q PET/CT imaging.

The clinical trial focuses on individuals diagnosed with **pulmonary embolism**. The study population includes both male and female participants aged 18 years and older. Participants are required to have been treated with anticoagulation therapy for a period ranging from 3 to 8 months following an acute symptomatic pulmonary embolism, as per ESC and ACCP guidelines. The trial does not involve a vulnerable population. Participants must have a PembQol score of at least 10%, with specific subgroup scores for dyspnea and impact on daily life also meeting or exceeding 10%. An abnormal conventional V/Q scan at V1 is necessary for inclusion. The sponsor has not provided information regarding the total number of participants. The selection process ensures that participants have given consent to partake in the EOLE study. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the impact of pulmonary rehabilitation on regional perfusion lung function using ventilation/perfusion PET/CT imaging in patients with **pulmonary embolism**. This study employs a randomized, double-blind, controlled trial design to ensure the reliability and validity of the results. The trial is expected to span approximately 30 months, with an estimated recruitment start date of June 22, 2023, and an anticipated end date of December 22, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥ 18 years), prior treatment with anticoagulation for acute symptomatic pulmonary embolism, and specific quality of life scores. Following randomization, participants will attend follow-up visits to monitor their progress and assess primary and secondary endpoints, including the pulmonary vascular obstruction index and various global lung function parameters. The end-of-study visit will conclude the trial, where final assessments will be conducted.

The expected length of participant involvement is up to 8 months, depending on individual treatment responses and adherence to the study protocol. Conditions that may lead to early termination from the study include withdrawal of consent, adverse events, or non-compliance with study procedures. The trial aims to provide valuable insights into the effectiveness of pulmonary rehabilitation in improving lung function and quality of life in patients recovering from pulmonary embolism.

The clinical trial involves the use of two experimental medications for the assessment of regional lung function following pulmonary embolism. The first experimental medication is **Pulmocis**, a 2 mg kit for the preparation of a radiopharmaceutical suspension for injection. The active substance in Pulmocis is **human albumin as macroaggregates**, which is a structurally diverse substance derived from blood. The pharmaceutical form is a suspension for injection, and the administration route is via injection. The maximum daily dose is 185 MBq, with a total maximum dose of 370 MBq over a treatment period of up to 2 days. The product is manufactured by CIS BIO INTERNATIONAL and is not a pediatric formulation.

The second experimental medication is **PULMOTEC**, a graphite crucible for the preparation of Technegas for inhalation. The active substance is **graphite**, classified as a polymer. The pharmaceutical form is an inhalation powder, and the administration route is via inhalation. Similar to Pulmocis, the maximum daily dose is 185 MBq, with a total maximum dose of 370 MBq over a treatment period of up to 2 days. This product is manufactured by CYCLOMEDICA IRELAND LIMITED and is also not a pediatric formulation.

Both medications are used in the context of a clinical trial aimed at evaluating the impact of pulmonary rehabilitation on regional perfusion lung function using ventilation/perfusion PET/CT imaging. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed treatment regimen.

The efficacy of the clinical trial titled "Ventilation/Perfusion PET/CT with Galligas and 68Ga-MAA for regional lung function assessment after pulmonary embolism" will be assessed using both primary and secondary endpoints. The primary endpoint is the **Pulmonary Vascular Obstruction Index (PVOI)**, which is expressed as a percentage of whole lung volume and measured through V/Q PET/CT imaging. This index provides a quantitative assessment of the degree of vascular obstruction in the lungs.

Secondary endpoints include a range of parameters to evaluate regional lung function and overall respiratory health. These include the pulmonary ventilation impairment index and global lung function parameters such as dyspnea scores (MDP, Borg, and MMRC), respiratory functional tests (FVC, FEV, FVC-FEV, and TLco), and cardio-pulmonary exercise tests. Additionally, the trial will assess endurance through a cycloergometer test and a 6-minute walk test (6MWT). Quality of life will be evaluated using the PEmb-QoL score. These assessments will be conducted at various timepoints throughout the trial to monitor changes in lung function and patient well-being.