Changing regulatory requirements requiring changes in study design. Participants were not enrolled

Device:

EDDIS-IDDS (Enhanced Digital Dose Inhalation Delivery System) - a portable, breath-actuated, digitally monitored system for precision delivery of inhaled agents with automated recording of inspiratory volume, flow, duration, and breath-hold parameters.

Drug:

99mTc-DTPA (technetium-99m diethylenetriaminepentaacetic acid) - administered in aqueous solution (0.9% NaCl), radiolabeled for gamma scintigraphic imaging.

Total dose: 500-800 µCi in 2 ml solution.

Administration:

Single-dose inhalation under supervision in a clinical setting.

This Phase 1, single-center, open-label clinical study is designed to evaluate the safety, pharmacokinetics, inhalation dynamics, segmental lung deposition, and digital monitoring capabilities of the breath-actuated EDDIS-IDDS (Enhanced Digital Dose Inhalation Delivery System) when used to deliver a radiolabeled aqueous formulation containing 99mTc-DTPA and a microdose of perfluorocarbon emulsion.

The investigational aerosol is administered via a digitally controlled inhalation system that automatically triggers delivery based on the patient's inspiratory effort. The system continuously records real-time parameters including tidal volume, inspiratory flow rate, inhalation duration, and breath-hold time. These data are securely transmitted and stored for analysis, enabling high-resolution correlation between inhalation patterns and lung deposition outcomes.

The radiolabel (99mTc-DTPA) is confined to the aqueous phase of the aerosol. The perfluorocarbon emulsion is included to simulate the aerodynamic behavior of complex liquid formulations and to evaluate their interaction with the lung architecture under controlled inhalation conditions. Radiolabeling is not applied to the perfluorocarbon phase, ensuring imaging specificity and avoiding nonspecific signal interference.

Imaging will be performed using planar gamma scintigraphy at 0, 15, and 30 minutes post-inhalation. Anterior and posterior projections will be acquired to allow quantitative segmental lung analysis. Measurements will include total deposition, central vs. peripheral distribution, and temporal sedimentation characteristics.

In parallel, blood samples will be collected at 1, 2, and 4 hours post-dose to determine systemic pharmacokinetics of the radiolabeled tracer. Urine samples collected at 4 hours will be used to calculate cumulative renal excretion. Adverse events, vital signs, and laboratory parameters will be monitored for 24 hours post-inhalation to assess tolerability and safety.

This study aims to establish a validated digital platform for inhaled delivery research and serve as a reference model for future studies involving targeted pulmonary therapeutics and diagnostic aerosols.

Inclusion Criteria:

• Age between 18 and 45 years
• Healthy adults with no clinically significant medical history
• Normal spirometry (FEV1 ≥ 80% predicted)
• Body Mass Index (BMI) between 18.5 and 29.9 kg/m²
• No prior exposure to radiopharmaceuticals in the past 12 months
• Able and willing to comply with study procedures and provide written informed consent
• Current or past use of tobacco products or electronic nicotine delivery systems (e.g., e-cigarettes) is not an exclusion criterion

Exclusion Criteria:

• History of asthma, COPD, or other chronic respiratory conditions
• History of lung surgery, pulmonary embolism, or interstitial lung disease
• Any ongoing respiratory infection or fever ≥ 38.0°C at screening or study day
• Uncontrolled or progressive arterial hypertension
• Known cardiovascular disease (e.g., arrhythmia, ischemic heart disease, heart failure)
• Presence of blood in saliva, hemoptysis, or any known pulmonary bleeding
• Diagnosed pulmonary emphysema
• Known coagulation disorders or use of anticoagulant therapy
• History of hypersensitivity to perfluorocarbons, DTPA, or radiopharmaceutical agents
• Prior exposure to radiopharmaceuticals within the last 12 months
• Participation in another clinical trial within the last 60 days
• Pregnancy or breastfeeding
• Use of any investigational or prescription drug within 30 days prior to study drug administration
• Any condition which, in the opinion of the investigator, would pose a health risk or interfere with study interpretation

This is a non-therapeutic, device validation study with radiolabeled imaging in healthy volunteers. No individual-level participant data will be shared. Aggregated, de-identified study results may be published in scientific journals or presented at scientific meetings.

No masking will be applied. Participants, investigators, and outcomes assessors will be aware of the intervention, as this is a non-therapeutic, Phase 1 imaging and device validation study