U01FD007987

A prospective study to support validation of lung deposition models with nuclear medicine imaging methods - project summary.

In this project, we propose to develop and execute protocols for a nuclear imaging deposition study using either single-photon emission computed tomography (SPECT) or, preferably, positron emission tomography (PET), with the goal of supporting validation of in-silico models of deposition.

These protocols, developed in collaboration with the FDA, will be optimized to 1) collect data which may be used as input parameters for the models which use this data for validation purposes and 2) leverage recent advances in SPECT and PET technology to achieve images with significantly higher spatial and temporal resolution than was previously possible.

Building on approaches developed primarily by researchers Fleming, Montesantos, and Greenblatt, we will develop methods to derive more accurate estimations of branch-level deposition from the resulting images by 1) leveraging our experience in quantitative CT segmentation of lung structure, 2) making use of improvements in image resolution to optimize radiotracer activity localization within airways as small as the 4th generation, 3) localizing radiotracer activity within anatomic compartments of the lung as small as the segmental level, and 4) more accurately reflecting disease-specific variations in airway morphology which violate key assumptions of the work of Fleming and Montesantos.

These protocols will be developed and executed in collaboration with personnel from the nuclear medicine and radiology and pharmacology faculty at Erasmus Medical Center as subawardees. These researchers will be primarily responsible for developing, validating, and implementing a process to produce a radiolabeled formulation of one orally inhaled drug product (OIDP) which is fit-for-use, as well as appropriate SPECT or PET protocols optimized for the needs of the overall project.

Healthy volunteers and subjects with asthma or COPD will be recruited from a single center located in Kontich, Belgium. By recruiting subjects with asthma and COPD, we hope to develop methods which can account for clinically significant differences in ventilation and deposition which are not accounted for in previous work, specifically emphysema and gas trapping.

The resulting data, including 1) standardized protocols and procedures, 2) images acquired, 3) methods and code, and 4) results of analysis will be made available to the FDA to disseminate publicly 18 months following completion of the study, to meet the objective of providing data to facilitate in-silico model validation.

Fluidda

NOT APPLICABLE

93.103 - Food and Drug Administration Research

FDA Office of Acquisition and Grant Services (OAGS) [HHS - FDA]

Center for Drug Evaluation and Research (CDER) [HHS - FDA]

New York, New York 100173337 United States

Single Zip Code

In Vivo Regional Deposition Measurements for Supporting Model Validation (U01) Clinical Trial Required (RFA-FD-23-014)

Amendment Since initial award the End Date has been extended from 08/31/26 to 08/31/27 and the total obligations have increased 199% from $332,947 to $996,903.