Challenges in assessing regional distribution of inhaled drug in the human lungs.

INTRODUCTION: Both the total amount of drug deposited in the lungs (whole lung deposition) and the amount deposited in different lung regions (regional lung deposition) are potentially important factors that determine the safety and efficacy of inhaled drugs. Radionuclide imaging is well established for quantifying the whole lung deposition of inhaled drugs, but the assessment of regional lung deposition is less straightforward, because of the complex nature of the lung anatomy. AREAS COVERED: This review describes the challenges and problems associated with quantifying regional lung deposition by the two-dimensional (2D) radionuclide imaging method of gamma scintigraphy, and by the three-dimensional (3D) radionuclide imaging methods of single-photon-emission computed tomography (SPECT) and positron-emission tomography (PET). The advantages and disadvantages of each method for assessing regional lung deposition are discussed. EXPERT OPINION: Owing to its 2D nature, gamma scintigraphy provides limited information about regional lung deposition. SPECT provides regional lung deposition data in three dimensions, but usually involves a (99m)Tc radiolabel. PET enables the regional lung deposition of radiolabeled drug molecules to be quantified in three dimensions, but poses the greatest logistical and technical difficulties. Despite their more challenging nature, 3D imaging methods should be considered as an alternative to gamma scintigraphy whenever the determination of regional lung deposition of pharmaceutical aerosols is a major study objective.