A pharmacokinetic approach to the evaluation of aerosol solutes for lung permeability studies
The distribution and clearance of inhaled radioactive aerosols prepared from five Tc-99m labelled derivatives of HIDA, Tc-99m DTPA and Tc-99m 04- were evaluated in Beagle dogs. The investigation was designed to develop new aerosol solutes and to obtain information on molecular transport across the alveolar capillary membrane by evaluating molecular structure versus biological activity relationships. Aerosols with an aerodynamic mean diameter of .48 microns (sigmag=1.50), produced in a jet nebulizer, were administered to anesthetized dogs through an endotrachial tube. Aerosols were evaluated twice in each of five dogs for three HIDA derivatives, pertechnetate, and DTPA. Two other HIDA derivatives were evaluated twice in one animal. Sixty min. quantitative gamma camera studies were obtained. ROI processing and functional mapping of images showed distribution and clearance of identically sized aerosols to have a strong dependance on chemical properties. Dimethyl HIDA, trimethylbromo HIDA, and DISIDA with capacity factors (k') of -0.24, 0.63, and 0.65 respectively gave mean lung clearance t1/2 times of 76.6, 206.7, and 97.3 min. 4-bromo HIDA and 3,5-dichloro HIDA were administered to one animal; t1/2 times were 80.0 and 330 min. Two hydro-philic compounds, Tc-99m DTPA and Tc-99m 04-, were examined; t1/2 times were 49.6 min. and 21.2 min. respectively. A trend is seen where t1/2 values increase with lipophilicity; this suggests that structure activity relationships could be built on lipophilicity. These studies support the contention that molecular transport in the lung is an intercellular mechanism.
- Research Organization:
- Univ. of Rochester School of Medicine and Dentistry, Rochester, NY
- OSTI ID:
- 6859254
- Report Number(s):
- CONF-840619-; TRN: 87-019058
- Journal Information:
- J. Nucl. Med.; (United States), Vol. 25:5; Conference: 31. annual meeting of the Society of Nuclear Medicine, Los Angeles, CA, USA, 5 Jun 1984
- Country of Publication:
- United States
- Language:
- English
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62 RADIOLOGY AND NUCLEAR MEDICINE
CHEST
SCINTISCANNING
LUNGS
DYNAMIC FUNCTION STUDIES
INJURIES
AEROSOLS
BEAGLES
CELL MEMBRANES
DTPA
GAMMA CAMERAS
INHALATION
PERMEABILITY
RADIATION DOSES
RADIONUCLIDE KINETICS
RADIOSENSITIVITY
TISSUE DISTRIBUTION
AMINO ACIDS
ANIMALS
BODY
BODY AREAS
CAMERAS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHELATING AGENTS
COLLOIDS
COUNTING TECHNIQUES
DIAGNOSTIC TECHNIQUES
DISPERSIONS
DISTRIBUTION
DOGS
DOSES
DRUGS
INTAKE
MAMMALS
MEMBRANES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
RADIOISOTOPE SCANNING
RADIOPROTECTIVE SUBSTANCES
RESPIRATORY SYSTEM
SOLS
VERTEBRATES
551001* - Physiological Systems- Tracer Techniques
550601 - Medicine- Unsealed Radionuclides in Diagnostics