Christian Lackas

Regional particle size dependent deposition of inhaled aerosols in rats and mice

Context: The current data analysis tools in nuclear medicine have not been used to evaluate intra organ regional deposition patterns of pharmaceutical aerosols in preclinical species. Objective: This study evaluates aerosol deposition patterns as a function of particle size in rats and mice using novel image analysis techniques. Materials and Method: Mice and rats were exposed to radiolabeled polydisperse aerosols at 0.5, 1.0, 3.0, and 5.0 µm MMAD followed by SPECT/CT imaging for deposition analysis. Images were quantified for both macro deposition patterns and regional deposition analysis using the LRRI-developed Onion Model. Results: The deposition fraction in both rats and mice was shown to increase as the particle size decreased, with greater lung deposition in rats at all particle sizes. The Onion Model indicated that the smaller particle sizes resulted in increased peripheral deposition. Discussion: These data contrast the commonly used 10% deposition fraction for all aerosols between 1.0 and 5.0 µm and indicate that lung deposition fraction in this range does change with particle size. When compared to historical data, the 1.0, 3.0, and 5.0 µm particles result in similar lung deposition fractions; however, the 0.5 µm lung deposition fraction is markedly different. This is probably caused by the current aerosols that were polydisperse to reflect current pharmaceutical aerosols, while the historical data were generated with monodisperse aerosols. Conclusion: The deposition patterns of aerosols between 0.5 and 5.0 µm showed an increase in both overall and peripheral deposition as the particle size decreased. The Onion Model allows a more complex analysis of regional deposition in preclinical models.

Assessing Antibody Pharmacokinetics in Mice with In Vivo Imaging

Recent advances in small-animal molecular imaging instrumentation combined with well characterized antibody-labeling chemistry have enabled detailed in vivo measurements of antibody distribution in mouse models. This article reviews the strengths and limitations of in vivo antibody imaging methods with a focus on positron emission tomography and single-photon emission computed tomography and a brief discussion of the role of optical imaging in this application. A description of the basic principles behind the imaging techniques is provided along with a discussion of radiolabeling methods relevant to antibodies. Practical considerations of study design and execution are presented through a discussion of sensitivity and resolution tradeoffs for these techniques as defined by modality, signaling probe (isotope or fluorophore) selection, labeling method, and radiation dosimetry. Images and analysis results from a case study are presented with a discussion of output data content and relevant informatics gained with this approach to studying antibody pharmacokinetics.

High-resolution computed tomography of single breast cancer microcalcifications in vivo

Microcalcification is a hallmark of breast cancer and a key diagnostic feature for mammography. We recently described the first robust animal model of breast cancer microcalcification. In this study, we hypothesized that high-resolution computed tomography (CT) could potentially detect the genesis of a single microcalcification in vivo and quantify its growth over time. Using a commercial CT scanner, we systematically optimized acquisition and reconstruction parameters. Two ray-tracing image reconstruction algorithms were tested: a voxel-driven “fast” cone beam algorithm (FCBA) and a detector-driven “exact” cone beam algorithm (ECBA). By optimizing acquisition and reconstruction parameters, we were able to achieve a resolution of 104 μm full width at half-maximum (FWHM). At an optimal detector sampling frequency, the ECBA provided a 28 μm (21%) FWHM improvement in resolution over the FCBA. In vitro, we were able to image a single 300 μm X 100 μm hydroxyapatite crystal. In a syngeneic rat model of breast cancer, we were able to detect the genesis of a single microcalcification in vivo and follow its growth longitudinally over weeks. Taken together, this study provides an in vivo “gold standard” for the development of calcification-specific contrast agents and a model system for studying the mechanism of breast cancer microcalcification.

Implementation of a 3D topographic thinning model for assessing aerosol deposition of radioactive assays in small-animal CT/SPECT imaging

Nuclear imaging serves as an important tool for the visualization and analysis of nebulized radiolabeled particle deposition in the lung, enabling assessment of both nebulizer properties and lung function. To date, most research in this field has been focused on mathematical modeling from empirical data. This work examines the use of high-resolution 3D CT/SPECT imaging technology accompanied by automated lung segmentation to build a novel analysis model based on topographic thinning of the dual-modality tomograms.