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Quantitative Autoradiographic Method for Determination of Regional Rates of Cerebral Protein Synthesis In Vivo
Published on: June 28, 2019
Validation of procedures for quantitative whole-body autoradiography using digital imaging
P A Zane1, A J O'Buck, R E Walter
1Novartis Pharmaceuticals Corporation, Department of Drug Metabolism and Pharmacokinetics, Summit, NJ 07901, USA.
Digital analysis of autoradiograms accurately estimates tissue radioactivity concentrations, comparable to direct tissue sampling. This method offers a valuable alternative for radioactivity analysis in preclinical research.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Radiopharmaceutical Sciences
- Biomedical Imaging
Background:
- Quantitative whole-body autoradiography (QWBA) is crucial for assessing drug distribution.
- Direct tissue analysis is the gold standard but is labor-intensive.
- Digital analysis of autoradiograms offers a potentially more efficient method.
Purpose of the Study:
- To validate digital analysis of autoradiograms against direct tissue analysis for radioactivity quantification.
- To describe the preparation and calibration of standards for QWBA.
- To establish the reliability of digital imaging systems in radioactivity measurement.
Main Methods:
- Administered 14C radioactivity intravenously to male Long-Evans hooded rats.
- Performed whole-body autoradiography and collected blood and 16 tissue samples.
- Analyzed autoradiogram optical densities using a RAS3000 digital imaging system.
Main Results:
- Digital autoradiogram analysis showed high correlation (r=0.956) with direct tissue analysis.
- Linear regression revealed a near 1:1 correlation (slope=0.97, r2=0.913).
- Discrepancies in three tissues were attributed to cross-contamination during sample excision.
Conclusions:
- Digital analysis of autoradiograms provides comparable and reliable tissue radioactivity concentrations.
- This digital method serves as a valuable adjunct to conventional tissue analysis.
- The findings support the use of digital autoradiography for accurate pharmacokinetic studies.
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