The continuing education course "Non-Invasive Imaging as a Problem-Solving Tool and Translational Biomarker Strategy in Toxicologic Pathology" provided a thorough overview of commonly used imaging modalities and the logistics required for integration of small animal imaging into toxicologic pathology. Non-invasive imaging (NIN) is gaining acceptance as an important modality in toxicologic pathology. This technology allows nonterminal, time-course evaluation of functional and morphologic endpoints and can be used to translate biomarkers between preclinical animal models and human patients. NIN can support drug development as well as basic research in academic or industrial environments. An initial overview of theoretical principles was followed by focused presentations on magnetic resonance imaging (MRI)/magnetic resonance microscopy (MRM), positron emission tomography (PET)/single proton emission computed tomography (SPECT), ultrasonography (US, primarily focused on echocardiography), optical (bioluminescent) imaging, and computed tomography (CT). The choice of imaging modality will depend on the research question and the needed resolution.
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http://dx.doi.org/10.1177/0192623310390392 | DOI Listing |
Hum Exp Toxicol
January 2025
AnaPath Services GmbH/K. Weber Consulting GmbH, Oberbuchsiten, Switzerland.
Managing conflicts of interest (COIs) in scientific decision-making is important for minimizing bias and fostering public trust in science. Proper management of COIs has added significance when scientists are making decisions that impact public policy, such as assessing substances for carcinogenicity. The International Agency for Research on Cancer (IARC) organizes expert working groups to identify putative carcinogens and determine whether or not the hazard is likely to present significant potential harm to humans.
View Article and Find Full Text PDFToxicol Pathol
January 2025
Novartis Institute for Biomedical Research, Cambridge, Massachusetts, USA.
The safety of a 2'--methoxyethyl antisense oligonucleotide (ASO) was investigated in Mauritius cynomolgus monkeys in a 41-week Good Laboratory Practice (GLP) toxicity study after multiple intrathecal (IT) administrations. Histopathological examination revealed ectopic formation of lymphoid follicles in the spinal cord (SC) at the injection site at all doses and the presence of granular material in neurons of the SC in high-dose animals. The granular material was seen in all the segments of the SC, but mainly in the lumbar segment and persisted at the end of the 26-week recovery period, while the lymphoid follicles showed a reversibility trend.
View Article and Find Full Text PDFToxicol Pathol
January 2025
Eli Lilly and Company, Indianapolis, Indiana, USA.
Nonhuman primates (NHPs) have been and remain a highly valuable animal model with an essential role in translational research and pharmaceutical drug development. Based on current regulatory guidelines, the nonclinical safety of novel therapeutics should be evaluated in relevant nonclinical species, which commonly includes NHPs for biotherapeutics. Given the practical and ethical limitations on availability and/or use of NHPs and in line with the widely accepted guiding "3Rs" (replace, reduce, and refine) principles, many approaches have been considered to optimize toxicity study designs to meaningfully reduce the number of NHPs used.
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