Noninvasive In Vivo Optical Imaging Models for Safety and Toxicity Testing

Peterson, Jeffrey D.

doi:10.1016/b978-0-12-802147-7.00023-1

Cited by 5 publications

(9 citation statements)

References 93 publications

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“…Our previous studies with APAP established that even a single bolus drug dose induces obvious tissue histology changes (Peterson, 2016), and additional studies showed consistent detection of TAA- and CPZ-induced tissue damage with little or no obvious effects by RMP (data not shown). To understand the imaging results from RMP- and TAA-treated mice, in the context of overt tissue changes, we collected various tissues (liver, kidney, heart, spleen, stomach, and fat) from treated animals, and a trained pathologist assessed the hematoxylin and eosin–stained sections (Fig.…”

Section: Resultsmentioning

confidence: 63%

“…One of the most obvious biologic responses to explore as a readout was cell death, so we used an Annexin V–based NIR fluorescent imaging probe (AV-750) that has been used effectively in cancer treatment research (Zhao et al, 2015) and in preliminary liver injury studies (Peterson, 2016). Such a probe should be useful for assessing drugs known to induce hepatocellular liver toxicity that involves direct induction of cytotoxic liver apoptosis/necrosis.…”

Section: Resultsmentioning

confidence: 99%

“…Preliminary studies using AV-750 to assess different DILI-inducing chemical agents suggested that this probe is a sensitive detector of hepatocellular toxicity (Peterson, 2016) but may not be as effective in detecting other forms of liver injury such as cholestasis. In part, this may be due to our stringent requirement that our imaging system/probes detect liver changes after only a single compound administration, and this could be attributed, in part, to the additional mechanistic complexity in other forms of DILI in which additional time may be needed for inflammation or bile duct blockage events to occur.…”

Section: Resultsmentioning

confidence: 99%

“… a Probes that are commercially available with some validation data for use in preclinical drug-induced tissue injury applications (Peterson, 2016). …”

Section: Methodsmentioning

confidence: 99%

“…Although imaging of preclinical models of safety/toxicology has not been pursued extensively to date, the ability to use fluorescent imaging probes that detect and quantify a variety of biologic activities has considerable potential in this area as well (Amoozegar et al, 2012; Shuhendler et al, 2014; Peterson, 2016). In this study, three different types of NIR fluorescent probes—Annexin-Vivo 750 (AV-750), MMPSense 645 or 750 (MMP-645 or MMP-750), and Transferrin-Vivo 750 (TfV-750), specific for cell death, matrix metalloprotease (MMP) activity (inflammation), and transferrin receptor (metabolic activity) expression, respectively—were found to be excellent tools for detecting/characterizing drug-induced tissue injury in general and DILI in particular.…”

Section: Introductionmentioning

confidence: 99%

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Early Detection of Acute Drug-Induced Liver Injury in Mice by Noninvasive Near-Infrared Fluorescence Imaging

Vasquez

Peterson

2017

J Pharmacol Exp Ther

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Hepatocellular and cholestatic forms of drug-induced liver injury (DILI) are major reasons for late-stage termination of small-molecule drug discovery research projects. Biochemical serum markers are limited in their ability to sensitively and specifically detect both of these common DILI forms in preclinical models, and tissue-specific approaches to assessing this are labor intensive, requiring extensive animal dosing, tissue preparation, and pathology assessment. In vivo fluorescent imaging offers noninvasive detection of biologic changes detected directly in the livers of living animals. Three different near-infrared fluorescent imaging probes, specific for cell death (Annexin-Vivo 750), matrix metalloproteases (MMPSense 750 FAST), and transferrin receptor (Transferrin-Vivo 750) were used to measure the effects of single bolus intraperitoneal doses of four different chemical agents known to induce liver injury. Hepatocellular injury–inducing agents, thioacetamide and acetaminophen, showed optimal injury detection with probe injection at 18–24 hours, the liver cholestasis-inducing drug rifampicin required early probe injection (2 hours), and chlorpromazine, which induces mixed hepatocellular/cholestatic injury, showed injury with both early and late injection. Different patterns of liver responses were seen among these different imaging probes, and no one probe detected injury by all four compounds. By using a cocktail of these three near-infrared fluorescent imaging probes, all labeled with 750-nm fluorophores, each of the four different DILI agents induced comparable tissue injury within the liver region, as assessed by epifluorescence imaging. A strategy of probe cocktail injection in separate cohorts at 2 hours and at 20–24 hours allowed the effective detection of drugs with either early- or late-onset injury.

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Section: Resultsmentioning

confidence: 63%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“… a Probes that are commercially available with some validation data for use in preclinical drug-induced tissue injury applications (Peterson, 2016). …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Early Detection of Acute Drug-Induced Liver Injury in Mice by Noninvasive Near-Infrared Fluorescence Imaging

Vasquez

Peterson

2017

J Pharmacol Exp Ther

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Toxicity Potential of Nutraceuticals

Gupta

Srivastava²,

Lall³

2018

Methods in Molecular Biology

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By the turn of the twenty-first century, the use of nutraceuticals became increasingly popular in both humans and animals due to their easy access, cost-effectiveness, and tolerability with a wide margin of safety. While some nutraceuticals are safe, others have a toxic potential. For a large number of nutraceuticals, no toxicity/safety data are available due to a lack of pharmacological/toxicological studies. The safety of some nutraceuticals can be compromised via contamination with toxic plants, metals, mycotoxins, pesticides, fertilizers, drugs of abuse, etc. Knowledge of pharmacokinetic/toxicokinetic studies appears to play a pivotal role in safety and toxicity assessment of nutraceuticals. Interaction studies are essential to determine efficacy, safety, and toxicity when nutraceuticals and therapeutic drugs are used concomitantly. This chapter describes various aspects of nutraceuticals, particularly their toxic potential, and the factors influencing their safety.

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Paradigms in Fluorescence Molecular Imaging: Maximizing Measurement of Biological Changes in Disease, Therapeutic Efficacy, and Toxicology/Safety

Peterson

2018

Mol Imaging Biol

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Fluorescence molecular imaging (MI) is an important concept in preclinical research that focuses on the visualization of cellular and biological function in a non-invasive fashion to better understand in vivo disease processes and treatment effects. MI differs fundamentally from traditional preclinical imaging strategies in that it generally relies on reporter probes specific for particular targets or pathways that can be used to reveal biological changes in situ, at the site(s) of disease. In contrast, the more established imaging modalities, like magnetic resonance imaging, X-ray, micro X-ray computed tomography, and ultrasound, historically have relied primarily on late-stage anatomical or physiologic changes. The practical application of fluorescence MI, however, has drifted somewhat from the emphasis on quantifying biology, and based on the publication record, it now appears to include any imaging in which a probe or contrast agent is used to non-invasively acquire in vivo endpoint information. Unfortunately, the mere use of a defined biologically specific probe, in the absence of careful study design, does not guarantee that any useful biological information is actually gained, although often useful endpoint results still can be achieved. This review proposes to add subcategories of MI, termed MI biological assessment (or MIBA), that emphasize a focus on obtaining early and clear biological changes associated with disease development, therapeutic efficacy, and drug-induced tissue changes. Proper selection of probes and careful study design are critical for maximizing the non-invasive assessment of in vivo biological changes, and applications of these critical elements are described.

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Noninvasive In Vivo Optical Imaging Models for Safety and Toxicity Testing

Cited by 5 publications

References 93 publications

Early Detection of Acute Drug-Induced Liver Injury in Mice by Noninvasive Near-Infrared Fluorescence Imaging

Early Detection of Acute Drug-Induced Liver Injury in Mice by Noninvasive Near-Infrared Fluorescence Imaging

Toxicity Potential of Nutraceuticals

Paradigms in Fluorescence Molecular Imaging: Maximizing Measurement of Biological Changes in Disease, Therapeutic Efficacy, and Toxicology/Safety

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