QPS supports a wide range of studies for drug development, including quantitative whole-body autoradiography (QWBA) studies, which are conducted by our DMPK research team.
QWBA is a technique employed by researchers to determine the visual location and tissue distribution of radiolabeled compounds in various organs and tissues in the preclinical species. QWBA can be performed separately or combined with radiolabeled mass balance (MB) and plasma pharmacokinetic (PK) studies to provide high-resolution, quantitative data that can be used to characterize drug absorption, distribution, metabolism, and excretion (ADME) properties of drug candidates. QWBA is necessary to help scientists predict human exposure levels prior to a radiolabeled human AME study. This type of study is an integral component of the ADME package required for a New Drug Application (NDA) submission. Regulatory agencies require drug developers to characterize the ADME properties of prospective new drugs to ensure that patients are not exposed to dangerous levels of drugs or drug metabolites.
Performing a QWBA study can inform the following potential questions about the drug candidate of interest:
Before a QWBA study can begin, the researchers need the following information about the drug candidate:
To initiate a QWBA study, the researchers dose the radiolabeled compound to the animal of interest. At specified time-points post-dose (typically within 168 hours), the animal is humanely euthanized and the carcass is frozen. The carcass is then prepared in a solid block of embedding media. Next, a cryomicrotome is used to create thin sections of the whole animal carcass, and these sections are analyzed to determine where the compound is distributed in the body.
A single dose tissue distribution study yields valuable information that can be used to design toxicology and pharmacology experiments. In addition, the data produced by a single dose tissue distribution study is necessary to calculate the radioactive dose for a human AME study. For most compounds, a single dose tissue distribution study offers sufficient sensitivity and specificity regarding tissue distribution and the potential for accumulation.
Repeated dose tissue distribution studies can also be used, where necessary. Researchers determine the design and timing of repeated-dose tissue distribution studies on a case-by-case basis.
Alternative imaging strategies for QWBA imaging are currently being developed without radiolabels (i.e., MALDI-MSI); however, the most common QWBA imaging technique is phosphor imaging. The high-resolution images yielded through phosphor imaging can be enlarged to provide more depth and detail of the distribution in key tissues and organs. In addition to providing tissue concentrations for human dosimetry prediction, which is required for a human AME study, QWBA offers unique tools for investigating tissue pharmacokinetics, efficacy, toxicology, drug delivery, and disposition.
QPS has proven innovative study design and executional excellence for radiolabeled studies and there are several advantages of placing your study at QPS:
Completion of these preclinical DMPK studies, coupled with clinical PK and a radiolabel human mass balance and metabolite profiling study, will provide an ADME data package with exceptional scientific integrity and quality that will fully support a range of regulatory submissions.
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