Quantitative Tissue Distribution and QWBA

When you work with BOC Sciences, you can leverage our state-of-the-art facilities and experience and expertise in tissue distribution studies and quantitative whole-body autoradiography (QWBA) to evaluate your drug candidates to understand the relationship between the distribution and accumulation of your compounds and/or their metabolites, to reveal tissue-specific activity, and to identify potential toxicity. Which method is right for you?

Introduction to Quantitative Tissue Distribution Studies

Drug tissue distribution is a complex process that relies on a long list of parameters that affect the delivery, retention, and removal of drugs into and out of biological tissue.

Single-dose tissue distribution studies provide information for designing toxicology and pharmacology experiments and for interpreting the results of these studies.

Repeat dose tissue distribution studies are designed for compounds with longer half-lives in tissue compared to plasma, drugs for site-specific targeted delivery systems, incomplete elimination or unanticipated organ toxicity.

Tissue distribution studies play a vital role in drug development programs:

• The concentration of the drug in the tissue is directly related to the pharmacological effect
• The concentration of the drug in the blood is directly related to the pharmacological effect (Plasma drug concentrations reflect the condition of the drug in the body (target organ))
• In general, it is easier to detect the concentration of a drug in blood than in tissue, so blood concentrations are generally used instead of tissue concentrations
• When the distribution of the drug in the tissue is extremely heterogeneous, it is more reasonable and scientific to detect the concentration of drugs in tissues
• Tissue distribution studies can improve drug efficacy, reduce toxicity, and guide formulation design

Traditionally, investigations have been carried out by conventional methods, such as tissue dissection, total radioactivity determination, and LC-MS-MS/QPCR. However, the advent of quantitative whole-body autoradiography (QWBA) has revolutionized drug distribution studies by utilizing fluorescence imaging techniques and providing high resolution images.

Introduction to QWBA

QWBA is a powerful tool for studying the systemic distribution of subjects and the elimination patterns of radiolabelled drugs in various tissues. Its advantages include:

• High resolution
• Wide range of substances
• Full range of organization
• Full-time span
• Quantifiable

QWBA can be performed alone or in combination with radiolabeled mass balance (MB) and plasma pharmacokinetic (PK) studies to provide high-resolution quantitative data candidates that can be used to characterize drug absorption, distribution, metabolism and excretion (ADME) properties.

Fig. 1 Autoradiograms of selected sections of mice at 48 h after dosing with [³H]BMS-753493 (Shen H, 2016)

Our Quantitative Tissue Distribution and QWBA Services

To initiate a QWBA study, our researchers administered radiolabeled compounds to animals of interest. At a specific time point after administration (usually within 168 hours), the animals are humanely euthanized and the carcasses are frozen. The carcass is then prepared in a solid block embedded in a medium. Next, thin sections of the entire animal carcass are created using a cryostat and these sections are analyzed to determine where the compound is distributed in the body.

Tissue Distribution/QWBA Studies Applications

• Tissue distribution
• Target organ/tissue validation
• Correlation with histopathology
• Tumor penetration
• Support microkernel test
• Skin/nail penetration
• Human dosimetry calculations
• Placental metastasis
• Penetration of blood-brain barrier

Our Advantages

• Evaluate specific information through objective-driven research design
• Study design consultation
• Pharmacokinetic (PK) analysis
• Dosimetric calculations
• State-of-the-art laboratory capabilities
• Rapid turnaround of imaging studies to support drug discovery

Quotation and Ordering

As with all of our live services, we make sure to keep in touch during the study. If you have any special needs or questions about our services, please feel free to contact us to support our experienced experts. We look forward to working with you in the future.