Skip to content
Molecules
SEKISUI XenoTech DD Blog Logo

What You Need to Know About Micro-Autoradiography (mARG) Distribution Studies

In vivo determination of drug localization in tissue can be uniquely informative to drug developers investigating distribution within the context of the ADME/pharmacokinetic profile of their drug compounds. Micro-autoradiography can demonstrate sites of accumulation of a drug and drug-related material, which can be used as supplemental data for evaluation of parameters such as toxicity, efficacy, drug penetration, or differential metabolite distribution.
 
Micro-autoradiography histology techniques utilize photographic detection media (Nuclear Emulsion) to spatially locate drug-derived radioactivity at the cellular level in organ and tissue samples. Therefore, it provides opportunity for a more detailed examination than QWBA because microscopic radioactivity distribution can be analyzed in target tissues.

Our approach to radiolabeled ADME in drug discovery and development

Our Drug Development Solutions Center in Tokai, Japan, has been offering micro-autoradiography (mARG) as a tissue distribution analytical method for more than 30 years, accumulating a wealth of experience in histology, drug deposition, and radioactivity. Like other radiolabeled ADME services, mARG requires a high degree of technical skill and our team at DDSC has extensive experience and training to provide you consistent sections, precise qualitative analysis, and educated interpretation of results.

mARG
Rat Thyroid gland Dyeing: HE
mARG Rat
: Radioactivity (silver grains)

Microautoradiography showing accumulation in the follicles of rat thyroid gland after repeated administration

Used as supplemental data for evaluation of toxicity

F:Follicles
CT:Connective tissue
FC:Follicular cells
PC:Parafollicular cells

mARG study highlights

  • Specialized thaw mount method
  • AAALAC-accredited facility; 150,000 ft campus featuring animal care units
  • Consistent 5 μm slices exposed to nuclear emulsion for radioactive compound visualization
  • HE stained slides for reference
  • 4-week turnaround time for data/report

Method

Fresh tissue or organ samples are snap-frozen, cryosectioned at 5 μm thickness, and exposed to nuclear emulsion that has been put on glass microscope slide for 1 – 4 weeks. After the exposure, the slides are developed, stained, and analyzed using a Leica LEITZ LMR light microscope to visually distinguish the localization of the radioactive drug derivative in individual cells.

Additional quantitative comparison

Consecutive 5 μm mARG horizontal skin slices may be considered together to better understand drug penetration in terms of depth. The figure below shows our capabilities to create a histogram from data from multiple skin slices, at 20 um intervals, to quantify radioactivity at sequential depths.

Drug penetration in skin sections with histogram to inform quantitative distribution data

sg:Sebaceous glands
de:Dermis
ep:Epidermis
sc:Stratum corneum
hf:Hair follicle

SEKISUI XenoTech offers the following options:

Tissue capabilities

  • Adrenal Gland
  • Brain
  • Lung
  • Liver
  • Intestine
  • Kidney
  • Muscle
  • Pancreas
  • Retina
  • Skin
  • Spleen
  • Thyroid Gland
  • Tumor
  • Other tissue types maybe possible upon request

Radionuclides

  • 14C
  • 3H
  • 125I
  • 33P
  • 35S
  • 51Cr
  • 111In
  • 55Fe
  • 59Fe
  • 65Zn
  • 75Se
  • 90Y
  • 153Gd

Animal species

  • Rat
  • Mouse
  • Rabbit
  • Dog
  • Monkey
  • Miniature Pig
  • Animal models of human disease
  • Knock Out animals
  • Chimeric Mice with highly humanized liver
  • Others may be available upon request

Contact Us with Questions, Feedback or Requests

Learn more about:

[1] M3 (R2) https://www.fda.gov/media/71542/download
[2] 21CFR312.23 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?FR=361.1
[3] https://www.bioanalysis-zone.com/2018/03/09/quantitative-whole-body-autoradiography-qwba-imaging-mass-spectrometry-ims-can-ims-replace-qwba-support-regulated-drug-discovery-development/

About the Authors

Jolanta Golec has been with the SEKISUI Drug Development Solutions Center, our sister lab in Tokai, Japan, since 2013. She has experience serving in both scientific research and sales promotional capacities. Jolanta holds a M.Eng. in Agriculture from the University of Agriculture in Krakow (Poland), M.Sc. in Pharmaceutical Biotechnology from the University College Cork (Ireland) and is working on her MBA from the University of Manchester (UK).
Madison (Knapp) Esely-Kohlman received her BS from the University of Missouri – Columbia and is currently SEKISUI XenoTech’s Marketing Communication Specialist, developing scientific content that communicates the value and expertise of internal contract service and test system production teams. Madison joined SEKISUI XenoTech as the Scientific Communications Coordinator in 2019 after serving in similar positions at CropLife America, Bond Life Sciences Center and the University of Missouri CAFNR Office of Communications.

Subscribe to our Newsletter

Stay up to date with our news, events and research

In vitro pipette test article treatment
005 International Messaging Created with Sketch.

Do you have a question or a request for upcoming blog content?

We love to get your feedback

A scientist utlilizing a microplate