[Histonet] RE: immunohistochemistry on drugs

From:"Steven Potts"

I’m also really curious if others have seen any protocols, using IHC for ADME type distribution tests.  This area has typically the domain of radiolabeling protocols, IHC would have some advantages if an assay could be developed.


What kind of drug (small molecule, biological, enzyme, antisense) would be the first question.  


I’ve found the following from a brief literature search:


If the drug happens to be an enzyme, it can of course be done:

For example, see Murray, GJ et al, Molecular Genetics and Metabolism  Volume 90, Issue 3, March 2007, Pages 307-312 “Cellular and tissue distribution of intravenously administered agalsidase alfa”.


If your drug is an antisense compound, this is done regularly:

For example, see Butler, M.  Neuroscience 131(3): 2005.  705-715.  Spinal distribution and metabolism of 2′-O-(2-methoxyethyl)-modified oligonucleotides after intrathecal administration in rats. 


Seems like you ought to be able to put a monoclonal antibody with DAB staining process specific for the drug, and see the distribution this way.  Anyone know of an example of a small molecule drug compound that someone did this with IHC?  Would it be as sensitive as direct radiolabelling?


I’d like to know the answer, because with whole slide scanning and computer measurements of IHC on a cell by cell basis, we could do very consistent quantitative of the drug expression level in tissue, provided there was a colorimetric approach to correlated with drug concentration in the tissue of interest.


Steve Potts, Ph.D.
Scientific Director, Biopharma 
Aperio Technologies
phone: (760)  539-1118
email: spotts@aperio.com
web: www.aperio.com  


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