High-resolution (effectively 3-D) drug concentration measurements in tissues

Dear All: 

I’m really not trying to flood your inbox with email, but when ideas surface I do like to pass them on.

As an instructive follow-on to the email earlier this week about continuous in vivo measurements of drug concentrations, David Perlin made me aware of a use of MALDI that I’d not previously considered. Called MALDI-MSI (matrix-assisted laser desorption/ionization mass spectrometric imaging), the idea is that the MALDI technology is used to scan across a tissue slice. Data collected at each x-y location are assembled to produce a heatmap for ionization signals that have been shown to correspond to the desired analyte.

As an example of this, David’s group just published a paper in AAC (Zhao et al., doi:10.1128/AAC.01009-17) in which they used this technique to look at the distribution of echinocandins in experimental candidiasis. Here’s a pair of images from the paper: At top you have the heatmap for the candin (red = more) and at bottom a view of a corresponding H&E stain. Clever!​

This technique has been used in cancer and TB (see additional citations just below my signature). There’s even a society dedicated to this technology. I look forward to seeing additional uses of technique … we’ve long wanted to have a better understanding of PK-PD at tissue sites and this tool certainly creates new possibilities.

All best wishes, –jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Chief Strategy Officer, CARB-X | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: http://amr.solutions/blog.html

Some additional papers using this idea
Spatial distribution of veliparib measured by matrix-assisted laser desorption ionization mass spectrometry in triple-negative breast cancertumors.
Prideaux B, Hann B, Krings G, Coppe JP, Brown Swigart L, Lee EP, Esserman L, Yee D, Wolf D, Savic RM. J Clin Oncol. 2014 Sep 10;32(26_suppl):161.

The association between sterilizing activity and drug distribution into tuberculosis lesions.
Prideaux B, Via LE, Zimmerman MD, Eum S, Sarathy J, O’Brien P, Chen C, Kaya F, Weiner DM, Chen PY, Song T, Lee M, Shim TS, Cho JS, Kim W, Cho SN, Olivier KN, Barry CE 3rd, Dartois V. Nat Med. 2015 Oct;21(10):1223-7.

Upcoming meetings of interest to the AMR community:


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Dear All, I was fascinated by this recent paper in AAC: Neha K. Prasad, Ian B. Seiple, Ryan T. Cirz, and Oren S. Rosenberg. Leaks in the Pipeline: a Failure Analysis of Gram-Negative Antibiotic Development from 2010 to 2020. Antimicrob Agents Chemother. 2022 May 17;66(5):e0005422. doi:10.1128/aac.00054-22. (Addendum: This newsletter has a follow-up newsletter.) In brief,

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