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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JPIAMR Diagnostics Call / James Bond’s occupational exposures

Dear All, A short one today! Please peruse both the funding opportunities and upcoming meetings just below my signature. Of special note: Building on the call in the recent biodefense-focused BAA from NIAID for diagnostic applications, JPIAMR is also looking for diagnostic applications (7 Mar deadline). Very interesting 2 Mar 2023 Duke-Margolis webinar entitled “Data Capture

NIAID BAA – Biodefense focus / Fireside Chat on diagnostics and more

Dear All, We are swimming in Broad Agency Announcements aka BAAs! As a refresher, I recently shared a BAA from the CDC and one from BARDA — now we have another one from NIAID! There’s a strong biodefense angle here with lots of scope. Key details of each opportunity are as follows and I highly recommend you check

LPAD/Limited Use insights; NI margins for TB and candidiasis

Dear All,  I want to call your attention to next week’s AMDAC (Antimicrobial Drugs Advisory Committee) for rezafungin. This meeting is Tue 24 Jan 2023, 9a-4.30p ET and the meeting materials are provided here.  Rezafungin is an antifungal but please don’t let that dissuade you from attending: this AMDAC promises to be an important discussion

Notable webinars: Pediatric drug development; Drug delivery systems

Dear All, The high-value webinars below have just crossed my radar.  First up, we have a very important 2-part webinar on pediatric antibacterial drug development entitled “Improving the Investigation of New Antibacterial Agents for Use in Children: Ensuring That Our Youngest Patients Also Benefit from Innovative Treatments of Infections Caused by Multi-Drug Resistant Bacteria.” Here are the

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