A revolutionary imaging method pinpoints the exact places in the tissues where drugs bind: it will help better prevent adverse effects.
What path do the drugs we take take once they enter our body? Do they go straight to their target or do they also interact with other tissues? Which cells do they bind to? Until now, these questions could only be answered in a rather vague way. Now, however, a new imaging technique developed by a group of American chemists has made it possible to trace, with “surgical” precision, the exact destination of the drugs administered to some mice, illuminating the individual cells to which they were bound.
The procedure, described in the magazine Cellwill allow us to see in advance, still in the research phase, whether a medicine ends up on unwanted targets, and to take action by minimizing side effects. Not only that: being able to follow the journey of drugs with this degree of precision will help to understand whether a certain molecule is going exactly where it is needed, or to better understand the mechanism of effectiveness of widely used medicines.
An upgrade of a known technique
In 2022, a group of scientists from Scripps Research and the Howard Hughes Medical Institute (United States) led by Li Ye, Professor of Chemistry and Chemical Biology in Neuroscience, had developed a method to highlight the cells to which drugs bind on the surface of organs. The technique, called CATCH, consists of inserting chemical labels into covalent drugs, that is, those that bind to their targets permanently, through stable chemical bonds.
Once the drugs have been delivered, the tissues to be examined are taken and treated with fluorescent substances together with a copper molecule which, with a highly precise and selective reaction (a Nobel technique called “click chemistry”), binds these “highlighters” to the initial chemical label. This reveals where each drug molecule ended up.
The CATCH technique works, however, only on the surface of the organs and not in depth, because the proteins in the tissues absorb the copper necessary for the chemical reaction described, preventing it from penetrating into the lower layers. The evolution of the method, called vCATCH, solved this obstacle and made it possible to follow the path of the drugs throughout the entire organism of mice.
Help from AI
Tissues to be analyzed were pretreated with excess copper to block drug-binding sites with cells, and then subjected to eight repeated baths in both copper and fluorescent labels. Since the chemical reactions to be visualized are highly selective, this overabundance of substances created no background noise.
The use of artificial intelligence made it possible to automatically identify drug-related cell images within several terabytes of image data generated for each mouse.
Anti-cancer and adverse effects
Scientists tested the vCATCH technique to map the link between two anticancer drugs and mouse cells. So they realized that one of the two drugs, used to treat blood cancers, bound – unexpectedly – not only to its targets in the blood, but also to immune cells in the liver, heart tissue and blood vessels. This previously unknown activity explains some known side effects of the drug, which can cause irregular heartbeat and bleeding problems.
In the future, the technique will allow us to understand in advance, before clinical trials, whether a medicine binds to off-target tissues and whether this could generate potential side effects; but also to see if a cancer drug acts only on diseased cells, sparing healthy ones, or on which brain cells an antidepressant has an effect.
