Andre F. Martins
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martinslab.bsky.social
Andre F. Martins
@martinslab.bsky.social
Dad, researcher, husband, like water sports, music and science. Professor at the Werner Siemens Imaging Center, Tübingen. #Humboldtian #Sofja_Kovalevskaja
Thank you! ☺️
February 18, 2025 at 11:59 AM
Metabolic PCTA-Based Shift Reagents for the Detection of Extracellular Lactate Using CEST MRI
Lactate is a key metabolic driver in oncology and immunology. Even in the presence of physiological oxygen levels, most cancer cells upregulate anaerobic glycolysis, resulting in abnormal lactate production and accumulation in the tumor microenvironment. The development of more effective, sensitive, and safe probes for detecting extracellular lactate holds the potential to significantly impact cancer metabolic profiling and staging significantly. Macrocyclic-based PARACEST agents have been reported to act as shift reagents (SRs) and detect extracellular lactate via chemical exchange saturation transfer (CEST) MRI. Here, we introduce a new family of SRs based on the PCTA ligand, an inherently stable and kinetically inert group of molecules with the potential for (pre)clinical translation. We observed that Yb-PCTA and Eu-PCTA can significantly shift lactate –OH signals in the CEST spectra. In vitro, CEST MRI experiments proved that imaging extracellular lactate specifically with these complexes is feasible even in the presence of competing small metabolites in blood and in the tumor microenvironment. In vivo preclinical imaging showed that Yb-PCTA can be safely administered intravenously in mice to detect extracellular lactate noninvasively. This work contributes to the field of precision imaging in medicine and provides evidence that the PCTA-ligand is a valuable scaffold for developing molecular and metabolic imaging sensors.
pubs.acs.org
February 11, 2025 at 3:31 PM
And more is yet to come! Stay tuned to the next developments from the team on compartmentalized metabolism. 🙂
February 11, 2025 at 3:24 PM
Check out our latest publication on this discovery and its potential impact: pubs.acs.org/doi/10.1021/ja… @pubs.acs.org @acs.or#Metabolisms#MRIR#CESTS#Cancerer
https://pubs.acs.org/doi/10.1021/ja…
February 11, 2025 at 3:24 PM
That unexpected result sparked years of work @unituebingen.bsky.social @wsic.bsky.social developed better, safer agents and now have a clear way to detect extracellular lactate in tissues—including tumors. A small experiment led to something really cool!
February 11, 2025 at 3:24 PM
I asked the student to mix metabolites with an inglorious contrast agent and check CEST signals at wider NMR regions. Expecting maybe one bound water signal, we never imagined seeing the OH from lactate shift so clearly away from water—with a beautifully defined CEST!
February 11, 2025 at 3:24 PM
Me also!
November 23, 2024 at 8:38 PM