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Abstract #4409

Measurements of Kinetic Stability, Blood-Brain Barrier Permeability and Cytotoxicity for Two Thulium Based Contrast Agents

Daniel Coman1,2, Margarita Gattas-Sethi1, Hubert K.F. Trubel3,4, Peter Herman1,5, Fahmeed Hyder2,6, Garry Kiefer7, Francesco dErrico6

1Department of Diagnostic Radiology, Yale University, New Haven, CT, USA; 2Quantitative Neuroscience with Magnetic Resonance (QNMR), Yale University, New Haven, CT, USA; 3Bayer HealthCare Research Center, Wuppertal, Germany; 4Department of Pediatrics, HELIOS-Klinikum Wuppertal, University Witten/Herdecke, Wuppertal, Germany; 5Semmelweis University, POB 448, H-1446, Budapest, Hungary; 6Departments of Diagnostic Radiology and Biomedical Engineering, Yale University, New Haven, CT, USA; 7Macrocyclics, Dallas, TX 75235, USA

In the last decade, a new non-invasive method for temperature and pH determination was developed based on temperature and pH dependencies of the 1H chemical shifts emanating from TmDOTP5-. More recently a similar temperature-sensitive probe was introduced, based on temperature dependence of the methyl 1H chemical shift of TmDOTMA-, which is pH independent. Our results show that these two agents are kinetically stable, they cross the blood-brain barrier, they clearly show the lack of any acute toxicity effects on Chinese hamster lung cells and they demonstrate that the brains activity is unaffected by their presence in the extracellular space.