Contributions
Abstract: P1259
Type: Poster Sessions
Abstract Category: Therapy - Tools for detecting therapeutic response
Background: A high variability in in vivo drug action makes the treatment of Multiple Sclerosis (MS) challenging, further limiting the prediction of therapeutic outcome. Due to its three fluorine (19F) atoms, the anti-inflammatory drug teriflunomide (TF) could be detected non-invasively by 19F magnetic resonance (MR) and tracked in vivo during disease. The ultimate goal is to support therapeutic adjustments by determining drug concentrations in vivo using 19F MR imaging (MRI) and spectroscopy (MRS).
Methods: MR experiments were performed on a Bruker Biospec 9.4T MR Scanner using dual-tunable 19F/1H coils for parallel 1H MRI (anatomy) and 19F MRI (drug) as well as cryogenically cooled coils (CRP) for in vivo 19F MRS. T1-mapping was performed using a RARE sequence with variable repetition times. T2-mapping was performed using a multi-slice multi-echo technique with different echo times. Different sequences were used to image phantoms and animals in vivo and ex vivo. TF was administered to healthy Dark Agouti (DA) rats and experimental autoimmune encephalomyelitis (EAE) mice (SJL and C57BL/6) prior to MRI measurements. 1H MRI was performed with contrast agent to determine blood brain barrier leakage. 19F MRS was used to detect the 19F signal of TF. Animals were killed and organs fixed for ex vivo studies.
Results: In phantom studies, the 19F NMR properties of TF were determined. The relaxation times were measured (T1=947ms, T2=461ms) and a temperature influence on T1 and T2 was found. The contrast agent gadolinium had a T1 shortening effect, a linear correlation of pH and signal intensity was found and limits of detection were determined. The drug could be detected and followed in vivo in the stomach of healthy DA rats. Ex vivo, TF was detected in the liver, kidney, stomach and feces, but not in the brain. In EAE mice, TF could be detected in the head and abdominal region, using a 19F CRP.
Discussion: Here we determined the 19F NMR properties of TF, and showed that these are dependent on temperature, pH and presence of contrast agent. We also showed the first in vivo and ex vivo detection of TF using 19F MR. These results will be used to optimize the MR scan parameters for future in vivo experiments using TF therapy. Tracking 19F compounds non-invasively could provide invaluable insights into drug distribution especially during pathology. The future goal is to transfer this to the clinic, to provide individualized therapy monitoring tailored to patient's needs.
Disclosure: CP: has received presentation fees from Sanofi.
JMM: has received presentation fees from Novartis.
AP: nothing to disclose.
TN: is founder and CEO of MRI.TOOLS GmbH, chair of the Highfield and Applications study group of the International Society of Magnetic Resonance in Medicine, and has received travel funds from Siemens Healthcare.
SW: reports research grants from Novartis and Genzyme and presentation fees from Novartis.
Abstract: P1259
Type: Poster Sessions
Abstract Category: Therapy - Tools for detecting therapeutic response
Background: A high variability in in vivo drug action makes the treatment of Multiple Sclerosis (MS) challenging, further limiting the prediction of therapeutic outcome. Due to its three fluorine (19F) atoms, the anti-inflammatory drug teriflunomide (TF) could be detected non-invasively by 19F magnetic resonance (MR) and tracked in vivo during disease. The ultimate goal is to support therapeutic adjustments by determining drug concentrations in vivo using 19F MR imaging (MRI) and spectroscopy (MRS).
Methods: MR experiments were performed on a Bruker Biospec 9.4T MR Scanner using dual-tunable 19F/1H coils for parallel 1H MRI (anatomy) and 19F MRI (drug) as well as cryogenically cooled coils (CRP) for in vivo 19F MRS. T1-mapping was performed using a RARE sequence with variable repetition times. T2-mapping was performed using a multi-slice multi-echo technique with different echo times. Different sequences were used to image phantoms and animals in vivo and ex vivo. TF was administered to healthy Dark Agouti (DA) rats and experimental autoimmune encephalomyelitis (EAE) mice (SJL and C57BL/6) prior to MRI measurements. 1H MRI was performed with contrast agent to determine blood brain barrier leakage. 19F MRS was used to detect the 19F signal of TF. Animals were killed and organs fixed for ex vivo studies.
Results: In phantom studies, the 19F NMR properties of TF were determined. The relaxation times were measured (T1=947ms, T2=461ms) and a temperature influence on T1 and T2 was found. The contrast agent gadolinium had a T1 shortening effect, a linear correlation of pH and signal intensity was found and limits of detection were determined. The drug could be detected and followed in vivo in the stomach of healthy DA rats. Ex vivo, TF was detected in the liver, kidney, stomach and feces, but not in the brain. In EAE mice, TF could be detected in the head and abdominal region, using a 19F CRP.
Discussion: Here we determined the 19F NMR properties of TF, and showed that these are dependent on temperature, pH and presence of contrast agent. We also showed the first in vivo and ex vivo detection of TF using 19F MR. These results will be used to optimize the MR scan parameters for future in vivo experiments using TF therapy. Tracking 19F compounds non-invasively could provide invaluable insights into drug distribution especially during pathology. The future goal is to transfer this to the clinic, to provide individualized therapy monitoring tailored to patient's needs.
Disclosure: CP: has received presentation fees from Sanofi.
JMM: has received presentation fees from Novartis.
AP: nothing to disclose.
TN: is founder and CEO of MRI.TOOLS GmbH, chair of the Highfield and Applications study group of the International Society of Magnetic Resonance in Medicine, and has received travel funds from Siemens Healthcare.
SW: reports research grants from Novartis and Genzyme and presentation fees from Novartis.