Limits...
Development of a Novel Ligand, [C]TGN-020, for Aquaporin 4 Positron Emission Tomography Imaging.

Nakamura Y, Suzuki Y, Tsujita M, Huber VJ, Yamada K, Nakada T - ACS Chem Neurosci (2011)

Bottom Line: Considering its clinical relevance, it is highly desirable to develop a noninvasive method for the quantitative analysis of AQP distribution in humans under clinical settings.Currently, the method of choice for such diagnostic examinations continues to be positron emission tomography (PET).Utilizing [(11)C]-TGN-020, PET images were successfully generated in wild type and AQP4 mice, providing a basis for future evaluation regarding its suitability for clinical studies.

View Article: PubMed Central - PubMed

Affiliation: Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata , 1 Asahimachi, Niigata 951-8585, Japan.

ABSTRACT
Aquaporin 4 (AQP4), the most abundant isozyme of the water specific membrane transporter aquaporin family, has now been implicated to play a significant role in the pathogenesis of various disease processes of the nervous system from epilepsy to Alzheimer's disease. Considering its clinical relevance, it is highly desirable to develop a noninvasive method for the quantitative analysis of AQP distribution in humans under clinical settings. Currently, the method of choice for such diagnostic examinations continues to be positron emission tomography (PET). Here, we report the successful development of a PET ligand for AQP4 imaging based on TGN-020, a potent AQP4 inhibitor developed previously in our laboratory. Utilizing [(11)C]-TGN-020, PET images were successfully generated in wild type and AQP4 mice, providing a basis for future evaluation regarding its suitability for clinical studies.

No MeSH data available.


Related in: MedlinePlus

Time course analysis of SUV. Data from WT (n = 6, ○) and KO (n = 4, ◼) models are shown along with the standard error of means. (a) Brain, (b) skeletal muscle, and (c) heart.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3198134&req=5

fig3: Time course analysis of SUV. Data from WT (n = 6, ○) and KO (n = 4, ◼) models are shown along with the standard error of means. (a) Brain, (b) skeletal muscle, and (c) heart.

Mentions: Time course analyses are shown in Figure 3. Tissues having a significant distribution of AQP4, such as brain (Figure 3a) and skeletal muscle (Figure 3b) also showed a statistically significant higher [11C]TGN-020 uptake in the WT mice compared to those of the KO; P = 0.003 and 0.007, respectively. Conversely, tissues with no significant AQP4 distribution, such as heart (Figure 3c), appeared to have identical ligand uptake in the WT and KO animals (P = 0.2), confirming affinity of [11C]TGN-020 to AQP1. Time course analyses of other tissues are shown in the Supporting Information, along with a table of the corresponding standardized uptake value (SUV) data.


Development of a Novel Ligand, [C]TGN-020, for Aquaporin 4 Positron Emission Tomography Imaging.

Nakamura Y, Suzuki Y, Tsujita M, Huber VJ, Yamada K, Nakada T - ACS Chem Neurosci (2011)

Time course analysis of SUV. Data from WT (n = 6, ○) and KO (n = 4, ◼) models are shown along with the standard error of means. (a) Brain, (b) skeletal muscle, and (c) heart.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198134&req=5

fig3: Time course analysis of SUV. Data from WT (n = 6, ○) and KO (n = 4, ◼) models are shown along with the standard error of means. (a) Brain, (b) skeletal muscle, and (c) heart.
Mentions: Time course analyses are shown in Figure 3. Tissues having a significant distribution of AQP4, such as brain (Figure 3a) and skeletal muscle (Figure 3b) also showed a statistically significant higher [11C]TGN-020 uptake in the WT mice compared to those of the KO; P = 0.003 and 0.007, respectively. Conversely, tissues with no significant AQP4 distribution, such as heart (Figure 3c), appeared to have identical ligand uptake in the WT and KO animals (P = 0.2), confirming affinity of [11C]TGN-020 to AQP1. Time course analyses of other tissues are shown in the Supporting Information, along with a table of the corresponding standardized uptake value (SUV) data.

Bottom Line: Considering its clinical relevance, it is highly desirable to develop a noninvasive method for the quantitative analysis of AQP distribution in humans under clinical settings.Currently, the method of choice for such diagnostic examinations continues to be positron emission tomography (PET).Utilizing [(11)C]-TGN-020, PET images were successfully generated in wild type and AQP4 mice, providing a basis for future evaluation regarding its suitability for clinical studies.

View Article: PubMed Central - PubMed

Affiliation: Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata , 1 Asahimachi, Niigata 951-8585, Japan.

ABSTRACT
Aquaporin 4 (AQP4), the most abundant isozyme of the water specific membrane transporter aquaporin family, has now been implicated to play a significant role in the pathogenesis of various disease processes of the nervous system from epilepsy to Alzheimer's disease. Considering its clinical relevance, it is highly desirable to develop a noninvasive method for the quantitative analysis of AQP distribution in humans under clinical settings. Currently, the method of choice for such diagnostic examinations continues to be positron emission tomography (PET). Here, we report the successful development of a PET ligand for AQP4 imaging based on TGN-020, a potent AQP4 inhibitor developed previously in our laboratory. Utilizing [(11)C]-TGN-020, PET images were successfully generated in wild type and AQP4 mice, providing a basis for future evaluation regarding its suitability for clinical studies.

No MeSH data available.


Related in: MedlinePlus