The Probe for Renal Organic Cation Secretion (4-Dimethylaminostyryl)-N-Methylpyridinium (ASP+)) Shows Amplified Fluorescence by Binding to Albumin and Is Accumulated In Vivo
Accumulation of uremic toxins may lead to the life-threatening condition “uremic syndrome” in patients with advanced chronic kidney disease (CKD) requiring renal replacement therapy. Clinical evaluation of proximal tubular secretion of organic cations (OC), of which some are uremic toxins, is desire...
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SAGE Publishing
2022-01-01
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| Series: | Molecular Imaging |
| Online Access: | http://dx.doi.org/10.1155/2022/7908357 |
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| author | Jacob Schade Engbjerg Vincenzo Costanzo Donato Sardella Luca Bordoni Steen Jakobsen Luciano D'Apolito Jørgen Frøkiær Francesco Trepiccione Giovambattista Capasso Sebastian Frische |
| author_facet | Jacob Schade Engbjerg Vincenzo Costanzo Donato Sardella Luca Bordoni Steen Jakobsen Luciano D'Apolito Jørgen Frøkiær Francesco Trepiccione Giovambattista Capasso Sebastian Frische |
| author_sort | Jacob Schade Engbjerg |
| collection | DOAJ |
| description | Accumulation of uremic toxins may lead to the life-threatening condition “uremic syndrome” in patients with advanced chronic kidney disease (CKD) requiring renal replacement therapy. Clinical evaluation of proximal tubular secretion of organic cations (OC), of which some are uremic toxins, is desired, but difficult. The biomedical knowledge on OC secretion and cellular transport partly relies on studies using the fluorescent tracer 4-dimethylaminostyryl)-N-methylpyridinium (ASP+), which has been used in many studies of renal excretion mechanisms of organic ions and which could be a candidate as a PET tracer. This study is aimed at expanding the knowledge of the tracer characteristics of ASP+ by recording the distribution and intensity of ASP+ signals in vivo both by fluorescence and by positron emission tomography (PET) imaging and at investigating if the fluorescence signal of ASP+ is influenced by the presence of albumin. Two-photon in vivo microscopy of male Münich Wistar Frömter rats showed that a bolus injection of ASP+ conferred a fluorescence signal to the blood plasma lasting for about 30 minutes. In the renal proximal tubule, the bolus resulted in a complex pattern of fluorescence including a rapid and strong transient signal at the brush border, a very low signal in the luminal fluid, and a slow transient intracellular signal. PET imaging using 11C-labelled ASP+ showed accumulation in the liver, heart, and kidney. Fluorescence emission spectra recorded in vitro of ASP+ alone and in the presence of albumin using both 1-photon excitation and two-photon excitation showed that albumin strongly enhance the emission from ASP+ and induce a shift of the emission maximum from 600 to 570 nm. Conclusion. The renal pattern of fluorescence observed from ASP+ in vivo is likely affected by the local concentration of albumin, and quantification of ASP+ fluorescent signals in vivo cannot be directly translated to ASP+ concentrations. |
| format | Article |
| id | doaj-art-d9a2d3e7a18f40ff8556f3840fd65c16 |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-d9a2d3e7a18f40ff8556f3840fd65c162025-01-03T00:11:57ZengSAGE PublishingMolecular Imaging1536-01212022-01-01202210.1155/2022/7908357The Probe for Renal Organic Cation Secretion (4-Dimethylaminostyryl)-N-Methylpyridinium (ASP+)) Shows Amplified Fluorescence by Binding to Albumin and Is Accumulated In VivoJacob Schade Engbjerg0Vincenzo Costanzo1Donato Sardella2Luca Bordoni3Steen Jakobsen4Luciano D'Apolito5Jørgen Frøkiær6Francesco Trepiccione7Giovambattista Capasso8Sebastian Frische9Department of BiomedicineDepartment of ExperimentalDepartment of BiomedicineDepartment of BiomedicineDepartment of Nuclear Medicine and PET CenterBiogem Institute of Molecular Biology and GeneticsDepartment of Nuclear Medicine and PET CenterBiogem Institute of Molecular Biology and GeneticsBiogem Institute of Molecular Biology and GeneticsDepartment of BiomedicineAccumulation of uremic toxins may lead to the life-threatening condition “uremic syndrome” in patients with advanced chronic kidney disease (CKD) requiring renal replacement therapy. Clinical evaluation of proximal tubular secretion of organic cations (OC), of which some are uremic toxins, is desired, but difficult. The biomedical knowledge on OC secretion and cellular transport partly relies on studies using the fluorescent tracer 4-dimethylaminostyryl)-N-methylpyridinium (ASP+), which has been used in many studies of renal excretion mechanisms of organic ions and which could be a candidate as a PET tracer. This study is aimed at expanding the knowledge of the tracer characteristics of ASP+ by recording the distribution and intensity of ASP+ signals in vivo both by fluorescence and by positron emission tomography (PET) imaging and at investigating if the fluorescence signal of ASP+ is influenced by the presence of albumin. Two-photon in vivo microscopy of male Münich Wistar Frömter rats showed that a bolus injection of ASP+ conferred a fluorescence signal to the blood plasma lasting for about 30 minutes. In the renal proximal tubule, the bolus resulted in a complex pattern of fluorescence including a rapid and strong transient signal at the brush border, a very low signal in the luminal fluid, and a slow transient intracellular signal. PET imaging using 11C-labelled ASP+ showed accumulation in the liver, heart, and kidney. Fluorescence emission spectra recorded in vitro of ASP+ alone and in the presence of albumin using both 1-photon excitation and two-photon excitation showed that albumin strongly enhance the emission from ASP+ and induce a shift of the emission maximum from 600 to 570 nm. Conclusion. The renal pattern of fluorescence observed from ASP+ in vivo is likely affected by the local concentration of albumin, and quantification of ASP+ fluorescent signals in vivo cannot be directly translated to ASP+ concentrations.http://dx.doi.org/10.1155/2022/7908357 |
| spellingShingle | Jacob Schade Engbjerg Vincenzo Costanzo Donato Sardella Luca Bordoni Steen Jakobsen Luciano D'Apolito Jørgen Frøkiær Francesco Trepiccione Giovambattista Capasso Sebastian Frische The Probe for Renal Organic Cation Secretion (4-Dimethylaminostyryl)-N-Methylpyridinium (ASP+)) Shows Amplified Fluorescence by Binding to Albumin and Is Accumulated In Vivo Molecular Imaging |
| title | The Probe for Renal Organic Cation Secretion (4-Dimethylaminostyryl)-N-Methylpyridinium (ASP+)) Shows Amplified Fluorescence by Binding to Albumin and Is Accumulated In Vivo |
| title_full | The Probe for Renal Organic Cation Secretion (4-Dimethylaminostyryl)-N-Methylpyridinium (ASP+)) Shows Amplified Fluorescence by Binding to Albumin and Is Accumulated In Vivo |
| title_fullStr | The Probe for Renal Organic Cation Secretion (4-Dimethylaminostyryl)-N-Methylpyridinium (ASP+)) Shows Amplified Fluorescence by Binding to Albumin and Is Accumulated In Vivo |
| title_full_unstemmed | The Probe for Renal Organic Cation Secretion (4-Dimethylaminostyryl)-N-Methylpyridinium (ASP+)) Shows Amplified Fluorescence by Binding to Albumin and Is Accumulated In Vivo |
| title_short | The Probe for Renal Organic Cation Secretion (4-Dimethylaminostyryl)-N-Methylpyridinium (ASP+)) Shows Amplified Fluorescence by Binding to Albumin and Is Accumulated In Vivo |
| title_sort | probe for renal organic cation secretion 4 dimethylaminostyryl n methylpyridinium asp shows amplified fluorescence by binding to albumin and is accumulated in vivo |
| url | http://dx.doi.org/10.1155/2022/7908357 |
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