Synthesis of a high specific activity 125I-labeled analog of PK 11195, potential agent for SPECT imaging of the peripheral benzodiazepine binding site
| Autor: | David L. Gildersleeve, James M. Olson, Anne B. Young, Brian J. Ciliax, Tay Yean Lin, Donald M. Wieland |
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| Rok vydání: | 1989 |
| Předmět: |
Male
PK-11195 Stereochemistry In Vitro Techniques High-performance liquid chromatography Iodine Radioisotopes chemistry.chemical_compound In vivo Glioma Spect imaging medicine Radioligand Animals Humans Chromatography High Pressure Liquid Brain Neoplasms Rats Inbred Strains General Medicine Isoquinolines Receptors GABA-A medicine.disease Ligand (biochemistry) Rats chemistry Specific activity Tomography Emission-Computed |
| Zdroj: | International Journal of Radiation Applications and Instrumentation. Part B. Nuclear Medicine and Biology. 16:423-429 |
| ISSN: | 0883-2897 |
| DOI: | 10.1016/0883-2897(89)90111-6 |
| Popis: | The peripheral benzodiazepine binding site ligand PK 11195 has been 125 I-labeled by direct displacement of aromatic chlorine under solid-state conditions in 50–76% radiochemical yield and >94% radiochemical purity. Purification by high pressure liquid chromatography increased the specific activity of the product from an initial 15–17 Ci/mmol to a final activity of 260–910 Ci/mmol. To determine the affinity of this [ 125 I]PK 11195 analog for human glioma cells, saturation experiments were performed on monolayers of U 251 human glioblastoma cells. Scatchard analysis of saturation data demonstrated that the [ 125 I]PK 11195 analog binds to a single class of sites with a K D of 8.0 ± 1.7 nM and maximal binding of 3.8 ± 0.1 pmol/mg protein. These values are similar to those obtained when [ 3 H]PK 11195 was assayed in U 251 cells ( K D = 14 ± 3.4, B max = 4.1 ± 1.3) suggesting that iodination does not appreciably alter the binding of PK 11195 to human glioma cells. In vivo autoradiographic studies of brain in C 6 glioma bearing rats demonstrate selective binding of the radioligand to the tumor. These results suggest that this [ 125 I]PK 11195 analog may be a useful radiotracer for the study of peripheral benzodiazepine binding sites. |
| Databáze: | OpenAIRE |
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