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Träfflista för sökning "WFRF:(Jahan M) srt2:(2015-2019)"

Sökning: WFRF:(Jahan M) > (2015-2019)

  • Resultat 1-9 av 9
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1.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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  • Eriksson, Olof, et al. (författare)
  • In Vivo Visualization of beta-Cells by Targeting of GPR44
  • 2018
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 67:2, s. 182-192
  • Tidskriftsartikel (refereegranskat)abstract
    • GPR44 expression has recently been described as highly beta-cell selective in the human pancreas and constitutes a tentative surrogate imaging biomarker in diabetes. A radiolabeled small-molecule GPR44 antagonist, [C-11]AZ12204657, was evaluated for visualization of beta-cells in pigs and non-human primates by positron emission tomography as well as in immunodeficient mice transplanted with human islets under the kidney capsule. In vitro autoradiography of human and animal pancreatic sections from subjects without and with diabetes, in combination with insulin staining, was performed to assess beta-cell selectivity of the radiotracer. Proof of principle of in vivo targeting of human islets by [C-11]AZ12204657 was shown in the immunodeficient mouse transplantation model. Furthermore, [C-11]AZ12204657 bound by a GPR44-mediated mechanism in pancreatic sections from humans and pigs without diabetes, but not those with diabetes. In vivo [C-11]AZ12204657 bound specifically to GPR44 in pancreas and spleen and could be competed away dose-dependently in nondiabetic pigs and nonhuman primates. [C-11]AZ12204657 is a first-in-class surrogate imaging biomarker for pancreatic beta-cells by targeting the protein GPR44.
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4.
  • Jahan, M., et al. (författare)
  • Synthesis and biological evaluation of [C-11]AZ12504948; a novel tracer for imaging of glucokinase in pancreas and liver
  • 2015
  • Ingår i: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 42:4, s. 387-394
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Glucokinase (GK) is potentially a target for imaging of islets of Langerhans. Here we report the radiosynthesis and preclinical evaluation of the GK activator, [C-11]AZ12504948, for in vivo imaging of GK. Methods: [C-11]AZ12504948 was synthesized by O-methylation of the precursor, AZ125555620, using carbon-11 methyl iodide ([C-11]CH3I).Preclinical evaluation was performed by autoradiography (ARC) of human tissues and PET/CT studies in pig and non-human primate. Result: [C-11]AZ12504948 was produced in reproducible good radiochemical yield in 28-30 min. Radiochemical purity of the formulated product was >98% for up to 2 h with specific radioactivities 855 +/- 209 GBq/mu mol (n = 8). The preclinical evaluation showed some specificity for GK in liver, but not in pancreas. Conclusion:[C-11]AZ12504948 images GK in liver, but the low specificity impedes the visualization of GK in pancreas. Improved target specificity is required for further progress using PET probes based on this class of GK activators.
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