title: Comparative evaluation of 4 and 6-carbon spacer conformationally flexible tetrahydroisoquinolinyl benzamide analogues for imaging the sigma-2 receptor status of solid tumors.
abstract: BACKGROUND
  Nine novel analogues were synthesized including a 6-carbon spacer analogue of ISO-1 (7). They have moderate binding affinity for sigma-2 (σ2) receptors and high selectivity for σ2receptors relative to sigma-1 (σ1) receptors.
  
  
  METHODS
  ([18F]7) was synthesized and evaluated as a candidate ligand for positron emission (PET) imaging of the σ2receptor in tumors. Radioligand [18F]7 was radiolabeled with18F via displacement of the corresponding mesylate precursor with [18F]fluoride. Cellular uptake study of [18F]7 was performed in EMT-6 tumor cell, and in vivo biodistribution study of [18F]7 and microPET imaging study of [18F]3 and [18F]7 carried out in female Balb/c mice bearing EMT-6 tumors.
  
  
  RESULTS
  [18F]7 had a respectable tumor uptake (1.55%ID/g at 60min post-injection) and high tumor/muscle ratios at 60 and 120min post-injection. MicroPET imaging of [18F]7 in tumor-bearing mice as above showed significant tumor localization and a high tumor/muscle ratio as well.
  
  
  CONCLUSIONS
  These results are similar to or better than [18F]ISO-1 ([18F]3), which indicates that [18F]7 has potential for imaging the σ2receptor status of solid tumors.
authors: Department of Radiology/Nuclear Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19014, USA.
authors: Iljung
authors: I
authors: Lee
authors: Department of Radiology/Nuclear Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19014, USA.
authors: Brian P
authors: BP
authors: Lieberman
authors: Department of Radiology/Nuclear Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19014, USA.
authors: Shihong
authors: S
authors: Li
authors: Department of Radiology/Nuclear Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19014, USA.
authors: Catherine
authors: C
authors: Hou
authors: Department of Radiology/Nuclear Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19014, USA.
authors: Mehran
authors: M
authors: Makvandi
authors: Department of Radiology/Nuclear Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19014, USA. Electronic address: rmach@mail.med.upenn.edu.
authors: Robert H
authors: RH
authors: Mach
mesh_terms: D000818:Animals; D001549:Benzamides / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D001692:Biological Transport; D002244:Carbon / Q000737:chemistry*; D045744:Cell Line, Tumor; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging*; D051379:Mice; D008968:Molecular Conformation; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry; D017480:Receptors, sigma / Q000378:metabolism*; D044005:Tetrahydroisoquinolines / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D001549:Benzamides; D017480:Receptors, sigma; D044005:Tetrahydroisoquinolines; C106107:sigma-2 receptor; C014843:1,2,3,4-tetrahydroisoquinoline; D002244:Carbon
keywords: EMT-6 cells; PET; Sigma-2 receptors; Tumor cell proliferation; Tumor imaging