Iljung Lee1, Brian P Lieberman1, Shihong Li1, Catherine Hou1, Mehran Makvandi1, Robert H Mach2. 1. Department of Radiology/Nuclear Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19014, USA. 2. Department of Radiology/Nuclear Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19014, USA. Electronic address: rmach@mail.med.upenn.edu.
Abstract
INTRODUCTION: 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 σ2 receptors relative to sigma-1 (σ1) receptors. METHODS: ([18F]7) was synthesized and evaluated as a candidate ligand for positron emission (PET) imaging of the σ2 receptor in tumors. Radioligand [18F]7 was radiolabeled with 18F 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 σ2 receptor status of solid tumors.
INTRODUCTION: 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 σ2 receptors relative to sigma-1 (σ1) receptors. METHODS: ([18F]7) was synthesized and evaluated as a candidate ligand for positron emission (PET) imaging of the σ2 receptor in tumors. Radioligand [18F]7 was radiolabeled with 18F 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 σ2 receptor status of solid tumors.
Authors: Pierpaolo Cordone; Hari K Namballa; Bryant Muniz; Rajat K Pal; Emilio Gallicchio; Wayne W Harding Journal: Bioorg Med Chem Lett Date: 2021-04-18 Impact factor: 2.940