Comparative evaluation of 4 and 6-carbon spacer conformationally flexible tetrahydroisoquinolinyl benzamide analogues for imaging the sigma-2 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 (σ) receptors and high selectivity for σ receptors relative to sigma-1 (σ) receptors.

Methods: ([F]7) was synthesized and evaluated as a candidate ligand for positron emission (PET) imaging of the σ receptor in tumors. Radioligand [F]7 was radiolabeled with F via displacement of the corresponding mesylate precursor with [F]fluoride. Cellular uptake study of [F]7 was performed in EMT-6 tumor cell, and in vivo biodistribution study of [F]7 and microPET imaging study of [F]3 and [F]7 carried out in female Balb/c mice bearing EMT-6 tumors.

Results: [F]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 [F]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 [F]ISO-1 ([F]3), which indicates that [F]7 has potential for imaging the σ receptor status of solid tumors.