Synthesis and biological evaluation of a radioiodinated spiropiperidine ligand as a potential σ1 receptor imaging agent


Synthesis and biological evaluation of a radioiodinated spiropiperidine ligand as a potential σ1 receptor imaging agent

Chen, R.-Q.; Li, Y.; Zhang, Q.-Y.; Jia, H.-M.; Deuther-Conrad, W.; Schepmann, D.; Steinbach, J.; Brust, P.; Wuensch, B.; Liu, B.-L.

We report the synthesis and evaluation of 1'-(4-[125I]iodobenzyl)-3H-spiro[isobenzofuran-1,4'-piperidine] ([125I]Spiro-I) as a potential SPECT tracer for imaging of σ1 receptors. [125I]Spiro-I was prepared in 55–65% isolated radiochemical yield, with radiochemical purity of >99%, via iododestannylation of the corresponding tributyltin precursor. In receptor binding studies, Spiro-I displayed low nanomolar affinity for σ1 receptors (σ1: Ki = 2.75 ± 0.12 nM; σ2: Ki = 340 nM) and high subtype selectivity (σ2/σ1 = 124). Biodistribution in mice demonstrated relatively high concentration of radioactivity in organs known to contain σ1 receptors, including the lung, kidney, heart, spleen, and brain. Administration of haloperidol 5 min prior to injection of [125I]Spiro-I significantly reduced the concentration of radioactivity in the above-mentioned organs. These findings suggest that the binding of [125I]Spiro-I to σ1 receptors in vivo is specific.

Keywords: σ1 receptor; spiropiperidine; Iodine-125

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Publ.-Id: 14276