Evaluation of [11C]SA5845 and [11C]SA4503 for imaging of sigma receptors in tumors by animal PET.

Sigma receptors are expressed in a wide variety of tumor cell lines, and are expressed in proliferating cells. A radioligand for the visualization of sigma receptors could be useful for selective detection of primary tumors and their metastases, and for non-invasive assessment of tumor proliferative status. To this end we evaluated two sigma receptor ligands, [11C]SA5845 and [11C]SA4503. In an in vitro study, AH109A hepatoma showed moderate densities of sigma1 and sigma2 receptors, and VX-2 carcinoma showed a high density of sigma2 receptors: Bmax (fmol/mg protein) for sigma1 vs. sigma2, 1,700 vs. 1,200 for AH109A hepatoma and 800 vs. 10,000 for VX-2 carcinoma. In a cell growth assay in vitro, neither SA5845 nor SA4503 (<10 microM) showed any inhibitory effect on proliferation of the AH109A hepatoma cells. In rats, the uptake of [11C]SA5845 and [11C]SA4503 in AH109A tissues was accumulated over the first 60 minutes; however, the uptake of both tracers increased by co-injection with haloperidol as a sigma receptor ligand. On the other hand, in the PET studies of rabbits, the uptake of [11C]SA5845 in the VX-2 carcinoma was relatively higher than that of [11C]SA4503, because of a much higher density of sigma2 receptors compared to sigma1 receptors in the VX-2 tissue, and the uptake of both tracers in the VX-2 tissue was decreased by carrier-loading and pre-treatment with haloperidol ([11C]SA5845, 53% and 26%, respectively; [11C]SA4503, 41% and 22%, respectively at 30 minutes after injection). Therefore, [11C]SA5845 and [11C]SA4503 may be potential ligands for PET imaging of sigma receptor-rich tumors.