Tumor imaging with 2 sigma-receptor ligands, 18F-FE-SA5845 and 11C-SA4503: a feasibility study

Our objective was to study 2 radioligands for visualization of sigma-receptors with PET.

Two radioligands-sigma(1)-selective (11)C-1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ((11)C-SA4503) and nonsubtype-selective 1-(4-2'-(18)F-fluoroethoxy-3-methoxyphenethyl)-4-(3-(4-fluorophenyl)propyl)piperazine ((18)F-FE-SA5845)-were evaluated for tumor imaging.

Binding studies to rat glioma cells (C6) and human nonsmall cell lung cancer cells (N417) indicated interaction of (18)F-FE-SA5845 with 2 sites and interaction of (11)C-SA4503 with a single site. Specific binding of (18)F-FE-SA5845 was 93% +/- 2% and that of (11)C-SA4503 was 78% +/- 6% of the total cellular uptake of radioactivity. Uptake of the (18)F-labeled ligand, but not that of the (11)C-labeled ligand, appeared to be related to the growth phase of the cells. Biodistribution experiments in C6 tumor-bearing nude rats (Ham HSD RNU rnu) indicated tumor-to-plasma ratios of 13.3 for (11)C-SA4503 and 8.0 for (18)F-FE-SA5845 and tumor-to-muscle ratios of 5.0 for (11)C-SA4503 and 4.9 for (18)F-FE-SA5845, 60 min after injection, which were reduced to values ranging from 1.4 to 2.0 after pretreatment of animals with haloperidol (2 micromol/kg). Tumor uptake of (18)F-FE-SA5845 showed a negative correlation with tumor size (P < 0.0001), in contrast to that of (11)C-SA4503, suggesting that tissue binding of the former ligand is related to cellular proliferation. A study with (11)C-SA4503 in a human volunteer indicated high uptake in liver, kidney, and heart but relatively low background in thorax and lower abdomen.

Both (18)F-FE-SA5845 and (11)C-SA4503 demonstrate specific binding to sigma-receptors in vivo and may be useful for the detection of pulmonary and abdominal tumors. However, the (18)F-labeled compound may be better for tumor staging than the (11)C-labeled drug.