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

Our objective was to study 2 radioligands for visualization of sigma-receptors with PET. Methods: Two radioligands--sigma(1)-selective C-11-1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine (C-11-SA4503) and nonsubtype-selective 1-(4-2'-F-18-fluoroethoxy-3-methoxyphenethyl)-4-(3-(4-fluorophenyl)propyl)piperazine (F-18-FE-SA5845)-were evaluated for tumor imaging. Results: Binding studies to rat glioma cells (C6) and human nonsmall cell lung cancer cells (N417) indicated interaction of 18F-FE-SA5845 with 2 sites and interaction of C-11-SA4503 with a single site. Specific binding of 18F-FE-SA5845 was 93% +/- 2% and that of C-11-SA4503 was 78% +/- 6% of the total cellular uptake of radioactivity. Uptake of the F-18-labeled ligand, but not that of the C-11-labeled ligand, appeared to be related to the growth phase of the cells. Biodistribution experiments in C6 tumor-bearing nude rats (Ham HSD RNU mu) indicated tumor-to-plasma ratios of 13.3 for C-11-SA4503 and 8.0 for F-18-FE-SA5845 and tumorto-muscle ratios of 5.0 for C-11-SA4503 and 4.9 for F-18-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 mumol/kg). Tumor uptake of 18F-FE-SA5845 showed a negative correlation with tumor size (P <0.0001), in contrast to that of C-11-SA4503, suggesting that tissue binding of the former ligand is related to cellular proliferation. A study with C-11-SA4503 in a human volunteer indicated high uptake in liver, kidney, and heart but relatively low background in thorax and lower abdomen. Conclusion: Both 18F-FE-SA5845 and C-11- SA4503 demonstrate specific binding to sigma-receptors in vivo and may be useful for the detection of pulmonary and abdominal tumors. However, the 18F-labeled compound may be better for tumor staging than the C-11-labeled drug.