Tumor Imaging with 2 - Receptor Ligands , 18 F - FE - SA 5845 and 11 C - SA 4503 : A Feasibility Study

Our objective was to study 2 radioligands for visualization of -receptors with PET. Methods: Two radioligands— 1-selective 11C-1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine (11C-SA4503) and nonsubtype-selective 1-(4–2 -18F-fluoroethoxy-3-methoxyphenethyl)-4-(3-(4-fluorophenyl)propyl)piperazine (18F-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 11C-SA4503 with a single site. Specific binding of 18F-FE-SA5845 was 93% 2% and that of 11C-SA4503 was 78% 6% of the total cellular uptake of radioactivity. Uptake of the 18F-labeled ligand, but not that of the 11C-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 11C-SA4503 and 8.0 for 18F-FE-SA5845 and tumorto-muscle ratios of 5.0 for 11C-SA4503 and 4.9 for 18F-FESA5845, 60 min after injection, which were reduced to values ranging from 1.4 to 2.0 after pretreatment of animals with haloperidol (2 mol/kg). Tumor uptake of 18F-FE-SA5845 showed a negative correlation with tumor size (P 0.0001), in contrast to that of 11C-SA4503, suggesting that tissue binding of the former ligand is related to cellular proliferation. A study with 11CSA4503 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 11CSA4503 demonstrate specific binding to -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 11C-labeled drug.