RT Journal Article
SR Electronic
T1 Tumor Imaging with 2 σ-Receptor Ligands, <sup>18</sup>F-FE-SA5845 and <sup>11</sup>C-SA4503: A Feasibility Study
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1939
OP 1945
VO 45
IS 11
A1 Aren van Waarde
A1 Anne Rixt Buursma
A1 Geke A.P. Hospers
A1 Kazunori Kawamura
A1 Tadayuki Kobayashi
A1 Kenji Ishii
A1 Keiichi Oda
A1 Kiichi Ishiwata
A1 Willem Vaalburg
A1 Philip H. Elsinga
YR 2004
UL http://jnm.snmjournals.org/content/45/11/1939.abstract
AB Our objective was to study 2 radioligands for visualization of σ-receptors with PET. Methods: Two radioligands—σ1-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 tumor-to-muscle ratios of 5.0 for 11C-SA4503 and 4.9 for 18F-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 μmol/kg). Tumor uptake of 18F-FE-SA5845 showed a negative correlation with tumor size (P &lt; 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 11C-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 11C-SA4503 demonstrate specific binding to σ-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.