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

Abstract

UNLABELLED:

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

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: Aren van Waarde, Anne Rixt Buursma, Geke A P Hospers, Kazunori Kawamura, Tadayuki Kobayashi, Kenji Ishii, Keiichi Oda, Kiichi Ishiwata, Willem Vaalburg, Philip H Elsinga
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 45 Issue 11 Pg. 1939-45 (Nov 2004) ISSN: 0161-5505 [Print] United States
• PMID: 15534066 (Publication Type: Case Reports, Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1-(4-2'-fluoroethoxy-3-methoxyphenethyl)-4-(3-(4-fluorophenyl)propyl)piperazine
• Carbon Radioisotopes
• Piperazines
• Radiopharmaceuticals
• Receptors, sigma
• SA 4503

Topics

• Aged
• Animals
• Carbon Radioisotopes (pharmacokinetics)
• Cell Line, Tumor
• Feasibility Studies
• Female
• Glioma (diagnostic imaging, metabolism)
• Humans
• Metabolic Clearance Rate
• Organ Specificity
• Piperazines (pharmacokinetics)
• Radionuclide Imaging
• Radiopharmaceuticals (pharmacokinetics)
• Rats
• Rats, Nude
• Receptors, sigma (metabolism)
• Tissue Distribution