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.


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.


CONCLUSIONS
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.
van Waarde
Aren
A
PET Center, Groningen University Hospital, 9700 RB Groningen, The Netherlands.
Buursma
Anne Rixt
AR
Hospers
Geke A P
GA
Kawamura
Kazunori
K
Kobayashi
Tadayuki
T
Ishii
Kenji
K
Oda
Keiichi
K
Ishiwata
Kiichi
K
Vaalburg
Willem
W
Elsinga
Philip H
PH
D000368:Aged; D000818:Animals; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D005240:Feasibility Studies; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D010879:Piperazines / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011923:Rats, Nude; D017480:Receptors, sigma / Q000378:metabolism*; D014018:Tissue Distribution
C494899:1-(4-2'-fluoroethoxy-3-methoxyphenethyl)-4-(3-(4-fluorophenyl)propyl)piperazine; D002250:Carbon Radioisotopes; D010879:Piperazines; D019275:Radiopharmaceuticals; D017480:Receptors, sigma; C101789:SA 4503