title: Evaluation of [11C]SA5845 and [11C]SA4503 for imaging of sigma receptors in tumors by animal PET.
abstract: Sigma receptors are expressed in a wide variety of tumor cell lines, and are expressed in proliferating cells. A radioligand for the visualization of sigma receptors could be useful for selective detection of primary tumors and their metastases, and for non-invasive assessment of tumor proliferative status. To this end we evaluated two sigma receptor ligands, [11C]SA5845 and [11C]SA4503. In an in vitro study, AH109A hepatoma showed moderate densities of sigma1 and sigma2 receptors, and VX-2 carcinoma showed a high density of sigma2 receptors: Bmax (fmol/mg protein) for sigma1 vs. sigma2, 1,700 vs. 1,200 for AH109A hepatoma and 800 vs. 10,000 for VX-2 carcinoma. In a cell growth assay in vitro, neither SA5845 nor SA4503 (<10 microM) showed any inhibitory effect on proliferation of the AH109A hepatoma cells. In rats, the uptake of [11C]SA5845 and [11C]SA4503 in AH109A tissues was accumulated over the first 60 minutes; however, the uptake of both tracers increased by co-injection with haloperidol as a sigma receptor ligand. On the other hand, in the PET studies of rabbits, the uptake of [11C]SA5845 in the VX-2 carcinoma was relatively higher than that of [11C]SA4503, because of a much higher density of sigma2 receptors compared to sigma1 receptors in the VX-2 tissue, and the uptake of both tracers in the VX-2 tissue was decreased by carrier-loading and pre-treatment with haloperidol ([11C]SA5845, 53% and 26%, respectively; [11C]SA4503, 41% and 22%, respectively at 30 minutes after injection). Therefore, [11C]SA5845 and [11C]SA4503 may be potential ligands for PET imaging of sigma receptor-rich tumors.
authors.affiliation: Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Naka-cho 1-1, Itabashi-ku, Tokyo 173-0022, Japan. kawamurak@bri.niigata-u.ac.jp
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kawamura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kubota
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Philip H
authors.initials: PH
authors.lastname: Elsinga
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ono
authors.forename: Minoru
authors.initials: M
authors.lastname: Maeda
authors.forename: Kiichi
authors.initials: K
authors.lastname: Ishiwata
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002277:Carcinoma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D008297:Male; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D010879:Piperazines / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods; D011817:Rabbits; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017480:Receptors, sigma / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D014408:Biomarkers, Tumor; D002250:Carbon Radioisotopes; D010879:Piperazines; D019275:Radiopharmaceuticals; D017480:Receptors, sigma; C509480:SA5845; C101789:SA 4503