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Titolo:
Development of a Tc-99m labeled sigma-2 receptor-specific ligand as a potential breast tumor imaging agent
Autore:
Choi, SR; Yang, B; Plossl, K; Chumpradit, S; Wey, SP; Acton, PD; Wheeler, K; Mach, RH; Kung, HF;
Indirizzi:
Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA Univ Penn PhiladelphiaPA USA 19104 pt Radiol, Philadelphia, PA 19104 USA Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 Pharmacol, Philadelphia, PA 19104 USA Wake Forest Univ, Sch Med, Dept Radiol, Winston Salem, NC 27157 USA Wake Forest Univ Winston Salem NC USA 27157 , Winston Salem, NC 27157 USA Wake Forest Univ, Sch Med, Dept Physiol, Winston Salem, NC 27157 USA Wake Forest Univ Winston Salem NC USA 27157 , Winston Salem, NC 27157 USA Wake Forest Univ, Sch Med, Dept Pharmacol, Winston Salem, NC 27157 USA Wake Forest Univ Winston Salem NC USA 27157 , Winston Salem, NC 27157 USA Anasazi BioMed Res Inc, Winston Salem, NC 27101 USA Anasazi BioMed Res Inc Winston Salem NC USA 27101 ton Salem, NC 27101 USA
Titolo Testata:
NUCLEAR MEDICINE AND BIOLOGY
fascicolo: 6, volume: 28, anno: 2001,
pagine: 657 - 666
SICI:
0969-8051(200108)28:6<657:DOATLS>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
IN-VIVO EVALUATION; BINDING-SITES; PET; CELLS; RAT; PROLIFERATION; RADIOLIGAND; BENZAMIDES; TECHNETIUM; MODULATION;
Keywords:
tumor imaging agents; receptors; Tc-99m; SPECT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Kung, HF Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 , Philadelphia, PA 19104 USA
Citazione:
S.R. Choi et al., "Development of a Tc-99m labeled sigma-2 receptor-specific ligand as a potential breast tumor imaging agent", NUCL MED BI, 28(6), 2001, pp. 657-666

Abstract

A novel in vivo imaging agent, Tc-99m labeled [(N-[2-((3'-N'-propyl-[3,3.1]aza-bicyclononan-3 alpha -yl)(2"-methoxy-5-methyl-phenylcarbamate)(2-mercaptoethyl)amino)acetyl]-2-aminoethanethiolato] technetium(V) oxide), [Tc-99m]2, displaying specific binding towards sigma-2 receptors was prepared and characterized. In vitro binding assays showed that the rhenium, surrogate of [Tc-99m]2, Re-2, displayed excellent binding affinity and selectivity towards sigma-2 receptors (K-i = 2,723 and 22 nM for sigma-1 and sigma-2 receptor, respectively). Preparation of [Tc-99m]2 was achieved by heating the S-protected starting material, 1, in the presence of acid, reducing agent (stannous glucoheptonate) and sodium [Tc-99m]pertechnetate. The lipophilic racemic mixture was successfully prepared in 10 to 50% yield and the radiochemical purity was >98%. Separation of the isomers, peak A and peak B, was successfully achieved by using a chiralpak AD column eluted with an isocratic solvent (n-hexane/isopropanol; 3: 1; v/v). The peak A and peak B appear to co-elute with the isomers of the surrogate, Re-2, under the same HPLC condition. Biodistribution studies in tumor bearing mice (mouse mammary adenocarcinoma, cell line 66, which is known to over-express sigma-2 receptors) showed that the racemic [Tc-99m]2 localized in the tumor. Uptake in the tumor was 2.11, 1.30 and 1.11 %dose/gram at 1, 4 and 8 hr post iv injection. respectively, suggesting good uptake and retention in the tumor cells. The tumor uptake was significantly, but incompletely, blocked (about 25-30% blockage) by co-injection of "cold" (+)pentazocine or haloperidol (1 mg/Kg). A majority of the radioactivity localized in the tumor tissue was extractable (>60%), and the HPLC analysis showed that it is the original compound, racemic [Tc-99m]2 (>98% pure). The distribution of the purified peak A and peak Bwas determined in the same tumor bearing mice at 4 hr post iv injection. The tumor uptake was similar for both isomers, but the blood and peripheral tissue content for the isomer in peak B was higher than that for the isomerin peak A. It is evident that the isomer in peak A displayed significantlybetter tumor/blood and tumor/muscle ratios. The higher rate of in vivo metabolism was also confirmed by the higher thyroid uptake values for the isomer in peak B as compared to peak A. in summary, a Tc-99m-labeled sigma receptor imaging agent. [Tc-99m]2, has demonstrated the feasibility of using a Tc-99m-labeled agent for imaging sigma receptor expression in tumor cells. This is the first time a subtype-selective Tc-99m-labeled agent for imagingsigma receptor sites is reported. (C) 2001 Elsevier Science Inc. All rights reserved.

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Documento generato il 17/09/19 alle ore 23:01:52