title: Synthesis, characterization and biodistribution of neutral and lipid-soluble 99mTc-bisaminoethanethiol spiperone derivatives: possible ligands for receptor imaging with SPECT.
abstract: Using parts of the molecular structure of spiperone, two new ligand systems for complexation with [99mTc]technetium were prepared in order to develop potential receptor imaging agents for single photon emission computer tomography (SPECT). The bis-aminoethanethiols (BAT): 1-benzyl-4-(2-mercapto-2-methyl-4-aza-pentyl)-4-(2-mercapto-2-methyl- propylamino)-piperidine (benzylpiperidyl-BAT, BP-BAT) and 1-[3-(4-fluorobenzoyl)-propyl]-4-(2-mercapto-2-methyl-4-aza-pentyl)-4- (2-mercapto-2-methyl-propyl-amino)-piperidine (butyrophenoylpiperidyl-BAT, BUP-BAT) form stable, neutral and lipid soluble complexes with [99mTc]technetium at pH > or = 11 using SnCl2 as reducing agent in nearly quantitative radiochemical yields. Biodistribution of 99mTc-BP-BAT and 99mTc-BUP-BAT in rats showed a moderate clearance from blood and low uptake and retention in the liver, whereas brain uptake was moderate, however with prolonged brain retention. On the other hand, significant accumulations and retentions were observed in heart, kidney and lung with increasing oxygen/blood ratios up to 24 h. Within 24 h p.i. 22 and 29% of the injected dose (i.d.) of 99mTc-BP-BAT and 99mTc-BUP-BAT were eliminated by hepatobiliary excretion whereas 22% i.d. of both 99mTc-BAT complexes were excreted into the urine. Although first biodistribution studies of 99mTc-BP-BAT and 99mTc-BUP-BAT in rats showed relatively low brain uptake, the high uptake in peripheral, receptor rich organs indicates that compounds of this type may be used as a basis for further structural modification to develop agents with optimal properties for cerebral or peripheral receptor imaging with SPECT.
authors.affiliation: Klinik und Poliklinik für Nuklearmedizin, University of Münster, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Samnick
authors.forename: W
authors.initials: W
authors.lastname: Brandau
authors.forename: J
authors.initials: J
authors.lastname: Sciuk
authors.forename: A
authors.initials: A
authors.lastname: Steinsträsser
authors.forename: O
authors.initials: O
authors.lastname: Schober
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004591:Electrophoresis, Polyacrylamide Gel; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000737:chemistry; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000378:metabolism*; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013134:Spiperone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D008024:Ligands; D015609:Organotechnetium Compounds; D011954:Receptors, Dopamine; D013134:Spiperone