title: Novel mixed ligand technetium complexes as 5-HT1A receptor imaging agents.
abstract: The synthesis, characterization and biological evaluation of two novel 3 + 1 mixed ligand 99mTc-complexes, bearing the 1-(2-methoxyphenylpiperazine) moiety, a fragment of the true 5-HT1A antagonist WAY 100635, is reported. Complexes at tracer level 99mTcO[(CH3CH2)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N(CH2CH2)2NCH2CH2S], 99mTc-1, and 99mTcO[((CH3)2CH)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N (CH2CH2)2NCH2CH2S], 99mTc-2, were prepared using 99mTc-glucoheptonate as precursor. For structural characterization, the analogous oxorhenium complexes, Re-1 and Re-2, were prepared by ligand exchange reaction using ReOCl3(PPh3)2 as precursor, and characterized by elemental analysis and spectroscopic methods. Complex Re-1 was further characterized by crystallographic analysis. Labeling was performed with high yield (>85%) and radiochemical purity (>90%) using very low ligand concentration. The structure of 99mTc complexes was established by comparative HPLC using the well-characterized oxorhenium analogues as references. In vitro binding assays demonstrated the affinity of these complexes for 5-HT1A receptors (IC50 : 67 and 45 nM for Re-1 and Re-2 respectively). Biological studies in mice showed the ability of 99mTc-1 and 99mTc-2 complexes to cross the intact blood-brain barrier (1.4 and 0.9% dose/g, respectively at 1 min post-inj.). The distribution of these complexes in various regions in rat brain is inhomogeneous. The highest ratio between areas reach and poor in 5-HT1A receptors was calculated for complex Tc-1 at 60 min p.i. (hippocampus/cerebellum = 1.7).
authors.affiliation: Cátedras de Radioquímica y Química Farmacéutica, Facultad de Química, C.C. 1157, Montevideo, Uruguay.
authors.forename: A
authors.initials: A
authors.lastname: León
authors.forename: A
authors.initials: A
authors.lastname: Rey
authors.forename: L
authors.initials: L
authors.lastname: Mallo
authors.forename: I
authors.initials: I
authors.lastname: Pirmettis
authors.forename: M
authors.initials: M
authors.lastname: Papadopoulos
authors.forename: E
authors.initials: E
authors.lastname: León
authors.forename: M
authors.initials: M
authors.lastname: Pagano
authors.forename: E
authors.initials: E
authors.lastname: Manta
authors.forename: M
authors.initials: M
authors.lastname: Incerti
authors.forename: C
authors.initials: C
authors.lastname: Raptopoulou
authors.forename: A
authors.initials: A
authors.lastname: Terzis
authors.forename: E
authors.initials: E
authors.lastname: Chiotellis
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008024:Ligands; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D009942:Organometallic Compounds / Q000032:analysis / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000032:analysis / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011869:Radioligand Assay; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012211:Rhenium / Q000737:chemistry
chemical_list: D008024:Ligands; D009942:Organometallic Compounds; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012211:Rhenium