title: Design and development of (99m)tc-'4+1'-labeled dextran-mannose derivatives as potential radiopharmaceuticals for sentinel lymph node detection.
abstract: The synthesis, labeling, and biological evaluation of a dextran derivative (DCM-30-iso) as potential radiopharmaceutical for sentinel lymph node imaging is presented. DCM-30-iso bears mannose as active moiety and isocyanide as ligand for technetium through the formation of a '4+1' Tc(III) mixed-ligand complex. A second derivative without mannose (DC-25-iso) was also prepared and evaluated as control. DCM-30-iso and DC-25-iso were synthesized from dextran in four steps (>50% overall yield) and characterized by spectroscopic methods. Labeling with (99m)Tc was achieved by reaction with 2,2',2''-nitrilotris(ethanethiol) and (99m)Tc-EDTA. Radiochemical purity was above 90% and was stable for at least 4 hours postlabeling at 37°C. The identity of the (99m)Tc complex was established through comparative HPLC studies using the well-characterized analogous Re-DC-25-iso complex. Biodistribution and imaging experiments of (99m)Tc-DCM-30-iso showed high uptake in the popliteal lymph node, which could be blocked with preinjection of mannose, and very low uptake in other nodes and organs. The nonmannosylated (99m)Tc-DC-25-iso derivative showed negligible uptake in all lymph nodes. The novel dextran-mannose derivative DCM-30-iso can be successfully labeled with (99m)Tc to give a well-characterized '4+1' complex with favorable biological properties as sentinel lymph node imaging agent.
authors: Cátedra de Radioquímica, Facultad de Química, Universidad de la República, Montevideo, Uruguay.
authors: Javier
authors: J
authors: Giglio
authors: Soledad
authors: S
authors: Fernández
authors: Christian
authors: C
authors: Jentschel
authors: Hans-Jürgen
authors: HJ
authors: Pietzsch
authors: Minas
authors: M
authors: Papadopoulos
authors: Maria
authors: M
authors: Pelecanou
authors: Ioannis
authors: I
authors: Pirmettis
authors: Andrea
authors: A
authors: Paolino
authors: Ana
authors: A
authors: Rey
mesh_terms: D000818:Animals; D003911:Dextrans / Q000737:chemistry*; D015195:Drug Design; D005260:Female; D008358:Mannose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D008958:Models, Molecular; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D021701:Sentinel Lymph Node Biopsy / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D003911:Dextrans; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D008358:Mannose