title: Technetium glucose complexes as potential cancer imaging agents.
abstract: GLUT's (facilitative glucose transporters) over-expression in tumor cells has allowed the detection of several cancer types, using a glucose analogue ((18)F-FDG) with PET images, worldwide. New glucose analogs radiolabeled with (99m)Tc could be a less-expensive and more accessible alternative for diagnosis using SPECT imaging. d-Glucose ((99m)Tc-IDAG) and 2-d-deoxyglucose ((99m)Tc-AADG) organometallic complexes were proposed and studied as potential (18)F-FDG surrogates. The glucose complexes were prepared and evaluated as potential cancer imaging agents, in a melanoma tumor model. Iminodiacetic acid (IDA) and aminoacetate (AA) moieties were chosen as chelating system for radiolabeling with (99m)Tc. Tumor uptake of the formed complexes was evaluated in B16 murine cell line in vitro and in vivo in melanoma bearing C57BL/6 mice. In vitro and in vivo studies were conducted with (18)F-FDG in order to compare the uptake of (99m)Tc-glucose complexes in the tumor model. IDAG and AADG compounds were synthesized and radiolabeled with (99m)TcO4(-) to obtain the (99m)Tc-IDAG and (99m)Tc-AADG complexes in high yield and stability. In vitro cell studies showed maximum uptake at 60 min for complexes, (99m)Tc-IDAG and (99m)Tc-AADG, with 6% and 2%, respectively. Biodistribution studies showed high tumor uptake one hour post-injection, reaching tumor-to-muscle ratios of 12.1 ± 3.73 and 2.88 ± 1.40 for (99m)Tc-IDAG and (99m)Tc-AADG, respectively. SPECT and micro-SPECT-CT images acquired after the injection of (99m)Tc-IDAG showed accumulation in tumor sites, suggesting that this glucose complex would be a promising candidate for cancer imaging.
authors: Laboratorio de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo, Uruguay; Grupo de Química Medicinal, Laboratorio de Química Orgánica, Facultad de Ciencias-Facultad de Química, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay.
authors: Rosina
authors: R
authors: Dapueto
authors: Centro de Investigação Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo, Av. Dr. Arnaldo, 251, São Paulo 01246-903, Brazil.
authors: Rodrigo B
authors: RB
authors: Aguiar
authors: Departamento de Desarrollo Biotecnológico, Instituto de Higiene, Facultad de Medicina, Universidad de la Republica, Av. Alfredo Navarro 3051, 11600 Montevideo, Uruguay.
authors: María
authors: M
authors: Moreno
authors: Centro de Medicina Nuclear, Faculdade de Medicina, Universidade de São Paulo, Trav. R. Dr. Ovidio Pires de Campos s/n, São Paulo 05403-010, Brazil.
authors: Camila M L
authors: CM
authors: Machado
authors: Centro de Medicina Nuclear, Faculdade de Medicina, Universidade de São Paulo, Trav. R. Dr. Ovidio Pires de Campos s/n, São Paulo 05403-010, Brazil.
authors: Fabio L N
authors: FL
authors: Marques
authors: Centro de Medicina Nuclear, Hospital de Clínicas, Facultad de Medicina, Universidad de la Republica, Av Italia s/n, 11600 Montevideo, Uruguay.
authors: Juan P
authors: JP
authors: Gambini
authors: Centro de Investigação Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo, Av. Dr. Arnaldo, 251, São Paulo 01246-903, Brazil.
authors: Roger
authors: R
authors: Chammas
authors: Laboratorio de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo, Uruguay. Electronic address: pcabral@cin.edu.uy.
authors: Pablo
authors: P
authors: Cabral
authors: Grupo de Química Medicinal, Laboratorio de Química Orgánica, Facultad de Ciencias-Facultad de Química, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay. Electronic address: wporcal@fq.edu.uy.
authors: Williams
authors: W
authors: Porcal
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005947:Glucose / Q000737:chemistry* / Q000493:pharmacokinetics*; D008546:Melanoma, Experimental / Q000175:diagnosis*; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D015609:Organotechnetium Compounds / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D015609:Organotechnetium Compounds; D005947:Glucose
keywords: (18)F-FDG; Cancer imaging agents; Glucose complexes; Melanoma; Technetium