Dapueto Rosina, Aguiar Rodrigo B, Moreno María, Machado Camila M L, Marques Fabio L N, Gambini Juan P, Chammas Roger, Cabral Pablo, Porcal Williams
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.
Centro de Investigação Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo, Av. Dr. Arnaldo, 251, São Paulo 01246-903, Brazil.
Bioorg Med Chem Lett. 2015 Oct 1;25(19):4254-9. doi: 10.1016/j.bmcl.2015.07.098. Epub 2015 Aug 14.
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.
葡萄糖转运蛋白（GLUT，即易化型葡萄糖转运体）在肿瘤细胞中的过度表达，使得利用葡萄糖类似物（(18)F-FDG）和PET图像在全球范围内检测多种癌症类型成为可能。用(99m)Tc标记的新型葡萄糖类似物可能是一种成本更低且更易于获取的用于SPECT成像诊断的替代物。已提出并研究了d-葡萄糖（(99m)Tc-IDAG）和2-脱氧-d-葡萄糖（(99m)Tc-AADG）有机金属配合物作为潜在的(18)F-FDG替代物。在黑色素瘤肿瘤模型中制备并评估了这些葡萄糖配合物作为潜在的癌症成像剂。选择亚氨基二乙酸（IDA）和氨基乙酸（AA）部分作为与(99m)Tc进行放射性标记的螯合体系。在体外的B16鼠细胞系以及体内荷黑色素瘤的C57BL/6小鼠中评估了所形成配合物的肿瘤摄取情况。为了比较(99m)Tc-葡萄糖配合物在肿瘤模型中的摄取情况，同时进行了(18)F-FDG的体外和体内研究。合成了IDAG和AADG化合物并用(99m)TcO4(-)进行放射性标记，以高产率和稳定性获得(99m)Tc-IDAG和(99m)Tc-AADG配合物。体外细胞研究表明，配合物(99m)Tc-IDAG和(99m)Tc-AADG在60分钟时摄取量最大，分别为6%和2%。生物分布研究表明，注射后一小时肿瘤摄取量较高，(99m)Tc-IDAG和(99m)Tc-AADG的肿瘤与肌肉比值分别达到12.1±3.73和2.88±1.40。注射(99m)Tc-IDAG后获得的SPECT和显微SPECT-CT图像显示在肿瘤部位有聚集，表明这种葡萄糖配合物可能是一种有前景的癌症成像候选物。
