Technetium glucose complexes as potential cancer imaging agents

• Published in: Bioorganic & medicinal chemistry letters 2015-10, Vol.25 (19), p.4254-4259
• Main Authors: Dapueto, Rosina, Aguiar, Rodrigo B., Moreno, María, Machado, Camila M.L., Marques, Fabio L.N., Gambini, Juan P., Chammas, Roger, Cabral, Pablo, Porcal, Williams
• Format: Article
• Language: English
• Subjects: 18F-FDG; Animals; Cancer imaging agents; Cell Line, Tumor; Glucose - chemistry; Glucose - pharmacokinetics; Glucose complexes; Melanoma; Melanoma, Experimental - diagnosis; Mice; Mice, Inbred C57BL; Molecular Structure; Organotechnetium Compounds - analysis; Organotechnetium Compounds - chemical synthesis; Organotechnetium Compounds - chemistry; Organotechnetium Compounds - pharmacokinetics; Technetium; Tissue Distribution
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2015.07.098

[Display omitted] GLUT’s (facilitative glucose transporters) over-expression in tumor cells has allowed the detection of several cancer types, using a glucose analogue (18F-FDG) with PET images, worldwide. New glucose analogs radiolabeled with 99mTc could be a less-expensive and more accessible alternative for diagnosis using SPECT imaging. d-Glucose (99mTc-IDAG) and 2-d-deoxyglucose (99mTc-AADG) organometallic complexes were proposed and studied as potential 18F-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 99mTc. 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 18F-FDG in order to compare the uptake of 99mTc-glucose complexes in the tumor model. IDAG and AADG compounds were synthesized and radiolabeled with 99mTcO4− to obtain the 99mTc-IDAG and 99mTc-AADG complexes in high yield and stability. In vitro cell studies showed maximum uptake at 60min for complexes, 99mTc-IDAG and 99mTc-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 99mTc-IDAG and 99mTc-AADG, respectively. SPECT and micro-SPECT-CT images acquired after the injection of 99mTc-IDAG showed accumulation in tumor sites, suggesting that this glucose complex would be a promising candidate for cancer imaging.