Gd3+-DTPA-DG: novel nanosized dual anticancer and molecular imaging agent
Massoud Amanlou1, Seyed Davar Siadat4,5, Seyed Esmaeil Sadat Ebrahimi1, Abass Alavi7, Mohammad Reza Aghasadeghi2, Mehdi Shafiee Ardestani1,4,6*, Saeed Shanehsaz2, Masoud Ghorbani6, Bita Mehravi8, Mohammad Shafiee Alavidjeh3, Ali Jabbari-Arabzadeh1, Mehdi Abbasi4
1Department of Medicinal Chemistry, Faculty of Pharmacy; 2Department of Medical Physics, School of Medicine; 3Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 4Department of Hepatitis and AIDS; 5Department of Microbiology; 6R&D & QC & Hepatitis B & Nanobiotechnology Department, Research and Production Complex, Pasteur Institute of Iran, Tehran, Iran; 7Department of Radiology, Division of Nuclear Medicine, School of Medicine, Pennsylvania University of Medical Sciences, Philadelphia, PA, USA; 8Department of Nanomedicine, Shahid Beheshti Medical University, Tehran, Iran
Background: Difficulties in the use, preparation, and cost of radioactively-labeled glycosylated compounds led to this research and development study of a new gadolinium-labeled glucose compound that does not have a radioactive half-life or difficulties in its synthesis and utilization.
Methods: Based on the structure of the 2-fluoro-2-deoxy-D-glucose molecule (18FDG), a new compound consisting of D-glucose (1.1 nm) conjugated to a well-known chelator, diethylenetriamine penta-acetic acid (DTPA), was synthesized, labeled with Gd3+, and examined in vitro and in vivo.
Results: This novel compound not only demonstrated excellent and less costly imaging capability, but also showed anticancer effects on treated cells. Our results demonstrated that the new Gd3+-DTPA-DG compound (GDD, with GDD conjugate aggregation of about 8 nm at 0.02 mg/mL concentration) significantly decreased HT1080 and HT29 tumor cell numbers. Application of GDD to cancer cells also increased levels of tumor necrosis factor alpha, but did not alter blood glucose levels. Interestingly, no toxicological findings were seen in normal human kidney cells.
Conclusion: Dual application of GDD for both imaging and treatment of tumor cells could be remarkably advantageous in both the diagnosis and treatment of cancer.
Keywords: fluorodeoxyglucose, Gd3+-DTPA-DG, positron emission tomography, diagnostics, treatment