Gd³⁺-DTPA-DG: novel nanosized dual anticancer and molecular imaging agent

Massoud Amanlou¹, Seyed Davar Siadat^4,5, Seyed Esmaeil Sadat Ebrahimi¹, Abass Alavi⁷, Mohammad Reza Aghasadeghi², Mehdi Shafiee Ardestani^1,4,6*, Saeed Shanehsaz², Masoud Ghorbani⁶, Bita Mehravi⁸, Mohammad Shafiee Alavidjeh³, Ali Jabbari-Arabzadeh¹, Mehdi Abbasi^4
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