Aim: Neuroblastoma is an aggressive neuroendocrine cancer with a high mortality rate in infants. Our group tested a novel compound, called Dextran-Catechin (DC) in a neuroblastoma xenograft animal model. Recent experiments have provided evidence that the mechanism of action of DC is linked with intracellular copper (Cu) trafficking and distribution. In this work we used [⁶⁴Cu]CuCl₂ to monitor the in vivo Cu distribution in neuroblastoma xenograft mouse models, both with and without treatment.

Materials and Methods: We used human neuroblastoma xenografts using female BALB/c nude mice inoculated with the BE(2)-C cell line. On the day of imaging, 30 min prior to the PET scan, mice were intravenously treated with either saline (100 µL) or DC (300 µg in 100 µL of saline) and anaesthetised using 2% isoflurane. 7-10 MBq of [⁶⁴Cu]CuCl₂ in PBS was injected via the lateral tail vein. PET/CT imaging was performed at 0-2 hr and 5 hr post radiotracer injection. Siemens Inveon IAW 2.0.0.1050 and IRW 4.2.0.8 software were used for image reconstruction and image analysis.

Results: In the pilot study, normal mice demonstrated highest uptake of [⁶⁴Cu]CuCl₂ in the liver (20-30 %ID/g) followed by the kidneys and lungs. We also noticed a considerable uptake in thyroid glands during the first 5 hr (4-7 %ID/g).The tumor tissues showed consistent uptake (2-4 %ID/g) in the saline group, even after 48 hr. ⁶⁴Cu tumor uptake was significantly reduced in DC treated animals.

Conclusion: Previous in vitro studies have shown how DC mediates its beneficial effects via copper metabolism; in this work, we provide in vivo evidence that a single acute dose of DC lowers intracellular Cu levels in neuroblastoma. Future studies will seek to elucidate the molecular basis of action for DC treatment and its potential application in other types of cancer.