Preparation and Evaluation of Lu-Labeled Gemcitabine: An Effort Toward Developing Radiolabeled Chemotherapeutics for Targeted Therapy Applications.

OBJECTIVE

Gemcitabine, a nucleoside analogue, is used as a chemotherapeutic drug for the treatment of a wide variety of cancers. Therefore, radiolabeled gemcitabine may have potential as a radiotherapeutic agent for the treatment of various types of cancers. In the present work, an attempt has been made to radiolabel gemcitabine with Lu and study the preliminary biological behavior of Lu-labeled gemcitabine in tumor-bearing animal model.

EXPERIMENTAL

Gemcitabine was coupled with p-NCS-benzyl-DOTA, a bifunctional chelating agent, to facilitate radiolabeling with Lu. The p-NCS-benzyl-DOTA-gemcitabine conjugate was radiolabeled with Lu, produced in-house and characterized by high-performance liquid chromatography. Tumor targeting potential of the radiolabeled agent was determined by biodistribution studies in Swiss mice bearing fibrosarcoma tumors.

RESULTS

Lu-gemcitabine was prepared with a radiochemical purity of 95.7% ± 0.3% under the optimized reaction conditions. The radiolabeled agent showed adequate in vitro stability in normal saline as well as in human blood serum. Preliminary biological studies revealed rapid and significant accumulation of the radiotracer in the tumorous lesions along with fast clearance of activity from blood and other vital organs/tissue. Although tumor uptake gradually reduced with time, tumor to blood and tumor to muscle ratios were improved due to the comparatively faster clearance of activity from the nontarget organs/tissue.

CONCLUSION

The present study demonstrates the preliminary potential of Lu-gemcitabine for targeted radiotherapy. However, further studies are warranted to assess its potential for radiotherapeutic applications.