Preparation and Evaluation of 177 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 177 Lu and study the preliminary biological behavior of 177 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 177 Lu. The p-NCS-benzyl-DOTA-gemcitabine conjugate was radiolabeled with 177 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: 177 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 177 Lu-gemcitabine for targeted radiotherapy. However, further studies are warranted to assess its potential for radiotherapeutic applications.