Synthesis and optimization of the labeling procedure of 99mTc-Hynic-Interleukin-2 for in vivo imaging of activated T lymphocytes

Abstract

We have previously described the labeling of interleukin-2 (IL2) with 123I and 99mTc-N3S. Both radiopharmaceuticals were successfully applied in humans to image several inflammatory lesions and autoimmune diseases characterized by tissue infiltrating lymphocytes expressing the IL2 receptor (CD25). However, both radiopharmaceuticals had some specific disadvantages, such as cost and time of synthesis. Materials and methods: Here, we describe a new improved method for labeling interleukin-2 with 99mTc using HYNIC-NHS and tricine as coligand. Several optimizations of reagent concentrations and labeling conditions were performed in order to standardize the procedure. After labeling, IL2 was purified by tC2 reverse-phase chromatography and tested in vitro and in vivo, in mice and in a normal volunteer. Results showed that this labeling procedure is cheap, fast, reliable, and reproducible, leading to a product with high specific activity (153 μCi/μg), high stability and capable of binding in vitro to CD25 positive cells. In vivo biodistribution in mice and human volunteer did not show any significant different from 99mTc-N3S-IL2. Conclusion: In conclusion, the optimization of 99mTc-HYNIC-IL2 has a great advantage in terms of cost and time of production and a simple kit formulation can be considered for routine application to study patients affected by autoimmune diseases, graft rejection, or other chronic inflammatory disorders. © 2009 The Author(s).