Synthesis of a ¹¹C-Isotopologue of the B-Raf-Selective Inhibitor Encorafenib Using In-Loop [¹¹C]CO₂ Fixation

Area of Science:

• Biochemistry
• Radiochemistry
• Oncology

Background:

• B-Raf is a key regulator of cell growth, and its elevated expression in melanoma makes it a target for imaging.
• Encorafenib, a B-Raf inhibitor, is used clinically for melanoma treatment.

Purpose of the Study:

• To develop a radiosynthesis method for a carbon-11 labeled isotopologue of encorafenib ([¹¹C]encorafenib).
• To evaluate the feasibility of using [¹¹C]encorafenib for noninvasive imaging of B-Raf in melanoma.

Main Methods:

• Radiosynthesis of [¹¹C]encorafenib was achieved via an in-loop [¹¹C]CO₂ fixation reaction.
• Reaction conditions were optimized to improve radiochemical yield and reduce side products.
• The process was automated using a commercial radiosynthesizer.

Main Results:

• Optimized radiosynthesis yielded [¹¹C]encorafenib with 14.5 ± 2.4% radiochemical yield.
• Automated production yielded 6845 ± 888 MBq of [¹¹C]encorafenib with high molar activity (177 ± 5 GBq μmol⁻¹) and radiochemical purity (99%).
• In vitro studies showed saturable binding of the radiotracer to A375 melanoma cells.

Conclusions:

• A robust and automated radiosynthesis of [¹¹C]encorafenib was successfully developed.
• [¹¹C]encorafenib is a promising radiotracer for noninvasive imaging of B-Raf in melanoma.
• Further studies are warranted to evaluate its diagnostic potential in vivo.