Evaluation of [18F]BMS-754807 as a potential IGF-1R PET tracer for cancer imaging

Objectives Insulin-like growth factor (IGF) is a growth hormone that functions as a regulator of cellular proliferation, apoptosis, energy metabolism and various organ-specific functions. Overexpression of IGF-1R has been found in many cancers, affecting multiple aspects of malignancy such as tumor growth and metastases. We recently reported the radiosynthesis of [18F]BMS-754807, a potent and reversible small molecule dual inhibitor of IGF-1R/IR, which is currently in phase II clinical trials for the treatment of a variety of human cancers. The overall goal of this study is to evaluate [18F]BMS-754807 as a cancer imaging agent in vitro.

Methods [18F]BMS-754807 was obtained by treating corresponding bromo precursor with [18F]TBAF. The proof of concept of IGF-1R imaging with [18F]BMS-754807 was demonstrated by in vitro autoradiography studies using pathologically identified surgically removed breast cancer and pancreatic tumor tissues. Adjacent sections were incubated with known IGF1R inhibitor. The scanned image was analyzed using image analysis software MCID.

Results [18F]BMS-754807 was synthesized in 10-15% yield in excellent purities and specific activity. In vitro autoradiography studies show that [18F]BMS-754807 bind to breast cancer and pancreatic cancer tissues. The radioligand binding was displaced with specific IGF1R inhibitor co-incubated with [18F]BMS-754807.

Conclusions Our studies indicate that [18F]BMS-754807 has the potential for monitoring IGF-1R in breast cancer and pancreatic tumor in vitro. Further studies are required to establish the in vivo potential of [18F]BMS-754807. The details of in vitro evaluation of the radioligand will be presented.