In vitro evaluation of [18F]BMS-754807, a selective IGF1R radiotracer in human brain

Objectives We recently developed [18F]BMS-754807 and successfully evaluated the tracer in vitro in a variety of human cancers and tumors. IGF1R also plays critical role in brain development, normal brain functions and its alteration is reported in the pathophysiology of a variety of central nervous system disorders such as Alzheimer’s disease, Traumatic Brain Injury, Amyotrophic Lateral Sclerosis, Fredreich Ataxia and aging. In this study we investigated the binding of [18F]BMS-754807 in normal brain tissues and examined its binding in Alzheimer’s Disease tissues in comparison to control brain tissues using autoradiography technique.

Methods The radiosynthesis of [18F]BMS-754807 was achieved by reacting the bromo-precursor with [18F]TBAF. In vitro autoradiography studies of [18F]BMS-754807 were initially performed in normal postmortem human tissues to establish the optimal conditions followed by testing in pathologically identified brain sections of Alzheimer’s Disease in comparison to controls. The specific binding of [18F]BMS-754807 binding was determined by co-incubating the adjacent sections with a known IGF1R inhibitor. The scanned image was analyzed using image analysis software MCID.

Results Radioligand [18F]BMS-754807 was synthesized in 10-15% yield (EOS). Very high specific binding (>80%) was found in the autoradiograms. An alteration of radioligand binding was observed in Alzheimer’s disease tissues such as frontal cortex, striatum and hippocampus in comparison to control brain sections.

Conclusions Our studies demonstrated the alteration of IGF1R in Alzheimer’s disease in comparison to control. IGF1R can be a good biomarker for the diagnosis of Alzheimer’s disease.