Preclinical properties and human in vivo assessment of 123I-ABC577 as a novel SPECT agent for imaging amyloid-β

Non-invasive imaging of amyloid-beta in the brain, a hallmark of Alzheimer's disease, may support earlier and more accurate diagnosis of the disease. In this study, we assessed the novel single photon emission computed tomography tracer I-123-ABC577 as a potential imaging biomarker for amyloid-beta in the brain. The radio-iodinated imidazopyridine derivative I-123-ABC577 was designed as a candidate for a novel amyloid-beta imaging agent. The binding affinity of I-123-ABC577 for amyloid-beta was evaluated by saturation binding assay and in vitro autoradiography using post-mortem Alzheimer's disease brain tissue. Biodistribution experiments using normal rats were performed to evaluate the biokinetics of I-123-ABC577. Furthermore, to validate I-123-ABC577 as a biomarker for Alzheimer's disease, we performed a clinical study to compare the brain uptake of I-123-ABC577 in three patients with Alzheimer's disease and three healthy control subjects. I-123-ABC577 binding was quantified by use of the standardized uptake value ratio, which was calculated for the cortex using the cerebellum as a reference region. Standardized uptake value ratio images were visually scored as positive or negative. As a result, I-123-ABC577 showed high binding affinity for amyloid-beta and desirable pharmacokinetics in the preclinical studies. In the clinical study, I-123-ABC577 was an effective marker for discriminating patients with Alzheimer's disease from healthy control subjects based on visual images or the ratio of cortical-to-cerebellar binding. In patients with Alzheimer's disease, I-123-ABC577 demonstrated clear retention in cortical regions known to accumulate amyloid, such as the frontal cortex, temporal cortex, and posterior cingulate. In contrast, less, more diffuse, and non-specific uptake without localization to these key regions was observed in healthy controls. At 150 min after injection, the cortical standardized uptake value ratio increased by similar to 60% in patients with Alzheimer's disease relative to healthy control subjects. Both healthy control subjects and patients with Alzheimer's disease showed minimal I-123-ABC577 retention in the white matter. These observations indicate that I-123-ABC577 may be a useful single photon emission computed tomography imaging maker to identify amyloid-beta in the human brain. The availability of an amyloid-beta tracer for single photon emission computed tomography might increase the accessibility of diagnostic imaging for Alzheimer's disease.