Evidence suggests that the abnormal levels of Amyloid beta (A) species in brains appear as early as 30 years before symptom starts in Alzheimer’s disease (AD) patients. However, the early generation PET probes can only detect the abnormal A deposits close to the onset of clinical AD syndrome. In this report, we demonstrated that half-curcuminoid could be a better scaffold for PET tracer development. Through blocking a highly reactive site of half-curcuminoids, F-CRANAD-101 was designed and showed significant responses to both soluble and insoluble Aβs in fluorescent spectral tests. PET imaging results indicated that both 14-month and 5-month APP/PS1 AD mice had higher signals in brain than the age-matched wild type mice. We believe that [18F]-CRANAD-101 could be a potential PET imaging probe for Amyloid betas in Alzheimer’s disease.