Biomathematical screening of amyloid radiotracers with clinical usefulness index

Introduction To facilitate radiotracers' development, a screening methodology using a biomathematical model and clinical usefulness index (CUI) was proposed to evaluate radiotracers' diagnostic capabilities. Methods A total of 31 amyloid positron emission tomography radiotracers were evaluated. A previously developed biomathematical model was used to simulate 1000 standardized uptake value ratios with population and noise simulations, which were used to determine the integrated receiver operating characteristics curve (Az), effect size (Es), and standardized uptake value ratio (Sr) of conditions-pairs of healthy control–mild cognitive impaired and mild cognitive impaired–Alzheimer's disease. CUI was obtained from the product of averaged Az(Az¯), Es(Es¯), and Sr(Sr¯). Results The relationships of Az¯, Es¯, and Sr¯ with CUI were different, suggesting that they assessed different radiotracer properties. The combination of Az, Es, and Sr complemented each other and resulted in CUI of 0.10 to 5.72, with clinically applied amyloid positron emission tomography radiotracers having CUI greater than 3.0. Discussion The CUI rankings of clinically applied radiotracers were close to their reported clinical results, attesting to the applicability of the screening methodology.