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, 3 (4), 542-552

Biomathematical Screening of Amyloid Radiotracers With Clinical Usefulness Index


Biomathematical Screening of Amyloid Radiotracers With Clinical Usefulness Index

Ying-Hwey Nai et al. Alzheimers Dement (N Y).


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 [Formula: see text], [Formula: see text], and [Formula: see text].

Results: The relationships of [Formula: see text], [Formula: see text], and [Formula: see text] 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.

Keywords: Alzheimer's disease; Amyloid; Biomathematical model; Clinical usefulness; Positron emission tomography (PET).


Fig. 1
Fig. 1
Overview of the proposed screening methodology for amyloid positron emission tomography radiotracers. (A) Amyloid biomathematical model; (B) amyloid radiotracers' screening methodology. Abbreviations: AD, Alzheimer's disease; AUROC, area under the receiver operating characteristic curve; CUI, clinical usefulness index; HC, healthy control; IF, input function; MCI, mild cognitive impaired; SUVR, standardized uptake value ratio; TACs, time activity curves; 1TCM, 1-tissue-compartment model.
Fig. 2
Fig. 2
Correlations of predicted versus clinically observed (A) K1, (B) k2, and (C) BPND, and (D) SUVR. Abbreviations: AD, Alzheimer's disease; HC, healthy control; BPND, nondisplaceable binding potential; SUVR, standardized uptake value ratio.
Fig. 3
Fig. 3
Simulated SUVR distributions across HC, MCI, and AD conditions for three amyloid PET radiotracers. (A) [11C]PIB; (B) [11C]MeS-IMPY; and (C) [18F]phenylindole-1a. Abbreviations: AD, Alzheimer's disease; HC, healthy control; MCI, mild cognitive impaired; PET, positron emission tomography; SUVR, standardized uptake value ratio.
Fig. 4
Fig. 4
Relationships among Az¯, Es¯, Sr¯, and CUI of 31 amyloid PET radiotracers. Abbreviations: CUI, clinical usefulness index; PET, positron emission tomography.

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