TY - JOUR
T1 - Dynamic Amyloid PET
T2 - Relationships to 18F-Flortaucipir Tau PET Measures
AU - Raman, Fabio
AU - Fang, Yu Hua Dean
AU - Grandhi, Sameera
AU - Murchison, Charles F.
AU - Kennedy, Richard E.
AU - Morris, John C.
AU - Massoumzadeh, Parinaz
AU - Benzinger, Tammie
AU - Roberson, Erik D.
AU - McConathy, Jonathan
N1 - Funding Information:
Data used in the preparation of this article were obtained from the Charles F. and Joanne Knight Alzheimer Disease Research Center at the Washington University in St. Louis and are available on request (https://knightadrc.wustl.edu/). 18F-flortaucipir was produced under a material transfer agreement between Washington University and Avid Radiopharmaceuticals.
Funding Information:
This work was supported by National Institutes of Health grants P20AG068024, RF1AG059009, and T32GM008361; the Medical Science Training Program, the Alzheimer Drug Discovery Foundation, and the Department of Radiology at the University of Alabama at Birmingham. Tammie Benzinger is funded by NIH grants P50AG005681, P01AG003991, P01AG026276, UF01AG032438, R01AG05326, RF1AG053550, R01AG054567, and R01AG052550. John Morris is funded by NIH grants P50AG005681, P01AG003991, P01AG026276, and UF01AG032438. The recruitment of participants and their clinical characterization and neuroim-aging were supported by NIH grants P50AG05681, P01AG03991, and P01AG026276. Avid Radiopharmaceuticals, which is a wholly owned subsidiary of Eli Lilly (18F-florbetapir and 18F-flortaucipir imaging), provided the 18F-florbetapir doses and partial support for 18F-florbetapir scanning through an investigator-initiated research grant awarded to Washington University (John Morris and Tammie Benzinger); provided technology transfer; and provided precursor for 18F-florbetapir. Jonathan McConathy has declared a relationship with Eli Lilly and Avid, to which he provides consulting and from which he receives research support. No other potential conflict of interest relevant to this article was reported.
Publisher Copyright:
COPYRIGHT © 2022 by the Society of Nuclear Medicine and Molecular Imaging.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - Measuring amyloid and predicting tau status using a single amyloid PET study would be valuable for assessing brain AD pathophysiology. We hypothesized that early-frame amyloid PET (efAP) correlates with the presence of tau pathology because the initial regional brain concentrations of radioactivity are determined primarily by blood flow, which is expected to be decreased in the setting of tau pathology. Methods: The study included 120 participants (63 amyloid-positive and 57 amyloid-negative) with dynamic 18F-florbetapir PET and static 18F-flortaucipir PET scans obtained within 6 mo of each other. These subjects were predominantly cognitively intact in both the amyloid-positive (63%) and the amyloid-negative (93%) groups. Parameters for efAP quantification were optimized for stratification of tau PET positivity, assessed by either a tauopathy score or Braak regions. The ability of efAP to stratify tau positivity was measured using receiver-operating-characteristic analysis of area under the curve (AUC). Pearson r and Spearman r were used for parametric and nonparametric comparisons between efAP and tau PET, respectively. Standardized net benefit was used to evaluate improvement in using efAP as an additional copredictor over hippocampal volume in predicting tau PET positivity. Results: Measuring efAP within the hippocampus and summing the first 3 min of brain activity after injection showed the strongest discriminative ability to stratify for tau positivity (AUC, 0.67-0.89 across tau PET Braak regions) in amyloid-positive individuals. Hippocampal efAP correlated significantly with a global tau PET tauopathy score in amyloid-positive participants (r 5 20.57, P, 0.0001). Compared with hippocampal volume, hippocampal efAP showed a stronger association with tau PET Braak stage (r 5 20.58 vs. 20.37) and superior stratification of tau PET tauopathy score (AUC, 0.86 vs. 0.66; P 5 0.002). Conclusion: Hippocampal efAP can provide additional information to conventional amyloid PET, including estimation of the likelihood of tau positivity in amyloid-positive individuals.
AB - Measuring amyloid and predicting tau status using a single amyloid PET study would be valuable for assessing brain AD pathophysiology. We hypothesized that early-frame amyloid PET (efAP) correlates with the presence of tau pathology because the initial regional brain concentrations of radioactivity are determined primarily by blood flow, which is expected to be decreased in the setting of tau pathology. Methods: The study included 120 participants (63 amyloid-positive and 57 amyloid-negative) with dynamic 18F-florbetapir PET and static 18F-flortaucipir PET scans obtained within 6 mo of each other. These subjects were predominantly cognitively intact in both the amyloid-positive (63%) and the amyloid-negative (93%) groups. Parameters for efAP quantification were optimized for stratification of tau PET positivity, assessed by either a tauopathy score or Braak regions. The ability of efAP to stratify tau positivity was measured using receiver-operating-characteristic analysis of area under the curve (AUC). Pearson r and Spearman r were used for parametric and nonparametric comparisons between efAP and tau PET, respectively. Standardized net benefit was used to evaluate improvement in using efAP as an additional copredictor over hippocampal volume in predicting tau PET positivity. Results: Measuring efAP within the hippocampus and summing the first 3 min of brain activity after injection showed the strongest discriminative ability to stratify for tau positivity (AUC, 0.67-0.89 across tau PET Braak regions) in amyloid-positive individuals. Hippocampal efAP correlated significantly with a global tau PET tauopathy score in amyloid-positive participants (r 5 20.57, P, 0.0001). Compared with hippocampal volume, hippocampal efAP showed a stronger association with tau PET Braak stage (r 5 20.58 vs. 20.37) and superior stratification of tau PET tauopathy score (AUC, 0.86 vs. 0.66; P 5 0.002). Conclusion: Hippocampal efAP can provide additional information to conventional amyloid PET, including estimation of the likelihood of tau positivity in amyloid-positive individuals.
UR - http://www.scopus.com/inward/record.url?scp=85112370140&partnerID=8YFLogxK
U2 - 10.2967/JNUMED.120.254490
DO - 10.2967/JNUMED.120.254490
M3 - Article
C2 - 34049986
AN - SCOPUS:85112370140
VL - 63
SP - 287
EP - 293
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
SN - 0161-5505
IS - 2
ER -