TY - JOUR
T1 - In vivo [18F]-AV-1451 tau-PET imaging in sporadic Creutzfeldt-Jakob disease
AU - Day, Gregory S.
AU - Gordon, Brian A.
AU - Perrin, Richard J.
AU - Cairns, Nigel J.
AU - Beaumont, Helen
AU - Schwetye, Katherine
AU - Ferguson, Cole
AU - Sinha, Namita
AU - Bucelli, Robert
AU - Musiek, Erik S.
AU - Ghoshal, Nupur
AU - Ponisio, Maria R.
AU - Vincent, Benjamin
AU - Mishra, Shruti
AU - Jackson, Kelley
AU - Morris, John C.
AU - Benzinger, Tammie L.S.
AU - Ances, Beau M.
N1 - Funding Information:
G. Day is involved in research supported by an in-kind gift of radiopharmaceuticals from Avid Radiopharmaceuticals, and holds stocks (>$10,000) in ANI Pharmaceuticals (a generic pharmaceutical company). He is funded by an American Brain Foundation Clinical Research Training Fellowship. B. Gordon is participating in a clinical trial examining the utility of the AV-1451 tracer sponsored by Eli Lilly/Avid Radiopharmaceuticals. Neither Dr. Gordon nor his family has direct equity interest in any pharmaceutical or biotechnology company. R. Perrin reports no disclosures. Neither Dr. Perrin nor his family has direct equity interest in any pharmaceutical or biotechnology company. N. Cairns reports no disclosures. Neither Dr. Cairns nor his family has direct equity interest in any pharmaceutical or biotechnology company. H. Beaumont reports no disclosures. Neither Dr. Beaumont nor her family has direct equity interest in any pharmaceutical or biotechnology company. K. Schwetye reports no disclosures. Neither Dr. Schwetye nor her family has direct equity interest in any pharmaceutical or biotechnology company. C. Ferguson reports no disclosures. Neither Dr. Ferguson nor his family has direct equity interest in any pharmaceutical or biotechnology company. N. Sinha reports no disclosures. Neither Dr. Sinha nor her family has direct equity interest in any pharmaceutical or biotechnology company. R. Bucelli has equity in Neuroquestions.com, a neurology board review website, and receives a recurring annual gift from a patient for research in neuralgic amyotrophy. Neither Dr. Bucelli nor his family has direct equity interest in any pharmaceutical or biotechnology company. E. Musiek reports no disclosures. Neither Dr. Musiek nor his family has direct equity interest in any pharmaceutical or biotechnology company. N. Ghoshal has participated or is currently participating in clinical trials of anti-dementia drugs sponsored by the following companies: Bristol-Myers Squibb, Eli Lilly/Avid Radiopharmaceuticals, Janssen Immunotherapy, Novartis,
Funding Information:
Study conduct was made possible by support from the NIH via grants R01NR012907 (B.M.A.), R01NR012657 (B.M.A.), R01NR014449 (B.M.A.), P50AG005681 (J.C.M., T.L.S.B.), P01AG003991 (J.C.M., T.L.S.B.), P01AG026276 (J.C.M., T.L. S.B.), P30NS098577 (T.L.S.B.), and UF01AG032438 (J.C.M., T.L.S.B.); and through generous support via the Paula and Rodger O. Riney Fund (B.M.A.); the Barnes-Jewish Hospital Foundation; and through patient-directed donations made in memoriam (G.S.D.). This study was supported by Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly) who provided the precursor and chemistry support for the production of [18F]-AV-1451, and the doses of [18F]-AV-45. The study authors remain grateful to Mr. Jon J. Christensen for help with data processing. This study discusses the use of [18F]-AV-1451 in research using human participants. [18F]-AV-1451 is an investigational PET radiotracer that is not yet approved by the Food and Drug Administration for any clinical purpose.
Funding Information:
Pfizer, Wyeth, SNIFF (The Study of Nasal Insulin to Fight Forgetfulness) study, and A4 (The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease) trial. She receives research support from Tau Consortium and Association for Frontotemporal Dementia and is funded by NIH grants U01AG045390-01A1 and U54NS092089-01. Neither Dr. Ghoshal nor her family has direct equity interest in any pharmaceutical or biotechnology company. M. Ponisio has nothing to disclose. Neither Dr. Ponisio nor her family has direct equity interest in any pharmaceutical or biotechnology company. B. Vincent has nothing to disclose. Neither Mr. Vincent nor his family has direct equity interest in any pharmaceutical or biotechnology company. S. Mishra has nothing to disclose. Neither Ms. Mishra nor her family has direct equity interest in any pharmaceutical or biotechnology company. K. Jackson has nothing to disclose. Neither Ms. Jackson nor her family has direct equity interest in any pharmaceutical or biotechnology company. J. Morris has participated or is currently participating in clinical trials of anti-dementia drugs including the A4 (The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease) trial and NAVIGATE-AD. Dr. Morris has served as a consultant for Lilly USA. He receives research support from Eli Lilly/Avid Radiopharmaceuticals and is funded by NIH grants P50AG005681, P01AG003991, P01AG026276, and UF01AG032438. Neither Dr. Morris nor his family has direct equity interest in any pharmaceutical or biotechnology company. T. Benzinger has participated or is currently participating in clinical trials of anti-dementia drugs sponsored by Lilly, Roche, DIAN-TU (Dominantly Inherited Alzheimer Network Trials Unit), and A4 (The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease) trial. She receives research support from Eli Lilly/Avid Radiopharmaceuticals and is funded by NIH grants P50AG005681, P01AG003991, P01AG026276, and UF01AG032438. Neither Dr. Benzinger nor her family has direct equity interest in any pharmaceutical or biotechnology company. B. Ances has nothing to disclose. Neither Dr. Ances nor her family has direct equity interest in any pharmaceutical or biotechnology company. He is funded by NIH grants R01NR012907, R01NR012657, and R01NR014449. Go to Neurology.org/N for full disclosures.
Funding Information:
Study conduct was made possible by support from the NIH via grants R01NR012907 (B.M.A.), R01NR012657 (B.M.A.), R01NR014449 (B.M.A.), P50AG005681 (J.C.M., T.L.S.B.), P01AG003991 (J.C.M., T.L.S.B.), P01AG026276 (J.C.M., T.L. S.B.), P30NS098577 (T.L.S.B.), and UF01AG032438 (J.C.M., T.L.S.B.); and through generous support via the Paula and Rodger O. Riney Fund (B.M.A.); the Barnes-Jewish Hospital Foundation; and through patient-directed donations made in memoriam (G.S.D.). This study was supported by Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly) who provided the precursor and chemistry support for the production of [18F]-AV-1451, and the doses of [18F]-AV-45. The study authors remain grateful to Mr. Jon J. Christensen for help with data processing. This study discusses the use of [18F]-AV-1451 in research using human participants. [18F]-AV-1451 is an in-vestigational PET radiotracer that is not yet approved by the Food and Drug Administration for any clinical purpose.
Publisher Copyright:
© 2018 American Academy of Neurology
PY - 2018/3/6
Y1 - 2018/3/6
N2 - Objective To determine whether specific patterns of [18F]-AV-1451 tau-PET retention are observed in patients with autopsy-proven sporadic Creutzfeldt-Jakob disease (CJD). Methods In vivo [18F]-AV-1451 PET neuroimaging was performed in 5 patients with sporadic CJD (median age, 66 years [63-74]), and results were compared to cognitively normal (CN) persons (n = 44; median age, 68 years [63-74]) and to participants with very mild Alzheimer disease (AD) dementia (n = 8; median age, 77 years [63-90]). Autopsy was completed in all patients with CJD, confirming the clinical diagnosis and permitting characterization of AD neuropathologic change (ADNC). Results All patients with CJD presented with rapidly progressive dementia, typical magnetic resonance brain imaging changes, and elevated CSF total tau (median = 6,519; range = 1,528-13,240 pg/ mL). Death occurred within 9 months of symptom onset, with a median 1 month (0.2-3.3) interval from [18F]-AV-1451 PET to autopsy. No unique pattern of [18F]-AV-1451 retention was observed on visual inspection. Summary standardized uptake value ratios in patients with CJD (1.17, 1.08-1.36) were indistinguishable from CN persons (1.14, 0.84-1.54; p = 0.6), and well below those of participants with AD (2.23, 1.60-3.04; p ≤ 0.01). [18F]-AV-1451 retention in patients with CJD and CN persons was similar in brain areas frequently affected in AD and CJD. Neuropathologic analysis confirmed the clinical diagnosis in all patients with CJD. Four patients with CJD also had low-level ADNC (A1B1C0); one patient had intermediate-level ADNC (A2B2C1/2). Conclusion Increased [18F]-AV-1451 retention was not observed in patients with rapidly progressive dementia due to sporadic CJD. The [18F]-AV-1451 PET tracer maintains good specificity for paired helical tau filaments associated with AD dementia.
AB - Objective To determine whether specific patterns of [18F]-AV-1451 tau-PET retention are observed in patients with autopsy-proven sporadic Creutzfeldt-Jakob disease (CJD). Methods In vivo [18F]-AV-1451 PET neuroimaging was performed in 5 patients with sporadic CJD (median age, 66 years [63-74]), and results were compared to cognitively normal (CN) persons (n = 44; median age, 68 years [63-74]) and to participants with very mild Alzheimer disease (AD) dementia (n = 8; median age, 77 years [63-90]). Autopsy was completed in all patients with CJD, confirming the clinical diagnosis and permitting characterization of AD neuropathologic change (ADNC). Results All patients with CJD presented with rapidly progressive dementia, typical magnetic resonance brain imaging changes, and elevated CSF total tau (median = 6,519; range = 1,528-13,240 pg/ mL). Death occurred within 9 months of symptom onset, with a median 1 month (0.2-3.3) interval from [18F]-AV-1451 PET to autopsy. No unique pattern of [18F]-AV-1451 retention was observed on visual inspection. Summary standardized uptake value ratios in patients with CJD (1.17, 1.08-1.36) were indistinguishable from CN persons (1.14, 0.84-1.54; p = 0.6), and well below those of participants with AD (2.23, 1.60-3.04; p ≤ 0.01). [18F]-AV-1451 retention in patients with CJD and CN persons was similar in brain areas frequently affected in AD and CJD. Neuropathologic analysis confirmed the clinical diagnosis in all patients with CJD. Four patients with CJD also had low-level ADNC (A1B1C0); one patient had intermediate-level ADNC (A2B2C1/2). Conclusion Increased [18F]-AV-1451 retention was not observed in patients with rapidly progressive dementia due to sporadic CJD. The [18F]-AV-1451 PET tracer maintains good specificity for paired helical tau filaments associated with AD dementia.
UR - http://www.scopus.com/inward/record.url?scp=85060429119&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000005064
DO - 10.1212/WNL.0000000000005064
M3 - Article
C2 - 29438042
AN - SCOPUS:85060429119
SN - 0028-3878
VL - 90
SP - E896-E906
JO - Neurology
JF - Neurology
IS - 10
ER -