F 18 T807 Tau PET Imaging in Familial Amyotrophic Lateral Sclerosis (IND 123119 Protocol B)
Conditions: Amyotrophic Lateral Sclerosis (ALS)
Sponsor: Tammie L. S. Benzinger, MD, PhD

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Protocol Title: 
F 18 T807 tau PET imaging in familial amyotrophic 
lateral sclerosis (IND 123119, Protocol B) 
 
Principal Investigator: 
Tammie L.S. Benzinger, M.D., Ph.D. 
Assistant Professor of Radiology and Neurological Surgery 
Mallinckrodt Institute of Radiology 
Washington University School of Medicine  
510 S. Kingshighway Blvd., Campus Box 8131 
St. Louis, MO  63110 
Office: 314-362-1558 
Fax:  314-362-6110 
benzingert@wustl.edu 
 
Study Product: 
18F-AV-1451 (also known as [F-18]T807 or LY3191748) 
Protocol: 
Protocol B 
Version: 
4 
Version Date: 
April 30, 2018  
IND Number: 
123119 
 
 
 
 
 
 
 

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Revisions 
 
Revision 3, 04/30/2018 
1. Protocol version date and number were updated. 
2. Additional study team list was deleted on page 6. 
3. Research lab manager and Imaging Coordinator’s information was deleted 
4. The following was added to “Inclusion Criteria”  #4:  Females of childbearing potential without 
documented history of menopause or hysterectomy who do participate must not be pregnant  or 
breastfeeding at screening (negative urine β-HCG within 24 hours prior to injection of 
radioactivity), and must agree to avoid becoming pregnant. 
5. The following was added to “Exclusion Criteria” #8 Females of childbearing potential who do 
not agree to use reliable contraception or refrain from sexual activity for 24 hours following 
administration of flortaucipir injection will be excluded. 
6. The risk language associated with 18F-AV-1451 was changed. In the “less likely” section was 
changed to include nausea, lightheadedness/dizziness. In the “rare” section we added that 
“Some participants may experience atrial fibrillation and transient ischemic attack. 
 
Revision 2, 10/29/2015 
1. Removed the following people from the study team: Swapnil Bagade, Eric Byrum, Delphine 
Chen, Keith Fischer, Linga Reddy, Henry Royal, Kiran Sargar, Akash Sharma, Houman 
Sotoudeh, Marcus Raichle, Jerold Wallis, Spencer McFarlane. 
2. Update scanner-related risks regarding skin tattoos with MRI. 
 
Revision 1, 04/07/2015 
1. Re-listed Spencer McFarlane from Study Coordinator to Additional Study Team Member.  
Kelley Jackson now listed as Study Coordinator. 
2. Listed the following individuals on the protocol under Additional Study Team Member: Lisa 
Cash, Tony Durbin, Karl Friedrichsen, Russell Hornbeck, Christopher Owen, Betsy Thomas, 
Elizabeth Westerhaus 
3. Added the following individuals as new Additional Study Team Members: Dr. Swapnil Bagade, 
Linda Becker, Dr. George Benzinger, Tyler Blazey, Dr. Eric Byrum, Dr. Delphine L. Chen, Dr. 
Farrokh Dehdashti, Dr. Keith C. Fischer, Dr. Nupur Ghoshal, Dr. Brian Gordon, Dr. Manu 
Goyal, Emily Gremminger, Nancy Hantler, Michael Harrod, Dr. Pamela LaMontagne, Dr. 
Parinaz Massoumzadeh, Dr. John C. Morris, Dr. Maria Ponisio, Dr. Jing Qi, Dr. Marcus E. 
Raichle, Dr. Henry D. Royal, Dr. Kiran Sargar, Dr. Joshua S. Shimony, Dr. Barbara Joy Snider, 
Dr. Houman Sotoudeh, Dr. Yi Su, Dr. Andrei Vlassenko, Dr. Jerold W. Wallis, Dr. Pamela 
Woodard. 
4. Under Inclusion Criteria, specified that women of childbearing potential will have a negative 
urine pregnancy test 24 hours prior to  F 18 T807 drug administration. 
5. We are now allowing for a non-physician designee to conduct participant assessment prior to 
T807 injection and prior to discharge from F 18 T807 imaging visit. 
6. For Exclusion Criterion# 3, we have referenced a study-specific list of restricted medications. 
7. The F 18 T807 PET acquisition protocol for the long scan has been revised such that we have 
the option of scanning for 105 continuous minutes, with a break of up to 15 minutes to be 
offered to the participant. 
8. Clarified that a second CT attenuation scan may be conducted for the T807 long scan.  In the 
event the participant needs to get off the scanner bed for a break, a second CT attenuation can 
be conducted. 
9. Updated radiation risk statement, as related to the second CT attenuation scan (see #5 above). 

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10. Added statement that for those participating in the optional 18F-FDG PET scan, participants 
must fast for 4 hours prior to 18F-FDG injection. It is also clarified that prior to 18F-FDG 
injection, a blood sample will be taken for glucose measurement.   
11. We added option to do short FDG scan acquisition. 
12. Vital signs will now be collected prior to F 18 T807 administration. 
13. We will now be asking participants about history of traumatic brain injury using the Ohio State 
University Traumatic Brain Injury Identification (OSU TBI-ID) Method.   
14. Clarified that women of childbearing potential who elect to undergo PET imaging with 18F-
FDG must have a negative urine pregnancy test no later than 4 days prior to the 18F-FDG  
imaging session. 
15. Description of MRI risks were updated to match wording in the other protocols under IND 
123119. 
16. Under 6.f. Scanner Procedures, Section (iv) was corrected to note that MR imaging may be 
conducted at the same time as the 18F-FDG PET scan if conducted on the PET/MR scanner. 
17. Revised neuropsychometric battery. 
18. Updated Serious Adverse Event Reporting section to include reporting guidelines to Avid 
Radiopharmaceuticals/Eli Lilly. 
19. Updated protocol version to Version 2 and protocol date to 04/07/2015. 
 
 

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Sub-Investigators and Team Members 
 
Sub-Investigators: 
Matthew B. Harms, M.D. 
Washington University School of Medicine 
Department of Neurology 
660 South Euclid Ave., Campus Box 8111 
St. Louis, MO  63110 
Tel: 314-362-2155 
 
 
 
Fax: 314-362-3752 
 
 
 
harmsm@neuro.wustl.edu 
 
 
 
 
Timothy M. Miller, MD, PhD 
Washington University School of Medicine 
Department of Neurology 
660 South Euclid Ave., Campus Box 8111 
St. Louis, MO  63110 
 
 
 
Tel: 314-362-8169 
Fax:314-3279 
 
 
 
millert@neuro.wustl.edu 
 
 
 
Beau M. Ances, M.D., Ph.D. 
Department of Neurology 
Washington University School of Medicine  
660 S. Euclid, Campus Box 8111 
St. Louis, Missouri, 63110 
Tel: 314-747-8423 
Fax: 314-362- 6110 
ancesb@neuro.wustl.edu  
 
 
    
 
 
 

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Protocol Table of Contents 
 
1.     Overview 
 
 
 
 
2.     Objectives 
3.     Background Information 
4.     Statement of Qualifications 
5.     Inclusion/Exclusion Criteria 
6.     Methods 
7.     Informed Consent 
8.     Procedures for Maintaining Confidentiality 
 
9.     Assessment of Risks and Benefits 
10.   Benefits 
11.   Regulatory and Reporting Requirements 
12.   Case Report Forms 
13.   Record Archives 
14.   References 
 
 
 
 
 
 
 
 
 

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1. 
Overview 
Tau aggregation and deposition in the form of neurofibrillary tangles is a major pathological 
hallmark of Alzheimer’s disease (AD) pathology and is thought to represent a final common 
pathway for multiple neurodegenerative disorders, ranging from frontotemporal dementia, to 
Parkinsonism, to certain genetic forms of amyotrophic lateral sclerosis (ALS) [1-3].  In AD, 
where tau pathology has been best studied, postmortem studies demonstrate a progressive 
spreading, or staging, of tau pathology, beginning in the transentorhinal cortex, progressing 
through the temporal lobe and into the frontal and parietal lobes, and finally becoming diffuse 
[2, 4, 5].  It has been recently appreciated that tau deposition can be a significant pathological 
feature in some forms of familial ALS, and is especially prominent in cases caused by mutations 
in the C9ORF72 gene.  We have hypothesized that tau deposition may predict greater cognitive 
involvement and faster rates of disease progression.  However, for all diseases with tau 
deposition, including AD and ALS, we have lacked the ability to stage the distribution and 
amount of tau pathology in vivo.  In the last year however, new PET imaging tracers have been 
developed which are likely to revolutionize the field [6-8].   
The optimum scanning and data analysis approaches, however, are still unclear. This project 
will collect quantitative pilot data that will allow the characterization of uptake and binding of 
18F-AV-1451 (also known as F 18 T807, also known as 7-(6-fluoropyridin-3-yl)-5H-pyrido[4,3-
b]indole), a novel tau imaging compound, in individuals with and without brain tau fibrils. The 
primary goal of this study is to develop this highly promising tau imaging technique as an 
antecedent biomarker of neuronal cell loss, regardless of whether that loss leads to cognitive 
decline (as in AD) or to weakness and fronto-temporal dementia (as in ALS).  That is, we 
propose to obtain preliminary data that will support the possibility of detecting cognitive decline 
or neuronal loss in its earliest stages, before the occurrence of dementia or the onset of 
weakness.  Preliminary data generated from this study will be used for submission of National 
Institutes of Health (NIH) grants investigating neurodegenerative disorders that include, but are 
not exclusive to, AD, ALS, frontotemporal dementia (FTD), Parkinson disease, and HIV-
Associated Neurocognitive Disorders (HAND). 
Under this study protocol, collaborating neuromuscular physicians will refer participants for 
MR and PET imaging to evaluate tau distribution in the brain of subjects with ALS, or ALS 
with frontotemporal dementia caused by different genetic mutations, or any mutation carrier 
(with or without symptoms), or normal controls. 

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We hypothesize that in vivo tau imaging will ultimately: 
• Demonstrate the presence of tau fibrils in the brain of subjects with ALS or ALS with 
fronto-temporal dementia, especially in those with mutations in C9ORF72,  and may 
discriminate between ALS causes by C9ORF72 and mutations in other genes.  
• Demonstrate that cortical F 18 T807 uptake correlates with markers of ALS disease 
severity, degrees of cognitive impairment, and rates of decline. 
• Demonstrate correlations between F 18 T807 uptake with CSF markers of tau, including 
tau and p-tau. 
• Co-localize with specific cognitive deficits (i.e. patients with tau deposition in the left 
lateral temporal lobe will have primarily language deficits). 
2. 
Objectives 
To begin to explore these hypotheses, we will pursue the following specific aims (SA). 
SA1:  Perform human in vivo tau imaging using F 18 T807 in 20 participants age 18 and 
older.  Participants will have biomarker imaging and CSF assessments, and clinical and 
psychometric assessments. 
 
SA2: Develop quantitative analysis methods for F 18 T807 PET scans. 
 
Exploratory SA3:  Correlate regional quantitative T807 binding potentials (BPs) with 
(a) presence and progression of cognitive impairment and weakness, as documented by 
clinical psychometric and strength testing, with (b) brain atrophy by volumetric MRI, (c) 
CSF and amyloid imaging markers of AD pathology, (d) performance on psychometric 
tests, (e) clinical diagnosis, and, if the participant expires, (f) autopsy findings.   
 
3. 
Background Information 
C9ORF72-associated disease: 
A hexanucleotide repeat expansion in an intron of the C9ORF72 gene was recently identified as 
the most common cause of two fatal diseases characterized by progressive neuronal 
degeneration- amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD)[9].  
Early pathological studies in C9ORF72 repeat expansion carriers highlighted the prevalence of 
cytoplasmic TDP-43 and p62 aggregate pathology[10, 11].  As the toxic-RNA mechanisms 
have been uncovered, more pathognomonic findings have also been found, including nuclear 
RNA foci and cytoplasmic aggregates of RANT-generated dipeptides[12].  In our early clinic-

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pathologocial studies of C9ORF72 carriers, we uncovered a subset of patients whose neurons 
demonstrated significant accumulation of intracellular tau fibrils[13].  Subsequent publications 
have confirmed that in some cases, the burden of tau neurofibrillary tangles (NFTs) is sufficient 
to meet criteria for Alzheimer’s disease (AD).  The burden of tau pathology in C9ORF72 
disease has been found to be equivalent to that observed in other forms of frontotemporal 
dementia and high levels of tau and phosphorylated tau have been observed in CSF from 
patients with C9ORF72 expansions[14, 15].  These data highlight a potential role for tau 
pathology in C9ORF72-associated neurodegeneration.  As in other neurodegenerative diseases 
with tau pathology, tau aggregation could exacerbate C9ORF72-specific mechanisms of 
degeneration[16].  We hypothesize that the degree and distribution of cortical tau pathology in 
C9ORF72 expansion carriers will correlate with the likelihood of cognitive dysfunction and 
with faster rates of disease progression.  We propose leveraging a novel tau imaging tracer 
available here at Washington University to obtain pilot data addressing this novel hypothesis 
and to explore the cortical tau burden as a potential biomarker in C9ORF72 diseases. 
 
 
 
 
 
 
Figure 1:  Chemical structure of T807 
18F-AV-1451 (also known as F 18 T807, also known as 7-(6-fluoropyridin-3-yl)-5H-pyrido[4,3-
b]indole) is a novel in vivo human tau PET imaging agent [6, 17].  It was initially developed 
through screening of human AD brain sections, combining autoradiography and 
immunostaining, and has undergoing initial human studies including toxicology and radiation 
dosimetry.  Preliminary results suggest it can stage tau pathology in a manner similar to Braak 
and Braak staging.   

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4. 
Statement of Qualifications 
The FDA 1572 Form is provided in the IND submission (see Appendix II) along with 
curriculum vitae (see Appendix III) for the study’s Principal Investigator, Tammie L.S. 
Benzinger, M.D., Ph.D., Washington University School of Medicine, St. Louis, Missouri. 
5. 
Inclusion/Exclusion Criteria 
All participants will be evaluated for the following: 
Inclusion Criteria 
1.   Male or female participants, at least 18 years of age.     
2.   Clinically diagnosed with amyotrophic lateral sclerosis (ALS), fronto-
temporal dementia (FTD), or both; or a carrier of a mutation known to cause 
ALS or FTD (with or without symptoms); or a normal control. 
3.   Participant is able and willing to undergo testing (psychometric testing, MRI 
or CT, PET, radioactive tracer injection; for those unable to undergo an MRI, CT 
will be used to generate regions-of-interest). 
4.   Females of childbearing potential without documented history of menopause 
or hysterectomy who do participate must not be pregnant  or breastfeeding at 
screening (negative urine β-HCG within 24 hours prior to injection of 
radioactivity), and must agree to avoid becoming pregnant. 
 
 
Exclusion Criteria 
1.   Has any condition that, in the Investigator’s opinion, could increase risk to 
the participant, limit the participant’s ability to tolerate the experimental 
procedures, or interfere with the collection/analysis of the data (for example, 
participants with significant respiratory involvement may not be able to lie flat 
during the scanning procedures). 
2.   Is deemed likely unable to perform the imaging procedures for any reason. 
3.   Has a high risk for Torsades de Pointes or is taking medications known to 
prolong or may prolong QT interval (refer to study’s list of restricted 
medications). 
4.   Has hypersensitivity to F 18 T807 or any of its excipients. 

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5.   Contraindications to PET, PET-CT or MR (e.g. electronic medical devices, 
inability to lie still for long periods) that make it unsafe for the individual to 
participate. 
6.   Severe claustrophobia. 
7.   Currently pregnant or breast-feeding. 
8. Females of childbearing potential who do not agree to use reliable 
contraception or refrain from sexual activity for 24 hours following the 
administration of flortaucipir injection will be excluded. 
6. 
Methods 
a. Study Design 
A single-center, open-label baseline controlled imaging study designed to assess whether 
brain tau fibril uptake of F 18 T807 as measured by PET correlates with cognitive and clinical 
status of individuals with and without brain tau fibrils. 
b. Participant Population 
Twenty (20) participants over a period of approximately 5 years will be enrolled.  
Participants will undergo an F 18 T807 scan at the Center for Clinical Imaging Research 
(CCIR) at Washington University using an adaption of the protocol developed by Kolb and 
colleagues [6].  An MRI will be conducted.  (For those unable to undergo an MRI, CT will 
be used to generate regions-of-interest.)  Participants will be asked about their medical 
history, family history, surgical history, and current medications.  We will evaluate history 
of traumatic brain injury using the Ohio State University Traumatic Brain Injury 
Identification (OSU TBI-ID) Method.  This will take approximately 10 minutes.  
Additionally, participants will be invited to undergo the following assessments:  
i) PET imaging with fludeoxyglucose (18F-FDG), for measurement of the cerebral 
metabolic rate of glucose consumption. 
ii) A physical examination (if one has not been conducted under IRB ID# 201312111). 
c. Recruitment 
Participants will be referred to an imaging research coordinator on the Principal 
Investigator’s study team.  The research coordinator will discuss the study with the 
participant over the phone and conduct a pre-screening assessment.  The research 
coordinator will have access to the health history data collected by the referring physician at 
the participant’s most recent assessment.  The research coordinator will review the 

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participant’s general health information with the participant to assess any contraindications 
to PET or MR imaging.  If the participant appears to be eligible, they will be given a consent 
form to read, review, and discuss with others who may be able to help them make a decision 
about participating in the study.  Study staff will provide adequate time for the participant to 
ask questions to ensure that any concerns are addressed prior to study enrollment.   
d. Imaging Study Procedures 
i) F 18 T807 Imaging 
Participants will undergo a PET scan using the tau-imaging tracer, F 18 T807.  
Participants will come to the imaging center and will have a catheter placed for 
intravenous (i.v.) administration of F 18 T807.  Participants will receive a single 6.5-10 
mCi intravenous bolus of F 18 T807 infused over 20 seconds.  Participants may also 
undergo up to two low dose CT scans for attenuation correction.   
 
There are two acceptable procedures for obtaining the F 18 T807 PET scans:   
1) In the preferred approach, participants will receive a single IV bolus injection of 
approximately (240-370 MBq) 6.5-10 mCi of F 18 T807, followed by a saline 
flush.  Scanning will start at the same time as the injection and continue for a 
total of 105 minutes.  If needed, the participant may take up to a 15-minute break 
after the first 60 minutes of scanning, and scanning should resume immediately 
after the break.  For the 60 minutes, PET data will be acquired in 3-dimensional 
list mode and will be binned into 38 dynamic frames (10 frames × 6 s, 6 frames ×  
20 s, 4 frames × 30 s, 5 frames × 60 s, 5 frames × 120 s, 8 frames × 300 s).  After 
the break, the PET data will be acquired in 5-minute frames and will be summed 
into one static frame.  This imaging visit will take approximately two hours. 
2) For those who cannot tolerate the full exam, participants will receive a single IV 
bolus injection of approximately (240-370 MBq) 6.5-10 mCi of F 18 T807, 
followed by a saline flush.  Participants will rest quietly in an uptake room 
following the injection.  At approximately 75 minutes following injection, a 
continuous 30 minute brain scan (6 acquisitions of 5 minute duration) will be 
performed.  This imaging visit will take approximately two hours. 
 
The following safety assessments will be performed at the time of the F 18 T807 PET 
imaging session: 

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1) A physician, or a licensed/credentialed medical professional (i.e., a PET 
technologist, imaging center nurse, or a regional equivalent) designated by the 
Principal Investigator,  must assess or evaluate the participant prior to 
administration of F 18 T807 injection to determine if they are still suitable to 
undergo the scan. If a designee performs this activity, a physician must be 
available to provide medical attention; 
2) For women of childbearing potential, a negative urine pregnancy test must be 
obtained up to 24 hours prior to F 18 T807 dose administration; 
3) Vital signs will be taken prior to F 18 T807 dose administration; 
4) The injection site will be observed for evidence of inflammation or damage to 
the surrounding tissue where the dose was injected;  
5) The participant will be requested to void after completion of the PET scan; 
6) Adverse events (AEs) will be continuously monitored during the F 18 T807 
imaging session; participants who experience an AE will not be discharged from 
the imaging center until the event has resolved or stabilized; and 
7) A physician, or a licensed/credentialed medical professional (i.e., a PET 
technologist, imaging center nurse, or a regional equivalent) designated by the 
Principal Investigator,  will evaluate the subject prior to discharge from the 
imaging center to evaluate the subject’s readiness for discharge.  If a designee 
performs this activity, a physician must be available to provide medical attention. 
 
A follow-up phone call to the participant will be conducted within 2 or 3 business days 
of the F 18 T807 imaging visit, but not before 48 hours post-injection, to confirm 
participant well-being and to collect information about any new adverse events.   
ii) MR Imaging 
Participants will be asked to undergo an MRI scan.  (For those unable to undergo an 
MRI, CT will be used to generate regions-of-interest.)  MR imaging will be formed 
using the established Washington University protocols for dementia imaging.  These 
include T1-weighted magnetization-prepared rapid gradient echo (MPRAGE) sequence 
(1 mm isotropic voxels).  This scan will take approximately one hour. 
iii) 18F-FDG Imaging (Optional) 
Participants will be invited to undergo an optional 18F-FDG PET scan. 18F-FDG uptake 
and trapping may be used to image the cerebral metabolic rate of glucose consumption 

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(CMRGlc).  Participants will be asked to fast for 4 hours prior to injection of 18F-FDG.  
Women of childbearing potential must have a urine pregnancy test no later than 4 days 
prior to 18F-FDG dose administration. Prior to the 18F-FDG PET scan, an antecubital 
intravenous catheter will be placed in the arm for tracer injection and blood sampling for 
glucose levels.  Blood sampling will be done once prior to FDG tracer injection.  
Measurements of CMRGlc will be performed after slow intravenous injection of 5 mCi 
of 18F-FDG. Dynamic acquisition of PET emission data will continue for 60 minutes 
according to the following scheme: 25 x 5 sec frames, 9 x 20 sec frames, 10 x 60 sec 
frames, 9 x 300 sec frames. All data will be corrected for head motion that occurs during 
the 18F-FDG scan.  This scan will take approximately one hour.  For those unable to 
tolerate a full 60-minute dynamic scan, a 30 minute scan may be conducted 30 minutes 
after 18F-FDG administration. 
 
e. Participant Preparation 
Participants will be asked to arrive at the Center for Clinical Imaging Research (CCIR) located 
on the 10th floor of Barnes-Jewish Hospital at Washington University School of Medicine. 
The location allows outpatients and inpatients to undergo research-related imaging protocols 
in a safe imaging environment. The CCIR facility has complete clinical monitoring and 
resuscitation equipment including a fully supplied adult "crash cart” with a defibrillator as 
well as shielded patient uptake rooms with a television and warm blankets for patient comfort.  
A PET-certified registered nurse or CCIR PET technologist will administer 
radiopharmaceuticals.   
For women of child-bearing potential, a urine pregnancy test will be conducted in the CCIR 
prior to the imaging procedures.  Women who are pregnant or breast-feeding will not be 
eligible to participate in the study. 
f. Scanner Procedures 
The preferred scanner for F 18 T807 imaging is the PET/MR; however, in the event that 
there are technical difficulties or scanner availability issues, there will be the option to 
conduct the scans on any of the following scanners:  
i) On the Siemens model ECAT HRplus 962 PET scanner (stand-alone PET scanner) 
(located in Barnes-Jewish Hospital, West Pavilion, Neurology and Neurosurgery 
Intensive Care Unit (NNICU) Suite 10400) for the PET scans:  A NeuroShield 

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(Scanwell Systems) will be used to reduce random and scattered coincidences 
originating from extracranial radioactivity. A softened thermoplastic mask with enlarged 
eyeholes will be placed over the head and secured. After hardening, the mask will help 
minimize head motion. The participant will be positioned in the scanner such that the 
cantho-meatal line is approximately 1.0 cm above, and parallel to, the lowest imaging 
plane. A transmission scan will be obtained to correct attenuation. The participant will 
be asked to close their eyes. The room will be darkened and all noise minimized.  A 5-
10 minute transmission scan will be obtained for attenuation correction.  The subject 
will rest with eyes closed during the scan.  
ii) On the Siemens Biograph 40 PET/CT scanner (located in the Center for Clinical 
Imaging Research (CCIR), Barnes-Jewish Hospital, West Pavilion) for the PET scans:  
A softened thermoplastic mask with enlarged eyeholes will be placed over the head and 
secured.  After hardening, the mask will help minimize head motion. The subject will be 
positioned in the PET scanner such that the cantho-meatal line is approximately 1.0 cm 
above, and parallel to, the lowest imaging plane. A three-second X-ray Topogram will 
be acquired in the lateral plane to visualize the head and determine the exact scan 
position.  Prior to the PET scan, a spiral CT (Computed Tomography) scan will be 
performed for attenuation correction at the low dose CT setting of 37.5 mAs (which is 
25 effective mAs).  For the T807 scanning protocol Option 1 (PET acquisition from 0-
105 minutes with option for break after the first 60 minutes), a second CT may be 
acquired after the break, if a break is taken.  To minimize any possible variations in 
regional blood flow and initial tracer uptake, the subject will be asked to close their 
eyes.  The subject will rest with eyes closed during the scan.  
For purposes of attenuation correction CT scanning and in accordance with FDA 
recommendations released July 2009, participants will be questioned by the PI or PI’s 
designee before scanning about implanted medical devices or pumps.   The MRI 
screening form includes the question “Do you wear or have an implantable medical 
device such as a pacemaker or a drug pump?  
Yes   
No”.  This questionnaire will 
be signed and dated by the participant and kept in the participant’s study records.   In 
addition, the topogram will be checked prior to start of the CT attenuation scan.  If the 
participant has an implanted medical device or medicine pump, the participant will be 
advised about possible malfunction of such devices that could possibly be related to the 
attenuation CT scan.  It will be emphasized that this is a rare occurrence.  As with any 

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research protocol the subject will make the final decision whether or not to participate 
after appropriate discussion with family/friends as desired. 
iii) On the Siemens mMR PET/MR scanner (located in the Center for Clinical Imaging 
Research (CCIR), Barnes-Jewish Hospital, West Pavilion) for PET scans:  A softened 
thermoplastic mask with enlarged eyeholes may be placed over the head and secured.  
After hardening, the mask will help minimize head motion. The subject will be 
positioned in the scanner bed such that the cantho-meatal line is approximately 1.0 cm 
above, and parallel to, the lowest imaging plane. A three-second X-ray Topogram will 
be acquired in the lateral plane to visualize the head and determine the exact scan 
position.  A brief (less than 1 minute) CT scan may also be conducted on the PET/CT 
scanner for attenuation correction. 
iv) On the Siemens mMR PET/MR scanner (located in the Center for Clinical Imaging 
Research (CCIR), Barnes-Jewish Hospital, West Pavilion) for the MRI scan:  The MR 
system is a 3.0T whole body MRI system. All basic sequences and many sequences in 
development are compatible with this system. Features include: 60 cm system bore/50 
field of view and an integrated MR gradient coil. Maximum amplitude for all three 
gradient axes is 45 mT/m and slew rate is 200 T/m/s. Standard PET-compatible Tim® 
(Total imaging matrix) head and body phased array coils compatible with the Siemens 
Verio are available for use.  The MRI scan may be conducted simultaneously as the 18F-
FDG PET scan.  
v) On the Siemens Trio 3 Tesla scanner (located in the Center for Clinical Imaging 
Research (CCIR), Barnes-Jewish Hospital, West Pavilion) for the MRI scan.  The MR 
system is a 3.0T whole body MRI system. All basic sequences and many sequences in 
development are compatible with this system. 
vi) On the Siemens MAGNETOM Skyra 3 Tesla scanner (located in the Center for 
Advanced Medicine (CAM), Barnes-Jewish Hospital, West Pavilion) for the MRI scan.  
The MR system is a 3.0T whole body MRI system. All basic sequences and many 
sequences in development are compatible with this system. 
g. Neuropsychometric Assessments 
Participants will undergo cognitive and psychological assessments.  This will take 
approximately 2 hours to complete.  The following assessments will be conducted: 

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i)             Hopkins Verbal Learning Test 
ii)             Trailmaking Parts A and B 
iii)             Digit-Symbol Substitution Task 
iv)             Letter-Number sequencing 
v)             Wisconsin Card Sorting Test – 64 card version  
vi)             FAS Test 
vii)            Category Fluency 
viii) 
Action Fluency 
ix)             Stroop Interference Test 
x)             Brief Visuospatial Memory Test – Revised             
xi)             Boston Naming Test  
xii)            Mini Mental Status Examination 
xiii) 
Digit Span              
xiv) 
Continuous Performance Task              
xv)             Montreal Cognitive Assessment  
xvi) 
Frontal Systems Behavior Scale  
xvii) 
Logical Memory Test 
xviii) 
Ohio State University Traumatic Brain Injury Identification Method 
 
h. Follow-up 
A follow-up phone call to the participant will be conducted within 2 or 3 business days of 
the F 18 T807 imaging visit, but not before 48 hours post-injection, to confirm participant 
well-being and to collect information about any new adverse events. 
i. 
Analytic Plan 
The primary goal of this study is to perform and analyze F 18 T807 tau PET imaging in a 
well-characterized human cohort.  Data generated by this pilot study will be used to 
generate power calculations, aims, and hypotheses for NIH grant applications.  Because of 
the novel nature of this project, a power calculation cannot be performed at this time.  We 
will collaborate with the Knight ADRC Biostatistics Core to conduct extensive exploratory 
analyses to generate novel hypotheses for future testing. For example, we will correlate each 
imaging modality (MRI volumetrics, PET amyloid imaging, F 18 T807 PET imaging) from 
each matched FreeSurfer region, and locate the combinations of modalities and regions that 
best correlate with cognitive performance. 

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7. 
Informed Consent 
All participants will undergo written informed consent prior to any study procedures. 
Participants are interviewed over the phone to determine their eligibility (with a pre-screening 
assessment) and interest in participation. Participants that appear to meet the entrance criteria 
are given a more detailed explanation of the protocol’s procedures including a description of the 
protocol, the risks along with procedures to minimize these risks and the participants’ rights and 
responsibilities. The participants will be mailed or given a copy of the informed consent so that 
they can discuss participation with their private physician or family.  If the participant wishes to 
participate, the informed consent is signed prior to imaging procedures.  Participants are 
specifically told that they may withdraw consent for participation at any time without adversely 
affecting their medical care.   
 
Participants will be reimbursed for their participation in the imaging studies.  Participants will 
be asked to provide their social security number (SSN) in order for us to reimburse them. 
Participants will be advised that they may choose to participate without being reimbursed if they 
do not wish to provide their social security number (SSN) for this purpose.  They will also need 
to provide their address because the reimbursement for their study participation will be mailed 
to them. Once a check is issued, it will take up to eight weeks for the check to arrive at the 
address the subject provided.  If the participant’s social security number is obtained for 
reimbursement purposes only, it will not be retained for research purposes.    
 
8. 
Procedures for Maintaining Confidentiality 
a. Data Security 
All data obtained from research participation will be identified by a code number. All data 
will be kept in locked file cabinets and only made available to qualified research personnel. 
b. De-identification of Data  
Only code numbers will appear on any data and documents used for evaluation or statistical 
analysis.  No Protected Health Information (PHI) will be shared with others.  Publications 
emanating from this research will not identify individual patients.  HIPAA compliance will 
be enforced as per Washington University policy and HRPO approval.  Studies are done for 
research purposes only.  No services are billed to Medicare or Insurance Companies.  
Reports from patients’ records concerning research observations will not be available to 
outside medical facilities without the written consent of the subject. 

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De-identified study data will be maintained at Washington University.  This de-identified 
data may also be shared with other investigators doing research in similar fields such as 
Alzheimer disease, other neurological disorders or related brain diseases and abnormalities.  
These investigators may be at Washington University or at other research institutions.  This 
de-identified data may also be shared with large repositories for broad sharing with the 
research community.  If the participant’s research data is placed in one of these repositories, 
only qualified researchers who have received prior approval from individuals that monitor 
the use of the data, will be able to look at this information.  This de-identified study data 
will also be shared with the U.S. Food and Drug Administration.  Information from this 
research study has been or will be entered into a clinical trial databank that is maintained by 
the National Institutes of Health/National Library of Medicine.  It will not include 
information that can identify the subject. 
9. 
Assessment of Risks and Benefits 
a. Risks 
Potential risks are minimal as MRI and PET exclusion criteria and safety procedures will be 
applied. Participants with any metallic objects within their bodies will be screened using 
standard procedures at the Washington University Center for Clinical Imaging Research 
(CCIR) using criteria established and in place at Barnes-Jewish Hospital.  For pre-
menopausal women, a negative urine pregnancy test is required before radiopharmaceutical 
administration.  Specific risks for each of the study procedures are listed below.  The CCIR 
is a facility which provides both research and clinical imaging procedures.  The facility 
operates in compliance with the safety guidelines for imaging and for privacy as directed by 
the Health Insurance Portability and Accountability Act of 1996 (HIPAA), the Joint 
Commission on Accreditation of Healthcare Organization (JCAHO), the American College 
of Radiology (ACR), and the Nuclear Regulatory Commission (NRC).  PET 
radiopharmaceuticals used in the CCIR are produced in compliance with United States 
Pharmacopeia (USP) Chapter 823 standards. 

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i) Intravenous (I.V.) Catheter Placement  
(Likely) Participants may experience pain, bruising, and/or bleeding at the site of 
needle insertion for the intravenous catheter.  
(Rare) There is a rare risk of infection from a needle insertion. 
ii) Radiation  
(Likely) This study will expose the participant to radiation from the F 18 T807 PET 
scan and from the CT of the head.  The amount of radiation the participant will 
receive from one F 18 T807 scan, when averaged over the entire human body, is 
about 20% of the amount a person who works with radiation is allowed to have in 
one year. The risk from the radiation exposure in this study is too small to be 
measured. It is not a big risk when compared with other risks one takes every day 
(e.g., driving).  
iii) Scanner Related Risks  
(Less likely) Lying still in the scanner may produce some stiffness. Study staff will 
be nearby to stop the study in case the participant becomes uncomfortable and the 
exam will be terminated. (Rare) People with a fear of being in small, enclosed places 
may find this procedure uncomfortable. During the course of the exam, the 
technologists will be in communication with the participants and the study will be 
terminated if claustrophobia develops.  If the participant undergoes an MR scan, the 
technician will inquire about possible metallic objects inside the participant’s body.  
The MRI scanner produces a loud hammering noise.  A pair of earplugs may be 
placed in the participant’s ears to reduce the risk of hearing loss. Tattoos:  There are 
certain risks associated with undergoing an MRI scan if one has a skin tattoo.  These 
include risks associated with both cosmetic tattoos (eye-liner, lip-liner) and 
decorative tattoos.  These risks are greater if the tattoo was not applied 
professionally, or if the ink used in the tattoo is iron-based.   Associated risks include 
transient skin irritation, cutaneous swelling, or heating sensation.  In rare instances 
patients with decorative tattoos have had a primary or secondary burn occur at the 
tattoo site.  If the participant has a tattoo and decides to undergo the research MRI 
scan, we will offer the participant a cold, wet compress (washcloth) to put over the 
tattoo as a precautionary measure.  This decreases but does not eliminate the risk. 
There is a rare risk of malfunction of worn or implanted electronic medical devices 
with CT scanning.  The participant will be asked will be asked to advise the study 
investigator and research staff if he/she wears or has electronic medical devices 

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implanted such as a pacemaker or a drug pump.  It has been reported to the FDA that 
CT scan may cause a malfunction of electronic medical devices. 
 
iv) Risks associated with 18 F-AV-1451 
Less Likely:    Some participants are less likely to experience nausea, 
lightheadedness/dizziness, diarrhea, headache, and altered taste.  
Rarely:  Some participants may experience atrial fibrillation and transient ischemic 
attack. All reported events were mild in intensity and all subjects recovered from 
these events. Since 18F-AV-1451 is a new compound that is being studied in clinical 
trials, you may experience side effects that we do not know about yet.  
 
v) Risks from Additional Study Procedures 
18F- FDG (Optional) 
(Likely) This study will expose the participant to radiation from the18F-FDG PET 
scan and from the CT of the head.  The amount of radiation the participant will 
receive from one 18F-FDG PET scan, when averaged over the entire human body, is 
about 6% of the amount a person who works with radiation is allowed to have in one 
year. The risk from the radiation exposure in this study is too small to be measured. 
It is not a big risk when compared with other risks one takes every day (e.g., 
driving). 
 
vi) Questionnaires 

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Participants may experience emotional discomfort when answering some questions 
in the questionnaires (i.e. MRI and PET safety screening records; neuropsychometric 
assessment). If any particular question makes the participant uncomfortable, the 
participant may discuss its importance and the need to answer it with the specially-
trained interviewer. Participants have the right to refuse to answer any question for 
any reason.  If safety screening cannot be completed, then the imaging exams will be 
cancelled.  Participants may experience fatigue or embarrassment from the exercises 
of memory, movement, and attention. 
vii) Other Risks 
Participants may experience all or some of the risks listed above. There may also be 
unknown risks. The PI will answer any questions the participant has about these 
risks.  For participants who find the scanning session unpleasant, the session will be 
immediately terminated.  
b. Alternative Procedures 
If the participant is unable to undergo PET imaging with F 18 T807, there are no alternative 
procedures. 
 
10. 
Benefits 
Taking part in this research study will not benefit the subject directly.  An indirect benefit is 
contributing to biomedical research.  A possible benefit to society from this research is a better 
understanding of ALS that may eventually lead to improvements in medical care. 
 
11. 
Regulatory and Reporting Requirements 
a. Regulatory Compliance 
The Principal Investigator will conduct the protocol in adherence to institutional guidelines 
and in adherence with the Federal Food and Drug Administration (FDA), Department of 
Health and Human Services (DHHS), and the Code of Federal Regulations (CFR) procedures 
and requirements governing the use of investigational new drugs and the monitoring of serious 
adverse events (21 CFR 312). 
b. Adverse Events Monitoring and Documentation 
Each participant will be monitored for adverse events (AEs).  All AEs will be recorded.  The 
severity/intensity of the AE and its relationship to the administration of the study drug, F 18 

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T807, will be made by the Principal Investigator. Adverse events for purposes of this 
imaging trial are defined as any untoward medical occurrence in a subject who receives F 18 
T807.  The event does not necessarily have to be causally related to F 18 T807 to qualify as 
an adverse event.  An adverse event can be any unfavorable or unintended sign, symptom or 
disease temporally associated with the injection of F 18 T807, whether or not it is 
considered related to F 18 T807.  Signs and symptoms that are believed to be due to pre-
existing condition (started prior to dose of study medication) will not be recorded, unless 
there is an increase in frequency or severity.    
For the purposes of this study, untoward medical occurrences will be considered associated 
with the use of F 18 T807, and thus reported as adverse events, if they occur within 48 hours 
after F 18 T807 administration.  Adverse experiences that occur after administration but 
outside the 48 hour reporting window will not be reported unless the investigator believes 
they are attributable to the drug.  
In order to capture possible adverse effects of trial participation, trial-emergent adverse 
events will also be recorded as an untoward medical occurrences occurring during the trial 
period but not during the 48 hour window following the administration of F 18 T807.  The 
trial period will be defined as beginning with the signing of consent and ending 48 hours 
after the last study procedure, including (but not limited to) MR imaging, FDG PET scan, 
florbetapir F 18 PET scan, and lumbar puncture.    
Intensity/severity of an AE will classified as: (1) Mild: A mild adverse event is an adverse 
event, usually transient in nature and generally not interfering with normal activities; or (2) 
Moderate: A moderate adverse event is an adverse event that is sufficiently discomforting to 
interfere with normal activities; or (3) Severe: A severe adverse event is an adverse event 
that incapacitates the subject and prevents normal activities. Note that a severe event is not 
necessarily a serious event. Nor must a serious event necessarily be severe. 
c. Serious Adverse Event (SAE)  
An SAE is an AE that results in one of the following outcomes or constitutes one of the 
following events:  
• Death;  
• Initial or prolonged inpatient hospitalization;  
• A life-threatening experience (that is, immediate risk of dying);  

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• Persistent or significant disability/incapacity;  
• Congenital anomaly/birth defect;  
• Considered significant by the investigator for any other reason.  
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious adverse drug events when, based upon 
appropriate medical judgment, they may jeopardize the patient and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. 
d. Reporting of Serious Adverse Events 
1.  To Washington University’s Institutional Review Board:  
Within 24 hours of becoming aware of a serious adverse event (SAE), the study team will 
report the SAE to Washington University’s Institutional Review Board, the Human 
Research Protection Office (HRPO). Serious adverse events must be serious, unexpected, 
and reasonably related to the research.  Events which do not meet the requirements for SAE 
reporting will be reviewed by the Principal Investigator and documentation of the fact that 
the event does not meet SAE reporting requirements will be maintained in the participant’s 
chart. 
Serious adverse events occurring after a participant receives a dose of investigational 
product will be collected until 48 hours after the dosing of the investigational product, 
regardless of the investigator’s opinion of causation. Therefore, SAEs that occur later than 
48 hours after the dosing of the investigational product will not be recorded unless the 
investigator feels the events were related to the investigational product or a protocol 
procedure.  
If a participant experiences an SAE after signing informed consent, but prior to receiving 
investigational product, the event will not be reported unless the investigator feels the event 
may have been caused by a protocol procedure. Previously planned (prior to signing the 
ICF) surgeries will not be reported as SAEs unless the underlying medical condition has 
worsened during the course of the study. 
2.  To the U.S. Food and Drug Administration: 
The Sponsor-Investigator of this IND will comply with the FDA regulations as well as Title 
21 of the Code of Federal Regulations, by adhering to the following: 

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i) Report any unexpected fatal or life-threatening suspected adverse reactions to the FDA no 
later than 7 calendar days after initial receipt of the information [21 CFR 312.32(c)(2)].  
All 7-day reports will be submitted by telephone or fax. 
ii) Report any (1) serious, unexpected suspected adverse reactions, (2) findings from other 
clinical, animal, or in-vitro studies that suggest significant human risk, and (3) a clinically 
important increase in the rate of a serious suspected adverse reaction to the FDA and to all 
sub-investigators no later than 15 calendar days after determining that the information 
qualifies for reporting [21 CFR 312.32(c)(1)].  All 15-day reports will be submitted in 
paper format. 
iii) All documentation will be included in the IND Annual Report.  Modifications to the 
informed consent will be made if deemed necessary. Submitting annual progress reports 
within 60 days of the anniversary of the date that the Exploratory IND went into effect 
(the date clinical studies were permitted to begin) [21 CFR 312.33]. 
iv) Reporting to the FDA. All reports will be submitted to the FDA at the following address:  
Division of Medical Imaging Products 
Center for Drug Evaluation and Research 
U.S. Food and Drug Administration 
5901-B Ammendale Road  
Beltsville, MD 20705-1266 
FAX: 1-800-FDA-0178 
 
3.  To Avid Radiopharmaceuticals/Eli Lilly: 
Because the IND under which this study is conducted (IND 123,119) cross-references Avid 
Radiopharmaceutical’s IND 119,863, the study team shall notify Avid/Eli Lilly within 
twenty-four (24) hours of receiving notification of any serious adverse event experienced by 
a patient participating in the Study and receiving F 18 T807.  For purposes of this 
requirement, “serious” means:  (1) death; (2) in-patient hospitalization or prolonged 
hospitalization; (3) life-threatening; (4) persistent or significant disability or incapacity; (5) 
congenital anomaly or birth defect; Johor (6) other serious events that may jeopardize the 
patient and may require medical or surgical intervention to prevent one of the other five 
listed outcomes.  Serious adverse events may be reported via one of the following: 
i) Fax: 317-453-3402 
ii) Toll-free fax: 866-644-1697 

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iii) MAILINDATA_GSMTINDY@LILLY.COM 
 
 
e. Data Safety Monitoring (DSM) Reporting 
Safety data will be reviewed by the Principal Investigator and the research team as the 
information becomes available. An annual report will be submitted to Washington 
University’s Institutional Review Board (IRB).  This report will include the protocol title, 
IRB protocol number, the number of participants enrolled to date, statement of about study 
status, description of problems, description of any significant changes to the study design 
(previously approved by the IRB), and any participant experiences.  All pertinent information 
will be provided in the FDA Annual Report. 
f. Protocol Deviations 
All efforts will be made to follow the protocol as specified above.  In the event a situation 
occurs which requires deviation from this protocol, (i.e., less than expected tracer production, 
problems with the scanner, participants unable to tolerate imaging) the Principal Investigator 
will have final authority over whether or not a study is prematurely completed.  All protocol 
deviations will be documented and maintained in the participant’s research chart. Deviations 
such as less than expected tracer production can be accounted for during data analysis and 
will not necessarily result in cancellation of the scan. In the event of any deviations from the 
investigational plan that affects the life or physical well-being of a participant in any 
emergency, the Investigator will notify the IRB. Such notice will be submitted as soon as 
possible, but in no event later than 5 working days after the emergency occurred, except in 
such an emergency where prior approval by the sponsor-investigator is required for changes 
in or deviations from a plan, and if these changes or deviations may affect the scientific 
soundness of the plan or the rights, safety, or welfare of human rights, safety, or welfare of 
human subjects.  In this case, the FDA and IRB will be notified as required per the 
sponsor/investigator responsibilities outlined in 21 CFR 312. 
 
12. 
Case Report Forms 
Case Report Forms (CRFs) will be used to document eligibility criteria, demographic 
information, pregnancy test results, administration of radiopharmaceuticals, imaging visit 
sessions, telephone contact 2-3 days post-T807 injection, adverse events and serious adverse 
events, and record of contact with participants. 
 

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13. 
Record Archives 
As set forth by 21 CFR 312.57, records and reports will be retained for 2 years after a marketing 
application is approved for the drug; or if an application is not approved for the drug, until 2 
years after shipment and delivery of the drug for investigational use is discontinued and FDA 
has so been notified.   
 
 
 

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