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RecruitingNCT04699747Updated Oct 7, 2026

Investigating the Utility of Demyelination Tracer [18F]3F4AP in Controls and Multiple Sclerosis Subjects

A Phase 1 interventional study of F-18 3F4AP in Multiple Sclerosis, sponsored by Massachusetts General Hospital. Recruiting at 1 site in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-10-07.

Sponsored by Massachusetts General Hospital · Phase 1, Interventional, and Basic science

From the registry’s dates

  • Started Mar 2021; still recruiting 5 years 6 months later.
Updated Oct 7, 2026Primary completion movedStudy completion movedGo to Updates ↓
Phase
Phase 1
Study type
Interventional
Enrollment
60
Allocation
Non-randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

Our overall objective is to obtain an initial assessment of the potential value of using [18F]3F4AP for imaging demyelinating diseases such as multiple sclerosis:

  • Aim 1) Assess the safety of [18F]3F4AP in healthy volunteers and subjects with multiple sclerosis (MS). Hypothesis 1: Administration of [18F]3F4AP will result in no changes in vitals or other adverse events.
  • Aim 2) Assess the pharmacokinetics of a bolus infusion of [18F]3F4AP in humans including healthy volunteers and MS patients. Hypothesis 2: the pharmacokinetics of [18F]3F4AP at the whole brain level will be similar in controls and MS subjects. The kinetics in demyelinated lesions will be slower than in healthy control areas.
  • Aim 3) Assess the reproducibility of [18F]3F4AP in humans. Hypothesis 3: the test/retest variability of [18F]3F4AP within the same subject will be lower than 10%.
  • Aim 4) Correlate MR brain images with [18F]3F4AP PET brain images. Hypothesis 4A: all the lesions seen on the MRI will show increased signal (VT or SUV) on the PET images. Hypothesis 4B: some of the lesions on the MRI will show increased signal (VT or SUV) on the PET but not all.
  • Aim 5) Correlate [18F]3F4AP PET signal with neuropsychological testing in people with MS. Hypothesis 5: increased PET signal (VT or SUV) will correlate with impaired Single Digit Modality Test (SDMT) scores.
  • Aim 6) Correlate [18F]3F4AP PET signal with EDSS score in people with MS. Hypothesis 6: increased PET signal (VT or SUV) will correlate with higher EDSS scores.
02

Conditions studied

  • Multiple Sclerosis

Keywords

  • Demyelination
  • Brain imaging
  • Positron Emission Tomography
  • Radiopharmaceutical
03

In context

Multiple Sclerosis

3,460 studies on the registry are indexed under Multiple Sclerosis; 661 are open to participants now.

This study's planned enrollment of 60 is above the median of 50 across 2,342 interventional studies indexed under Multiple Sclerosis.

Browse Multiple Sclerosis studies →

Lead sponsor

Massachusetts General Hospital is the lead sponsor of 2,536 studies on the registry; 446 are open to participants now.

Of its 214 completed or terminated interventional studies of FDA-regulated products, 161 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Subjects must be ≥18 and \<65 years of age;
  • Able to understand and provide informed consent prior to study procedures

Exclusion criteria

Exclusion Criteria:

  • Subjects with known structural brain disease (e.g. brain tumor or stroke);

  • Any contraindication to MRI and/or PET, including:

    • Subjects with life vest;
    • Subjects with implanted heart device (e.g. ICD, Pacemaker);
    • Subjects with metallic fragment or foreign body;
    • Subjects with other form of devices or prosthesis that are not MRI compatible, such as insulin pump, joint replacement, hearing aid, cochlear implant, permanent contraceptive devices, etc.;
    • Subjects with severe claustrophobia
    • Relative or absolute contraindication to Dotarem contrast:
  • history of renal disease including acute or chronic severe renal insufficiency (glomerular filtration rate \<60 mL/min/1.73m2);
  • history of diabetes mellitus, systemic lupus, multiple myeloma, nephrogenic systemic fibrosis, and other co-morbidities;
  • History of hypersensitive reactions to Dotarem and/or gadolinium contrast agent;
  • Radiation exposure exceeds current Radiology Department guidelines (i.e., 50 mSv in the prior 12 months);
  • Female subjects only: Positive serum pregnancy test, or lactating, or possibility of pregnancy cannot be ruled out prior to dosing;
  • Inability to provide written informed consent;
  • Any clinically significant acute or unstable physical or psychiatric condition, judged by the investigators based on medical history or screening physical examination, to be incompatible with the study;
  • Any physical or psychiatric condition judged by the investigators to be incompatible with the study, based on medical history or screening physical examination;
  • Abnormal results on blood tests judged by the investigators to be incompatible with the study.
05

Study design

Phase
Phase 1
Primary purpose
Basic science
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
60 participants (estimated)

Study arms

  • Experimental
    Multiple sclerosis

    F-18 3F4AP PET Scan

    Drug: F-18 3F4AP

  • Active comparator
    Healthy controls

    F-18 3F4AP PET Scan

    Drug: F-18 3F4AP

Interventions

  • DrugF-18 3F4AP

    Subjects will be injected once per imaging session (a maximum of 2 imaging sessions) with up to 10 mCi (±20%) of 18-F 3F4AP as a rapid intravenous bolus (within 1 min).

    Also known as: [18F]3F4AP

06

What researchers measure

Primary outcomes

  1. Binding of 18-F 3F4AP in the brain of healthy volunteers and multiple sclerosis subjects

    Binding of the tracer will be quantified using volumes of distribution (VTs). Volume of distribution is the ratio of tracer concentration in tissue to plasma at equilibrium and will be determined using standard pharmacokinetic methods (Innis et al, J Cereb Blood Flow Metab. 2007; 27(9): 1533-1539).

    Time frame: Baseline

  2. Number of participants with adverse events related to tracer administration as assessed by CTCAE v4.0

    Determine number of participants adverse events related to tracer administration as assessed by CTCAE v4.0

    Time frame: 5 years

Secondary outcomes

  1. Binding of 18-F 3F4AP in brain lesions of multiple sclerosis subjects

    Binding of the tracer in the lesions will be quantified using volumes of distribution (VTs). Lesions will be delineated based on 3D FLAIR MRI using standardized methods.

    Time frame: Baseline

  2. Within-subject variability in healthy controls and multiple sclerosis subjects

    Within-subject variability (test/retest variability or TRV) of the VT in healthy volunteers and multiple sclerosis subjects

    Time frame: Retest within 3 months of baseline

07

Study locations

1 of 1 sites recruiting
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
    • Pedro Brugarolas, PhD · Contact · 617-643-4574
    Recruiting
08

References and documents

Publications

  • Tiss A, Michaelson NM, Russo AW, Ramos-Torres KM, Sun Y, DaSilva NE, Noel JM, Liu F, Gong K, Huang SY, Popko B, Baker S, Klawiter EC, Brugarolas P. First evaluation in multiple sclerosis using PET tracer [18F]3F4AP demonstrates heterogeneous binding across lesions. Eur J Nucl Med Mol Imaging. 2026 Jan;53(2):1125-1138. doi: 10.1007/s00259-025-07454-1. Epub 2025 Aug 5. PubMed 40759830 ↗

Individual participant data

Plan to share: No

09

Updates

1 registry update since Sep 25, 2026
Primary completion
Nov 30, 2026→Sep 30, 2028
Oct 7, 2026
Study completion
Nov 30, 2026→Sep 30, 2028
Oct 7, 2026
Show all 1 update
  1. Oct 7, 2026
    Primary completion Nov 30, 2026→Sep 30, 2028
    Study completion Nov 30, 2026→Sep 30, 2028
    + 4 other changes: index terms, verification date, oversight details and references

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT04699747
Lead sponsor
Massachusetts General Hospital
Responsible party
Pedro Brugarolas (Assistant Professor of Radiology, Massachusetts General Hospital) — Principal investigator
First posted
Jan 7, 2021
Start date
Mar 25, 2021
Primary completion
Sep 30, 2028 (estimated)
Completion
Sep 30, 2028 (estimated)
Last update
Oct 7, 2026

Study contacts

Pedro Brugarolas, PhD
Contact
pbrugarolas@mgh.harvard.edu
(617) 643-4574

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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