Primary Objective: Development of a tracer kinetic model for tracers [11C]DPA-713 and [18F]PEG-Folate.Secondary Objectives: 1. Development of a static imaging protocol and a validated simplified measure for quantification of uptake of tracers [11C]…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Development of a tracer kinetic model for tracers [11C]DPA-713 and
[18F]PEG-Folate.
Secondary outcome
1. Development of a static imaging protocol and a validated simplified measure
for quantification of uptake of tracers [11C]DPA-713 and [18F]PEG-Folate in
arthritic joints in RA patients.
2. Comparison of the static and kinetic model, leading to simplification of
protocols for routine clinical studies.
Background summary
Rheumatoid arthritis (RA) is a chronic systemic connective tissue disease that
primarily affects the synovial joints. The inflammation is usually chronic, and
may cause progressive destruction of bone and cartilage, eventually leading to
loss of function. Recent international guidelines stress the importance of
starting effective treatment as early as possible. A new diagnostic tool for
early diagnostics and therapy monitoring could greatly reduce permanent
physical damage.
Positron emission tomography is a highly sensitive imaging technique that
enables monitoring of disease activity and therapeutic effects. PET tracers can
be specifically target to cells or molecules of interest. The macrophage has
been shown to be a promising target for both early diagnostics and therapy
monitoring, because of its infiltration in synovium from the early development
of RA onwards. Studies by our research group have shown that macrophage PET
imaging can visualize inflammatory activity in rheumatoid arthritis (RA), even
at subclinical level. The potential of PET to predict therapeutic outcome of RA
treatment has also been demonstrated.
Previously, our group studied the tracer [11C]-R-PK11195, which binds to
peripheral benzodiazepine receptors (TSPO) on macrophages, and has shown to
successfully visualize inflammatory lesions. This tracer accumulated
significantly in clinically inflamed joints when compared to healthy ones.
However, the relatively high level of background binding of [11C]-(R)-PK11195
in peri-articular tissues limited detection of more subtle arthritis. This
finding has stimulated development of alternative macrophage tracers for
arthritis imaging that display more favourite target-to-background signals in
arthritic joints.
In subsequent pre-clinical and clinical proof of concept studies, we have shown
that [11C]DPA713 and [18F]PEG Folate are promising novel candidate macrophage
tracers to image arthritis activity in RA. A new generation TSPO tracer, is
[11C]DPA-713. Is a new generation TSPO tracer that showed higher absolute
uptake in arthritic joints and higher target-to-background ratios as compared
to [11C]PK11195. [18F]PEG Folate targets the *-isoform of the folate receptor
(FR*), which is expressed on activated macrophages. Both pre-clinical and
clinical feasibility data in RA demonstrated very low background uptake and
clear targeting of arthritic joints. The collected proof of concept data did
not allow selection of one tracer above the other for further development
towards clinical application studies. [11C]DPA713 has an interesting profile
for therapy monitoring of RA treatment as C-11 has a very short half-life (20
min) and hence a low radiation burden which allows for repetitive scanning.
[18F]PEG Folate seems to be particularly suited for early diagnostics of both
articular and extra-articular diseases activity of RA because of low background
uptake in the whole body.
Study objective
Primary Objective: Development of a tracer kinetic model for tracers
[11C]DPA-713 and [18F]PEG-Folate.
Secondary Objectives:
1. Development of a static imaging protocol and a validated simplified measure
for quantification of uptake of tracers [11C]DPA-713 and [18F]PEG-Folate in
arthritic joints in RA patients.
2. Comparison of the static and kinetic model, leading to simplification of
protocols for routine clinical studies.
Study design
A monocenter, prospective observational study in 6 patients with active
rheumatoid arthritis. [11C]DPA-713 and [18F]PEG-Folate uptake will be measured
quantitatively. Accuracy of blood and plasma activity concentration, plasma
metabolite measurements derived from arterial and venous samples as well as the
reliability of using Image Derived Input Functions (IDIF) for quantifiction of
[11C]DPA-713 and [18F]PEG-Folate kinetics will be tested. Dynamic PET and CT
scanning will be performed in two separate sessions on one day,
first[11C]DPA-713, and subsequently (after * 5 half-lives of C-11)
[18F]PEG-Folate.
Intervention
Not applicable.
Study burden and risks
- The total radiation burden will be about 8.9 mSv, therefor staying under the
limit of 10 mSv.
- Venous and arterial punction with risk of local bruises.
- Very small chance of allergic reaction to PET tracer
De Boelelaan 1117
Amsterdam 1081HV
NL
De Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
* Men and women, * 18 years of age.
* Diagnosis of rheumatoid arthritis according to the 1987 revised criteria of the American Rheumatism Association (ARA) and/or the 2010 ACR/EULAR Rheumatoid Arthritis Classification Criteria.
* Patients with obvious clinical arthritis activity assessed by a physician, in at least 1 hand, wrist of knee joints.
* Treatment with disease modifying anti-rheumatic drugs (DMARDS), biologics and oral corticosteroids up to 10 mg daily is allowed. Non-steroidal anti-inflammatory drugs (NSAID) is permitted, provided that there is a stable dose for at least 1 month.
* Patients must be able to adhere to the study appointments and other protocol requirements.
* Patients must be capable of giving informed consent and the consent must have been obtained prior to the study related procedures.
Exclusion criteria
* Use of intramuscular or intravenous corticosteroids within 4 weeks prior to screening.
* Treatment with any investigational drug within the previous 3 months.
* Pregnancy or breast-feeding
* Anemia (Hemoglobine <6.0 mmol/L)
* Renal insufficiency (GFR <30 mL/min/1.73m2)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-004423-22-NL |
| CCMO | NL59690.029.16 |