[18F]FTC-146 PET/MRI in Healthy Volunteers and in CRPS and Sciatica

Participants are either pain free (control) or will be recruited based on established
criteria for sciatica or CRPS. A signed consent will be obtained from willing participants.

For the PET/MRI scan, the participants will be injected with [18F]FTC-146 intravenously.
After injection, simultaneous PET and MRI scans will be acquired using a hybrid PET/MRI
scanner. Throughout scanning, participants will be monitored for blood pressure, temperature,
heart rate and pulse oximetry. Participants will be asked to void their bladder as frequently
as they can to reduce radiation exposure. Following the scan, participants will be contacted
to check for adverse drug events, and any events will be recorded in the case report.

Evidence in the literature points strongly toward an involvement of S1 receptors in nervous
system inflammation, which is known to be an important biologic disease/disorder mechanism
for maintenance and perpetuation of chronic pain.

The main purpose of this research study is to image and identify activated pain pathways in
human subjects using [18F]FTC-146 PET/MRI.

Inclusion Criteria:

General:

- At least 18 years of age

- Either male or female

Sciatica:

- History of pain shooting down a leg below the knee, to the foot or toes

- Visual analog scale (VAS) at enrollment of >4 with leg pain greater in intensity than
the back pain

- Focal disc herniation on MRI correlating with radicular symptoms defined as pain or
paresthesias into the leg.

- Examination with correlating radicular signs defined as any of the following:

- pain reproduction with straight-leg-raising (pain shooting down the leg with less than
60 degrees elevation)

- radicular pattern sensory changes (such as numbness or paresthesias) in the same area
as pain

- signs of radiculopathy (weakened hallux extension and/or Achilles tendon reflex)

- The above inclusion criteria can be met OR individuals who have been determined to
have a very high clinical suspicion of having Sciatica as determined by the referring
pain specialist can be included. This suspicion will be documented in the patient's
medical record.

CRPS:

- Disease duration of 6 months or longer

- Continuing pain, which is disproportionate to any inciting event

- Must report at least one symptom in three of the four following categories:

1. Sensory: Reports of hyperesthesia and/or allodynia

2. Vasomotor: Reports of temperature asymmetry and/or skin color changes and/or skin
color asymmetry

3. Sudomotor/Edema: Reports of edema and/or sweating changes and/or sweating
asymmetry

4. Motor/Trophic: Reports of decreased range of motion and/or motor dysfunction
(weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)

- Must display at least one sign at time of evaluation In two or more of the following
categories:

1. Sensory: Evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch
and/or temperature sensation and/or deep somatic pressure and/or joint movement)

2. Vasomotor: Evidence of temperature asymmetry ( >1°C) and/or skin color changes
and/or asymmetry

3. Sudomotor/Edema: Evidence of edema and/or sweating changes and/or sweating
asymmetry

4. Motor/Trophic: Evidence of decreased range of motion and/or motor dysfunction
(weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)

- There is no other diagnosis that better explains the signs and symptoms

- For research purposes, diagnostic decision rule will be at least one symptom in all
four symptom categories and at least one sign (observed at evaluation) in two or more
sign categories.

- The above inclusion criteria can be met OR individuals who have been determined to
have a very high clinical suspicion of having CRPS as determined by the referring pain
specialist can be included. This suspicion will be documented in the patient's medical
record.

Exclusion Criteria:

General:

- Another active disorder which could explain the symptoms in the opinions of the
investigator

- Failure to give informed consent

- Presence of MRI-incompatible materials/devices

- Any medication that may affect pain or 18F-FTC-146 uptake or adverse drug interactions
with steroids or amino amide local anesthetics (e.g. lidocaine, bupivacaine,
ropivacaine)

- Pregnant or nursing

- Ongoing menstrual period

- Severe comorbid conditions

- Unable to read or complete questionnaires in English

- Any other condition, which in the opinion of the investigator would impede compliance
or hinder completion of the study

Sciatica:

- Any condition that may interfere with interpretation of 18F-FTC-146 uptake in the
region of the pelvis, thighs or lower spine including, but not limited to,

1. Spinal, hip or pelvic surgery or prosthesis

2. Cancer

3. Radiation therapy

4. Autoimmune disorders

5. Current infections

6. Inability to void bladder completely, such as in prostatic enlargement

7. Any urinary retention, such as in outlet obstruction, hydronephrosis etc.

8. Cauda equina syndrome

9. Developmental spinal deformities

10. Scoliosis >20 degrees

11. Spondylolysis

12. Vertebral fractures

13. Inflammatory spondylopathy

14. Prior lumbar surgery

CRPS:

- Presence of current or past pulmonary, hepatic, renal disease, arthritis,
hematopoietic, and neurological diseases not related to CRPS.