DOSAGE AND ADMINISTRATION
Radiation Safety - Drug Handling
Neuraceq is a radioactive drug and should be handled with
appropriate safety measures to minimize radiation exposure during
administration [see WARNINGS AND PRECAUTIONS]. Use waterproof gloves and
effective shielding, including lead-glass syringe shields when handling and
administering Neuraceq. Radiopharmaceuticals, including Neuraceq, should only
be used by or under the control of physicians who are qualified by specific
training and experience in the safe use and handling of radioactive materials,
and whose experience and training have been approved by the appropriate
governmental agency authorized to license the use of radiopharmaceuticals.
Recommended Dosing And Administration Instructions
The recommended dose of Neuraceq is 300 MBq (8.1 mCi),
maximum 30 mcg mass dose, administered as a single slow intravenous bolus (6
sec/mL) in a total volume of up to 10 mL.
- Inspect the radiopharmaceutical dose solution prior to
administration and do not use it if it contains particulate matter
- Use aseptic technique and radiation shielding to withdraw
and administer Neuraceq solution.
- Measure the activity of Neuraceq with a dose calibrator
immediately prior to injection.
- Do not dilute Neuraceq
- The injection must be intravenous in order to avoid
irradiation as a result of local extravasation, as well as imaging artifacts.
Verify patency of the indwelling catheter by a saline test injection prior to
administration of Neuraceq.
- An injection (6 sec/mL) into a large vein in the arm is
recommended, followed by a saline flush of approximately 10 mL.
- Dispose of unused product in a safe manner in compliance
with applicable regulations
Image Acquisition Guidelines
Acquire PET images over 15 to 20 minutes starting 45 to
130 minutes after Neuraceq injection. Keep the patient supine with the head
positioned to center the brain, including the cerebellum, in the PET scanner
field of view. Reduce head movement with tape or other flexible head restraints
if necessary. Reconstruction should include attenuation correction with
resulting transaxial pixel sizes between 2 and 3 mm.
Image Display And Interpretation
Neuraceq images should be interpreted only by readers who
successfully complete Electronic Media-or In-Person Training provided by the
manufacturer [see WARNINGS AND PRECAUTIONS]. The objective of Neuraceq
image interpretation is to estimate β-amyloid neuritic plaque density in
brain gray matter, not to make a clinical diagnosis. Image interpretation is
performed independently of a patient's clinical features and relies upon the
recognition of image features in certain brain regions.
Image Display
PET images should be displayed in the transaxial
orientation using gray scale or inverse gray scale. The sagittal and coronal
planes may be used for additional orientation purposes. CT or MR images may be
helpful for anatomic reference purposes. However, visual assessment should be
performed using the axial planes according to the recommended reading
methodology.
Image Interpretation
Interpretation of the images is made by visually
comparing the activity in cortical gray matter with activity in adjacent white
matter. Regions displayed in the PET images which "anatomically" correspond to
white matter structures (e.g., the cerebellar white matter or the splenium)
should be identified to help the readers orient themselves. Images should be
viewed and assessed in a systematic manner, starting with the cerebellum and
scrolling up through the lateral temporal and frontal lobes, the posterior
cingulate cortex/precuneus, and the parietal lobes. For a gray matter cortical
region to be assessed as showing "tracer uptake", the majority of slices from the
respective region must be affected.
For each patient, the PET image assessment is categorized
as either “β-amyloid-positive” or “β-amyloid-negative”. This
determination is based on the assessment of tracer uptake in the gray matter of
the following four brain regions: the temporal lobes, the frontal lobes, the
posterior cingulate cortex/precuneus, and the parietal lobes; according to the
following "rules for assessment" [see WARNINGS AND PRECAUTIONS]:
β-amyloid negative -tracer uptake
(i.e., signal intensity) in gray matter is lower than in white matter in all
four brain regions (no β-amyloid deposition)
β-amyloid positive -smaller area(s) of
tracer uptake equal to or higher than that present in white matter extending
beyond the white matter rim to the outer cortical margin involving the majority
of the slices within at least one of the four brain regions (“moderate”
β-amyloid deposition), or a large confluent area of tracer uptake equal to
or higher than that present in white matter extending beyond the white matter
rim to the outer cortical margin and involving the entire region including the
majority of slices within at least one of the four brain regions (“pronounced”
β-amyloid deposition). There is no known clinical or histopathologic correlation
distinguishing “moderate” from “pronounced” β-amyloid deposition.
Examples of positive and negative scans for each of the
four brain regions are illustrated in Figure 1.
Figure 1 :Axial view of negative (top row) and
positive (bottom row) Neuraceq PET scans
 |
Cerebellum: A contrast between the white matter (arrows) and gray
matter is seen in both negative and positive scans. Extracerebral tracer uptake
in scalp and in the posterior sagittal sinus (arrowhead) can be seen. Lateral
temporal lobes: Spiculated or “mountainous” appearance of the white matter
(arrows) is seen in the negative scan, and radioactive signal does not reach
the outer rim of the brain (dashed line) due to lower tracer uptake in the gray
matter. The positive scan shows a “plumped”, smooth appearance of the outer
border of the brain parenchyma (dashed line) due to tracer uptake in the gray
matter. Frontal Lobes: Spiculated appearance of the white matter in the
frontal lobes (arrows) is seen in the negative scan. The positive scan shows
the tracer uptake in these regions has a “plumped”, smooth appearance due to
the increased gray matter signal (dashed line). Posterior
cingulate/precuneus: Adjacent and posterior to the splenium (arrow), these
regions appear as a hypo-intense “hole” (circle) in the negative scan, whereas
this hole is “filled-up” (circle) in the positive scan. Parietal lobes: In
the negative scan, the midline between the parietal lobes can be easily
identified (long arrow); white matter has a spiculated appearance (short arrow)
with low signal near the outer rim of the brain (dashed line). In the positive
scan, the midline between the parietal lobes is much thinner. The cortical
areas are “filled-up” and are smooth in appearance as tracer uptake extends to
the outer rim of the brain.
Some scans may be difficult to
interpret due to image noise, atrophy with a thinned cortex, or image blur. If
a coregistered computerized tomography (CT) image is available, the CT image
may be used to clarify the relationship of the Neuraceq uptake and the gray
matter anatomy.
Radiation Dosimetry
The estimated radiation absorbed doses for adults from
intravenous injection of Neuraceq are shown in Table 1.
Table 1 : Estimated Radiation Absorbed Doses from
Intravenous Injection of Neuraceq
Organ/Tissue |
Mean Absorbed Radiation Dose per Unit Administered Activity [mcGy/MBq] |
Adrenals |
13 |
Brain |
13 |
Breasts |
7 |
Gallbladder Wall |
137 |
Heart Wall |
14 |
Kidneys |
24 |
Liver |
39 |
Lower Large Intestine-Wall |
35 |
Lungs |
15 |
Muscle |
10 |
Osteogenic Cells |
15 |
Ovaries |
16 |
Pancreas |
14 |
Red Marrow |
12 |
Skin |
7 |
Small Intestine |
31 |
Spleen |
10 |
Stomach Wall |
12 |
Testes |
9 |
Thymus |
9 |
Thyroid |
8 |
Upper Large Intestine-Wall |
38 |
Urinary Bladder Wall |
70 |
Uterus |
16 |
Total Body |
11 |
Effective Dose (mcSv/MBq) |
19 |
The effective dose resulting
from a 300 MBq (8.1 mCi) administration of Neuraceq in adult subjects is 5.8
mSv. The use of a CT scan to calculate attenuation correction for
reconstruction of Neuraceq images (as done in PET/CT imaging) will add
radiation exposure. Diagnostic head CT scans using helical scanners administer
an average of 2.2 ± 1.3 mSv effective dose (CRCPD Publication E-07-2, 2007). The
actual radiation dose is operator and scanner dependent. Thus, the total
combined radiation exposure from Neuraceq administration and subsequent scan on
a PET/CT scanner is estimated to be 8 mSv.
HOW SUPPLIED
Dosage Forms And Strengths
Neuraceq is available in 30 mL
multi-dose vials containing a clear solution at a strength of 50-5000 MBq/mL
(1.4-135 mCi/mL) florbetaben F18 at EOS. At time of administration 300 MBq (8.1
mCi) are contained in up to 10 mL of solution for injection.
Neuraceq is supplied in a 30 mL
glass vial containing up to 30 mL of a clear solution at a strength of 50 to
5000 MBq/mL (1.4 to 135 mCi/mL) florbetaben F18 at EOS. Each vial contains
multiple doses and is enclosed in a shielded container to minimize external
radiation exposure.
Storage And Handling
Store Neuraceq at room temperature 25°C (77°F); excursions
permitted to 2°C to 42°C (36°F to 108°F).
The product does not contain a preservative. Store
Neuraceq within the original container or equivalent radiation shielding.
Neuraceq must not be diluted.
This preparation is approved for use by persons under
license by the Nuclear Regulatory Commission or the relevant regulatory
authority of an Agreement State.
Manufactured for Piramal Imaging, S.A., Route de l'Ecole
13, 1753 Matran Switzerland. Revised: Aug 2016