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CERETEC 500 MICROGRAMS KIT FOR RADIOPHARMACEUTICAL PREPARATION

Active substance(s): EXAMETAZIME / EXAMETAZIME / EXAMETAZIME

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Package leaflet: Information for the patient
Ceretec 500 micrograms kit for
radiopharmaceutical preparation
Exametazime
(called Ceretec in this leaflet)
Read all of this leaflet carefully before you
are given this medicine because it contains
important information for you.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your
nuclear medicine doctor.
• If you get any side effects, talk to your nuclear
medicine doctor. This includes any possible side
effects not listed in this leaflet. See section 4.
What is in this leaflet:
1. What Ceretec is and what it is used for
2. What you need to know before Ceretec is used
3. How Ceretec is used
4. Possible side effects
5. How Ceretec is stored
6. Contents of the pack and other information
1. What Ceretec is and what it is used for

Document: 1189056 GBR Version: 0

Ceretec is a radiopharmaceutical product for
diagnostic use only. It is used only to help identify
illness.
Ceretec is given before a scan and helps a special
camera see inside a part of your body.
• It contains an active ingredient called
‘exametazime’. This is mixed with another
ingredient called technetium’ before it is used.
• Once injected it can be seen from outside your
body by a special camera used in the scan.

• The scan can help your doctor see how much
blood is flowing through the brain. This may be
important to know after a stroke, if you have
fits or epilepsy, Alzheimer’s disease or a similar
type of dementia. It may also be used in people
who have migraine (headaches) or a brain
tumour.
• The scan can help your doctor investigate fever
when the reason for the fever is not known.
• The scan can also help your doctor investigate
sites of infection, such as in your abdomen
(the area around your stomach).
• Some other people are given this medicine to
see swelling (inflammation) in the bowel.
Your nuclear medicine doctor will explain which
part of your body will be scanned. The use of
Ceretec does involve exposure to small amounts of
radioactivity. Your doctor and the nuclear medicine
doctor have considered that the clinical benefit
of this procedure with the radiopharmaceutical
outweighs the risk of being exposed to these small
amounts of radiation.
Ask your nuclear medicine doctor if you have any
questions.
2. What you need to know before Ceretec is
used
Ceretec must not be used:
• If you are allergic (hypersensitive) to the active
ingredient or any other ingredients of this
medicine (listed in Section 6).
Warnings and precautions
Talk to your nuclear medicine doctor before using
Ceretec
• if the person who will be given this medicine is
a child.
• if you are pregnant or think you may be
pregnant.
• if you are breast feeding.
• if you are on a low sodium diet.

Before Ceretec administration you should:
Drink plenty of water before the start of the
examination in order to urinate as often as
possible during the first hours after the study.
Children and adolescents
Ceretec is not recommended for administration to
children.
Other medicines and Ceretec
Tell your nuclear medicine doctor who will
supervise the procedure if you are taking or have
recently taken or might take any other medicines,
since they may affect the way Ceretec works.
No medicines have been reported that affect
the way Ceretec works. But it is still best to tell
your doctor or nurse if you are taking any other
medicines.
Ceretec with food and drink
Your doctor may recommend that you drink
plenty of fluids and pass water (urinate) as often
as possible in the hours after the injection.
Pregnancy and breast-feeding
You must tell your nuclear medicine doctor before
you are given Ceretec if there is a possibility
you might be pregnant, if you have missed your
period or if you are breast-feeding. When in
doubt, it is important to consult your nuclear
medicine doctor who will supervise the procedure.
If you are pregnant
The nuclear doctor will only give this medicine
during pregnancy if a benefit is expected which
would outweigh the risk.
If you are breast-feeding
Do not breast-feed if you are given Ceretec. This
is because small amounts of ‘radioactivity’ may
pass into the mother’s milk. If you are breastfeeding, your nuclear medicine doctor may wait
until you have finished breast-feeding before

using Ceretec. If it is not possible to wait, your
nuclear medicine doctor may ask you to:
• stop breast-feeding for 12 hours, and
• use formula feed for your child, and
• express (remove) breast milk and throw away
the milk.
Your nuclear medicine doctor will let you know
when you can start breast-feeding again.
Driving and using machines
It is considered unlikely that Ceretec will affect
your ability to drive or to use machines. Ask your
nuclear medicine doctor if you can drive or use
machines after you have been given Ceretec.
Ceretec contains sodium: 1.77 mg per vial.
This may need to be considered for people on a
low sodium diet.
3. How Ceretec is used
There are strict laws on the use, handling and
disposal of radiopharmaceutical products.
Ceretec will only be handled and given to you by
professionals who are trained and qualified to use
it safely.
Administration of Ceretec and conduct of the
procedure
Dose
The nuclear medicine doctor supervising the
procedure will decide on the amount of Ceretec
to be used in your case. The doctor will choose
the smallest amount necessary to get the desired
information.
The amount to be administered usually
recommended for an adult ranges from 350 to
500 MBq for brain scintigraphy and 200 MBq for
in vivo localisation of technetium-99m-labelled
leucocytes. Megabecquerel (MBq) is the unit used
to express radioactivity
turn over ➤

Samples that will be required before you have
Ceretec
• A sample of your blood may be taken.
One injection is sufficient to carry out the scan
that your doctor needs.
If a sample of your blood has been taken it will be
mixed with a solution (containing Ceretec and the
ingredient called ‘technetium’) which will then be
given to you as an injection.
• Ceretec will always be used in a hospital or
clinic.
• Ceretec will be given to you by a specially
trained and qualified person
They will provide you with the necessary
information on the procedure.
Duration of the procedure
Your nuclear medicine doctor will inform you
about the usual duration of the procedure.

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After administration of Ceretec you should:
• urinate frequently in order to eliminate the
product from your body
The nuclear medicine doctor will inform you if
you need to take any special precautions after
receiving this medicine. Contact your nuclear
medicine doctor if you have any questions.
If you are given more Ceretec than you should
An overdose is unlikely because you will only
receive a single dose of Ceretec precisely
controlled by the nuclear medicine doctor
supervising the procedure. However, in the case
of an overdose, you would receive the appropriate
treatment.
If you have any further questions on the use of
this medicine, please ask your nuclear medicine
doctor who supervises the procedure.

4. Possible side effects

5. How Ceretec is stored

Like all medicines, this medicine can cause side
effects, although not everybody gets them.

You will not have to store this medicine. This
medicine is stored under the responsibility of the
specialist in appropriate premises. Storage of
radiopharmaceuticals will be in accordance with
national regulation on radioactive materials.
Hospital staff will ensure that the product is
stored and disposed of correctly and not used
after the expiry date stated on the label.
The following information is intended for
healthcare or medical professionals only.
• Keep this medicine out of the sight and reach of
children.
• Do not use this medicine after the expiry date
which are stated on the label after ‘EXP’.
• Store the reconstituted product below 25°C. do
not freeze or refrigerate
• The labelled product must be injected within
30 minutes of reconstitution

Allergic reactions
Tell your doctor straight away if you have an
allergic reaction when you are in hospital or a
clinic having the scan. The signs may include:
• skin rash or itching or flushing
• swelling of the face
• difficulty in breathing.
In more serious cases reactions may include:
• passing out (unconsciousness), feeling dizzy or
lightheaded.
If any of the side effects above happen after you
leave the hospital or clinic, you should go or be
taken straight to the casualty department of your
nearest hospital.
Other side effects include (frequency not
known):
• itchy lumpy rash
• headache
• feeling dizzy
• flushing
• feeling sick (nausea)
• being sick (vomiting)
• general feeling of being unwell, weak or tired
• unusual feelings of numbness, tingling, prickling
burning or creeping on skin.
This radiopharmaceutical will deliver low amounts
of ionising radiation with the least risk of cancer
and hereditary abnormalities.
Reporting of side effects
If you get any side effects, talk to your nuclear
medicine doctor. This includes any possible side
effects not listed in this leaflet. You can also
report side effects directly via the Yellow Card
Scheme at www.mhra.gov.uk/yellowcard.
By reporting side effects, you can help provide
more information on the safety of this medicine.

6. Contents of the pack and other information
What Ceretec contains
• The active ingredient is exametazime. Each
vial of Ceretec contains 500 micrograms of
exametazime.
• The other ingredients are stannous chloride
dihydrate and sodium chloride.
What Ceretec looks like and contents of the
pack
Ceretec is supplied as a kit for
radiopharmaceutical preparation. The kit contains
two or five vials. Not all pack sizes may be
marketed.
Each vial contains 500 micrograms of
exametazime.

Marketing
Authorisation Holder
GE Healthcare Limited
Amersham Place
Little Chalfont
Buckinghamshire
HP7 9NA
United Kingdom
Manufacturer
GE Healthcare AS
Nycoveien 1-2
0401 OSLO
Norway
This leaflet was
last revised in
March 2017
Marketing
Authorisation
UK: PL 00221/0126
Ceretec is a trademark
of GE Healthcare.
GE and the GE
Monogram are
trademarks of General
Electric Company.

GE Healthcare

PATIENT
INFORMATION

CeretecTM
500 micrograms kit for
radiopharmaceutical
preparation
Exametazime

1189056

1189056 GBR

PACKAGE LEAFLET: INFORMATION FOR HEALTHCARE PROFESSIONAL
1. NAME OF THE MEDICINAL PRODUCT
Ceretec 500 micrograms kit for radiopharmaceutical preparation.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each vial contains exametazime 500 micrograms.
Ceretec is reconstituted with Sodium Pertechnetate (99mTc) Injection
(not included in this kit) to prepare Technetium (99mTc) Exametazime
Injection.
Excipients with known effect
The product before reconstitution contains sodium: 1.77 mg/vial.
This needs to be taken into consideration for patients on a controlled
sodium diet.
For a full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Kit for radiopharmaceutical preparation.
A white powder.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
This medicinal product is for diagnostic use only.

After reconstitution with Sodium Pertechnetate (99mTc) Injection, the
product is indicated in adults for:
(1) Technetium (99mTc) Exametazime Injection is indicated for brain
scintigraphy. The product is to be used for the diagnosis of
abnormalities of regional cerebral blood flow, such as those
occurring following stroke and other cerebrovascular disease,
epilepsy, Alzheimer’s Disease and other forms of dementia,
transient ischaemic attack, migraine and tumours of the brain.
(2) Technetium (99mTc) Exametazime Injection is also indicated for
in vitro technetium-99m leucocyte labelling, the labelled leucocytes
subsequently being re-injected and scintigraphy carried out to
image the sites of localisation. This procedure may be used in the
detection of sites of focal infection (e.g. abdominal abscess), in the
investigation of pyrexia of unknown origin and in the evaluation of
inflammatory conditions not associated with infection such as
inflammatory bowel disease.
4.2 Posology and method of administration
The route of administration is direct intravenous injection for brain
scintigraphy studies and intravenous injection of labelled leucocytes
post labelling in vitro.
Posology
Adults and the elderly population
1) for brain scintigraphy, 350-500 MBq
2) for in vivo localisation of technetium-99m-labelled leucocytes,
200 MBq
Normally a once-only diagnostic procedure.
Paediatric population
Technetium-99m exametazime and technetium-99m-labelled leucocytes
are not recommended for administration to children.
Method of administration
This medicinal product should be reconstituted before administration to
the patient.
For instructions on reconstitution of the medicinal product before
administration, see section 12.
For patient preparation, see section 4.4
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed
in section 6.1.
4.4 Special warnings and precautions for use
Potential for hypersensitivity or anaphylactic reactions
The possibility of hypersensitivity including anaphylactic/anaphylactoid
reactions should always be considered. If hypersensitivity or anaphylactic
reactions occur, the administration of the medicinal product must
be discontinued immediately and intravenous treatment initiated, if
necessary. To enable immediate action in emergencies, the necessary
medicinal products and equipment such as endotracheal tube and
ventilator must be immediately available.
Re-injected Ceretec labelled leukocytes only
When preparing technetium-99m-labelled leucocytes it is essential that
cells are washed free of sedimentation agents before they are
re-injected into the patient as materials used in cell separation may
cause hypersensitivity reactions.
Individual benefit/risk justification
For each patient, the radiation exposure must be justifiable by the likely
benefit. The activity administered should in every case be as low as
reasonably achievable to obtain the required diagnostic information.
Renal impairment and hepatic impairment
Careful consideration of the benefit risk ratio in these patients is required
since an increased radiation exposure is possible.
Paediatric population
Paediatric population, see section 4.2
Patient preparation
The patient should be well hydrated before the start of the examination
and urged to void as often as possible during the first hours after the
examination in order to reduce radiation.
Specific warnings
Depending on the time when you administer the injection the content of
sodium given to the patient may in some cases be greater than 1 mmol.
This should be taken into account in patients on low sodium diet.
Precautions with respect to environmental hazard see section 6.6.

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4.5 Interaction with other medicinal products and other forms
of interaction
No interaction studies have been performed.
4.6 Fertility, pregnancy and lactation
Women with childbearing potential
When an administration of radiopharmaceuticals to a woman of
childbearing potential is intended, it is important to determine whether
or not she is pregnant. Any woman who has missed a period should be
assumed to be pregnant until proven otherwise. If in doubt about her
potential pregnancy (if the woman has missed a period, if the period is
very irregular, etc.), alternative techniques not using ionising radiation (if
there are any) should be offered to the patient.
Pregnancy
No data are available on the use of this product in human pregnancy.
Animal reproduction studies have not been performed.
Radionuclide procedures carried out on pregnant women also involve
radiation doses to the foetus. Only essential investigations should
therefore be carried out during pregnancy, when the likely benefit far
exceeds the risk incurred by the mother and the foetus.
Breast-feeding:
Before administering a radioactive medicinal product to a mother who is
breast-feeding consideration should be given as to whether the

investigation could be reasonably delayed until after the mother has
ceased breast-feeding and as to whether the most appropriate choice of
radiopharmaceutical has been made, bearing in mind the secretion of
activity in breast milk.
If the administration is considered necessary, breast-feeding should be
interrupted for 12 hours and the expressed feeds discarded.
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have
been performed.
4.8 Undesirable effects
The frequencies of undesirable effects are defined as follows:
Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000
to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not
known (cannot be estimated from the available data)
Immune system disorders
Not known: Hypersensitivity including rash, erythema, urticaria,
angiooedema, pruritus.
Re-injected Ceretec labelled leuokocytes only:
Not Know: Hypersensitivity including rash, erythema, urticaria,
angiooedema, pruritus, anaphylactoid reaction or anaphylactoid shock
Nervous system disorders
Not known: Headache, dizziness, paraesthesia
Vascular disorders
Not known: Flushing
Gastrointestinal disorders
Not known: Nausea, vomiting
General disorders and administration site conditions
Not known: Asthenic conditions (e.g., malaise, fatigue)
Exposure to ionising radiation is linked with cancer induction and a
potential for development of hereditary defects. As the effective dose is
5.2 mSv when the maximal recommended activity of 555 MBq is
administered these adverse events are expected to occur with a low
probability.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the
medicinal product is important. It allows continued monitoring of the
benefit/risk balance of the medicinal product. Healthcare professionals
are asked to report any suspected adverse reactions via the Yellow Card
Scheme at www.mhra.gov.uk/yellowcard
4.9 Overdose
In the event of the administration of a radiation overdose frequent
micturition and defecation should be encouraged in order to minimise
the absorbed dose to patient.
5.

PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: diagnostic radiopharmaceuticals, central
nervous system, ATC code: V09AA01
Pharmacotherapeutic group: diagnostic radiopharmaceuticals,
inflammation and infection detection, ATC code: V09HA02
At the chemical concentrations and activities used for diagnostic
procedures technetium-99m exametazime and technetium-99mlabelled leucocytes do not appear to exert any pharmacodynamic
effects.
5.2 Pharmacokinetic properties
(1) Direct intravenous injection
The technetium-99m complex of the active ingredient is uncharged,
lipophilic and of sufficiently low molecular weight to cross the bloodbrain barrier. It is rapidly cleared from the blood after intravenous
injection. Uptake in the brain reaches a maximum of 3.5-7.0% of the
injected dose within one minute of injection. Up to 15% of the cerebral
activity washes out of the brain 2 minutes post injection after which
there is little loss of activity for the following 24 hours except by physical
decay of technetium-99m. The activity not associated with the brain is
widely distributed throughout the body particularly in muscle and
soft tissue. About 20% of the injected dose is removed by the liver
immediately after injection and excreted through the hepatobiliary
system. About 40% of the injected dose is excreted through the kidneys
and urine over the 48 hours after injection resulting in a reduction in
general muscle and soft tissue background.
(2) Injection of labelled leucocytes
Technetium-99m-labelled leucocytes distribute between the
marginating pools of the liver (within 5 minutes) and spleen (within about
40 minutes), and the circulating pool, (the latter represents
approximately 50% of the leucocyte pool). Approximately 37% of the
cell associated technetium-99m is recoverable from the circulating pool
40 minutes after injection. Technetium-99m activity is slowly eluted from
the cells and is excreted partly by the kidneys and partly via the liver into
the gall bladder. This results in increasing amounts of activity being seen
in the intestines.
5.3 Preclinical safety data
There is no additional preclinical safety data of relevance for the
prescriber in recognising the safety profile of the product used for the
authorised indications.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium chloride
Stannous chloride dihydrate
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products
except those mentioned in section 12.
6.3 Shelf life
26 weeks from the day of manufacture.
Store the reconstituted product below 25°C. Do not freeze or refrigerate.
The labelled product must be injected within 30 minutes of
reconstitution.
6.4 Special precautions for storage
For storage conditions after reconstitution of the medicinal product,
see section 6.3.
Storage should be in accordance with national regulations for radioactive
materials.
6.5 Nature and contents of container
10ml Type I Ph.Eur., clear, colourless, borosilicate glass vial sealed with a
chlorobutyl rubber closure and oversealed with an aluminium overseal
with a blue flip off cap.
Pack sizes: kit contains 2 or 5 vials.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
General warning
Radiopharmaceuticals should be received, used and administered
only by authorised persons in designated clinical settings. Its receipt,
storage, use, transfer and disposal are subject to the regulations and/or
appropriate licences of the competent official organisation.
Radiopharmaceuticals should be prepared in a manner which satisfies
both radiation safety and pharmaceutical quality requirements.
Appropriate aseptic precautions should be taken.

Contents of the vial are intended only for use in the preparation of
technetium (99mTc) exametazime injection and are not to be administered
directly to the patient without first undergoing the preparative procedure.
For instructions on reconstitution of the medicinal product before
administration, see section 12.
If at any time in the preparation of this product the integrity of this
vial is compromised it should not be used. Administration procedures
should be carried out in a way to minimise risk of contamination of the
medicinal product and irradiation of the operators. Adequate shielding
is mandatory.
The content of the kit before reconstitution is not radioactive. However,
after sodium pertechnetate (99mTc), Ph. Eur. is added, adequate shielding
of the final preparation must be maintained.
The administration of radiopharmaceuticals creates risks for other
persons from external radiation or contamination from spill of urine,
vomiting etc. Radiation protection precautions in accordance with
national regulations must therefore be taken.
After use, all materials associated with the preparation and administration
of radiopharmaceuticals, including any unused product and its container,
should be decontaminated or treated as radioactive waste and disposed
of in accordance with local requirements.
7. MARKETING AUTHORISATION HOLDER
GE Healthcare Limited
Amersham Place
Little Chalfont
Buckinghamshire HP7 9NA
United Kingdom
8. MARKETING AUTHORISATION NUMBER
UK:
PL 00221/0126
9.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

UK

Date of first authorisation
09 October 1995

Date of last renewal
21 March 2006

10. DATE OF REVISION OF THE TEXT
August 2016
11 DOSIMETRY
Technetium (99mTc) is produced by means of a (99Mo/99mTc) generator and
decays with the emission of gamma radiation with a mean energy of
140 keV and a half-life of 6.02 hours to technetium (99Tc) which, in view
of its long half-life of 2.13 x 105 years can be regarded as quasi stable.
(1) Brain scinitigraphy
The table below shows the dosimetry as calculated according to the
Publication 62 of the ICRP (International Commission on Radiological
Protection in Biomedical Research, Pergamon Press 1991) following
administration of 99mTc-exametazime to adults.

Absorbed dose per unit activity administered
(mGy/MBq) Adult

Organ

Adrenals
Bladder
Bone surfaces
Brain
Breast
Gall bladder
GI tract
Stomach
SI
ULI
LLI

5.3E-03
2.3E-02
5.1E-03
6.8E-03
2.0E-03
1.8E-02

Heart
Kidneys
Liver
Lungs
Muscles
Oesophagus
Ovaries
Pancreas

3.7E-03
3.4E-02
8.6E-03
1.1E-02
2.8E-03
2.6E-03
6.6E-03
5.1E-03

Red marrow
Skin
Spleen
Testes
Thymus
Thyroid
Uterus

3.4E-03
1.6E-03
4.3E-03
2.4E-03
2.6E-03
2.6E-02
6.6E-03

Remaining organs

3.2E-03

6.4E-03
1.2E-02
1.8E-02
1.5E-02

Effective dose
(mSv/MBq)

9.3E-03

Effective Dose is 4.7 mSv/500 MBq (70 kg individual).
(2) In vivo localisation of technetium-99m-labelled leucocytes
The table below shows the dosimetry as calculated according to the
Publication 80 of the ICRP (International Commission on Radiological
Protection, Radiation Dose to Patients from Radiopharmaceuticals,
Pergamon Press 1998).
Organ

Adrenals
Bladder
Bone surfaces
Brain
Breast
Gall bladder
GI-tract
Stomach
SI
Colon
ULI
LLI
Heart
Kidneys
Liver
Lungs
Muscles
Oesophagus
Ovaries
Pancreas
Red marrow
Skin
Spleen
Testes
Thymus
Thyroid
Uterus
Remaining organs
Effective dose
(mSv/MBq)

Absorbed dose per unit activity
administered (mGy/MBq)
Adult 15 years 10 years 5 years 1 year
1.0E-02 1.2E-02 1.8E-02 2.6E-02 4.3E-02
2.6E-03 3.5E-03 5.2E-03 7.8E-03 1.4E-02
1.6E-02 2.1E-02 3.4E-02 6.1E-02 1.5E-01
2.3E-03 2.9E-03 4.4E-03 7.0E-03 1.3E-02
2.4E-03 2.9E-03 4.9E-03 7.6E-03 1.3E-02
8.4E-03 1.0E-02 1.6E-02 2.5E-02 3.6E-02
8.1E-03
4.6E-03
4.3E-03
4.7E-03
3.7E-03
9.4E-03
1.2E-02
2.0E-02
7.8E-03
3.3E-03
3.5E-03
3.9E-03
1.3E-02
2.3E-02
1.8E-03
1.5E-01
1.6E-03
3.5E-03
2.9E-03
3.4E-03
3.4E-03
1.1E-02

9.6E-03
5.7E-03
5.4E-03
5.9E-03
4.8E-03
1.2E-02
1.4E-02
2.6E-02
9.9E-03
4.1E-03
4.2E-03
5.0E-03
1.6E-02
2.5E-02
2.1E-03
2.1E-01
2.1E-03
4.2E-03
3.7E-03
4.3E-03
4.2E-03
1.4E-02

1.4E-02
8.7E-03
8.4E-03
9.3E-03
7.3E-03
1.7E-02
2.2E-02
3.8E-02
1.5E-02
6.0E-03
5.8E-03
7.2E-03
2.3E-02
4.0E-02
3.4E-03
3.1E-01
3.2E-03
5.8E-03
5.8E-03
6.5E-03
6.3E-03
2.2E-02

2.0E-02
1.3E-02
1.2E-02
1.4E-02
1.0E-02
2.5E-02
3.2E-02
5.4E-02
2.3E-02
8.9E-03
8.6E-03
1.1E-02
3.4E-02
7.1E-02
5.5E-03
4.8E-01
5.1E-03
8.6E-03
9.3E-03
9.7E-03
9.5E-03
3.4E-02

Effective Dose is 2.2 mSv/200 MBq (70 kg individual).

3.2E-02
2.1E-02
2.1E-02
2.3E-02)
1.8E-02)
4.4E-02
5.4E-02
9.7E-02
4.1E-02
1.6E-02
1.5E-02
1.8E-02
5.3E-02
1.4E-01
1.0E-02
8.5E-01
9.2E-03
1.5E-02
1.7E-02
1.6E-02
1.6E-02
6.2E-02

12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS
Withdrawals should be performed under aseptic conditions. The vials
must not be opened before disinfecting the stopper, the solution should
be withdrawn via the stopper using a single dose syringe fitted with
suitable protective shielding and a disposable sterile needle or using an
authorised automated application system. If the integrity of this vial is
compromised, the product should not be used.
Method of preparation of technetium-99m exametazime for
intravenous injection or in vitro leucocyte labelling
Use aseptic technique throughout.
(1) Place the vial in a shielding container and swab the closure with the
sanitising swab provided.
(2) Using a 10ml syringe, inject into the shielded vial 5ml of sterile
eluate from a technetium-99m generator (see notes 1 - 6). Before
withdrawing the syringe from the vial withdraw 5ml of gas from the
space above the solution to normalise the pressure in the vial. Shake
the shielded vial for 10 seconds to ensure complete dissolution of the
powder.
(3) Assay the total activity and calculate the volume to be injected or
used for in vitro technetium-99m-leucocyte labelling.
(4) Complete the label provided and attach to the vial.
(5) Use within a maximum of 30 minutes after reconstitution. Discard
any unused material.
Note:
(1) For the highest radiochemical purity reconstitute with freshly eluted
technetium-99m generator eluate.
(2) Use only eluate which was eluted less than 2 hours previously from
a generator which was eluted within 24 hours.
(3) 0.37-1.11 GBq (10-30 mCi) technetium-99m may be added to the
vial.
(4) Before reconstitution the generator eluate may be adjusted to the
correct radioactive concentration (0.37-1.11 GBq in 5 ml) by dilution
with sodium chloride for injection.
(5) Pertechnetate complying with the specifications prescribed by the
USP and BP/Ph.Eur. Monographs on Sodium Pertechnetate (99mTc)
Injection should be used.
(6) The pH of the prepared injection/labelling agent is in the range
9.0-9.8.
Procedure for separation of leucocytes and subsequent in vitro labelling
with technetium-99m exametazime
Use aseptic technique throughout.
(1) Draw 9 ml of acid-citrate-dextrose (ACD) (see note a) into each of
two 60 ml plastic non-heparinized syringes.
(2) Withdraw 51ml of patient’s blood into each syringe, using a 19G
Butterfly needle infusion set. Close the syringes with sterile hubs.
(3) Dispense 2ml sedimentation agent (see note b) into each of
5 Universal containers or tubes.
(4) Without attaching a needle to the syringes dispense 20 ml of blood
into each of the 5 Universal tubes containing sedimentation agent.
Dispense the remaining 20ml of blood into a tube without
sedimentation agent.
TIP: To avoid bubbles and frothing run the blood gently down the sides
of the tubes.
(5) Mix the blood and sedimentation agent with one gentle inversion.
Remove the cap of the Universal tube and burst the bubble formed
at the top using a sterile needle. Replace the cap and allow the
tubes to stand for 30-60 minutes for erythrocyte sedimentation to
take place.
TIP: The period of time for erythrocyte sedimentation depends on the
patient’s condition. As a guideline it should be stopped when the blood
has sedimented to give approximately half the volume as sedimented
red cells.
(6) Meanwhile centrifuge the tube containing 20 ml of blood and no
sedimentation agent at 2000g for 10 minutes. This will yield
supernatant cell-free plasma (CFP) containing ACD which is retained,
at room temperature, for use as a cell labelling and re-injection
medium.
(7) When sufficient red cell sedimentation has taken place [see (5)]
carefully transfer 15 ml aliquots of the cloudy straw-coloured
supernatant into clean Universal tubes. Take care to avoid
withdrawing any sedimented erythrocytes. The supernatant is
leucocyte-rich, platelet-rich plasma [LRPRP].
TIP: Do not use needles on sampling syringes to avoid unnecessary cell
damage.
(8) Centrifuge the LRPRP at 150g for 5 minutes to give supernatant,
platelet-rich plasma (PRP) and a pellet of “mixed” leucocytes.
(9) Remove as much of the PRP as possible into clean Universal
tubes and further centrifuge at 2000g for 10 minutes to give more
supernatant, CFP containing sedimentation agent. This will be used
to wash the cells after labelling.
(10) Meanwhile loosen the pellets of “mixed” leucocytes by very gently
tapping and swirling the Universal tubes. Using a syringe, without an
attached needle, pool all the cells into one tube then, using the same
syringe, add 1ml of cell-free plasma containing ACD (from 6) and
gently swirl to resuspend.
(11) Reconstitute a vial of Ceretec with 5 ml of technetium-99m
generator eluate containing approximately 500 MBq (13.5 mCi)
of 99mTcO4- (using the procedure described above).
(12) Immediately following reconstitution add 4 ml of the resulting
technetium-99m exametazime solution to the “mixed” leucocytes in
CFP (from 10).
(13) Gently swirl to mix and incubate for 10 minutes at room temperature.
(14) If required, immediately spot the chromatography strips for
assessment of radiochemical purity of the technetium-99m
exametazime, as instructed overleaf.
(15) On completion of incubation carefully add 10ml of CFP containing
sedimentation agent (from 9) to the cells, in order to stop labelling.
Gently invert the cells to mix.
(16) Centrifuge at 150g for 5 minutes.
(17) Remove and retain all of the supernatant.
TIP: It is critical that all the supernatant which contains unbound
technetium-99m exametazime is removed at this stage. This can be best
achieved using a syringe with a wide-bore [19G] needle.
(18) Gently resuspend the technetium-99m labelled mixed leucocyte
preparation in 5-10 ml of CFP containing ACD from (6). Gently swirl
to mix.
(19) Measure the radioactivity in the cells and in the supernatant from
(17). Calculate the labelling efficiency [LE] which is defined as the
activity in the cells as a percentage of the sum of the activity in the
cells and the activity in the supernatant.
TIP Labelling efficiency depends on the patient’s leucocyte count and
will vary according to the volume of the initial blood sample. Using the
volumes in (2), a LE of about 55% might be expected.
(20) Without attaching a needle, carefully draw up the labelled cells into
a plastic, non-heparinised syringe and close it with a sterile hub.
Measure the radioactivity.
(21) Labelled cells are now ready for re-injection. This should be
performed without delay.

Note:
(a) Acid-citrate-dextrose (ACD) should be made up as follows:
NIH Formula A. For 1 litre add 22g trisodium citrate, 8g citric acid,
22.4g dextrose and make up to 1 litre with Water for injections.
The product should be manufactured under aseptic condition.
Commercial preparations of the product are also available.
The product should be stored under the conditions recommended
by the manufacturer and should be used only up to the expiry date
given by the manufacturer.
(b) 6% hydroxyethyl starch should be manufactured under aseptic
conditions. Commercial preparations of the product are available.
The product should be stored under the conditions recommended
by the manufacturer and should be used only up to the expiry date
given by the manufacturer.
Quality control
Three potential radiochemical impurities may be present in the prepared
exametazime injection. These are a secondary 99mTc exametazime
complex, free pertechnetate and reduced-hydrolysed-technetium-99m.
A combination of two chromatographic systems is necessary for the
determination of the radiochemical purity of the injection.
Test samples are applied by needle approximately 2.5cm from the
bottom of two Glass Microfiber Chromatography Paper impregnated
with Silicic Acid (GMCP-SA) strips (2 cm (± 2 mm )x 20cm). The strips
are then immediately placed in prepared ascending chromatography
development tanks, one containing butan-2-one and the other 0.9% aq.
sodium chloride (1cm depth fresh solvent). After a 14cm elution the strips
are removed, solvent fronts marked, the strips dried and the distribution
of activity determined using suitable equipment.
Interpretation of chromatograms
System 1 (GMCP-SA:butan-2-one (methyl ethyl ketone))
Secondary 99mTc exametazime complex and reduced-hydrolysedtechnetium remain at the origin.
Lipophilic 99mTc exametazime complex and pertechnetate migrate at
Rf 0.8-1.0.
System 2 (GMCP-SA: 0.9% sodium chloride)
Lipophilic 99mTc exametazime complex, secondary 99mTc exametazime
complex and reduced-hydrolysed-Tc remain at the origin.
Pertechnetate migrates at Rf 0.8-1.0.
(1) Calculate the percentage of activity due to both secondary 99mTc
exametazime complex and reduced-hydrolysed-technetium-99m
from System 1 (A%). Calculate the percentage of activity due to
pertechnetate from System 2 (B%).
(2) The radiochemical purity (as percentage lipophilic 99mTc exametazime
complex) is given by:
100-(A%+B%) where:
A% represents the level of secondary 99mTc exametazime complex plus
reduced-hydrolysed technetium-99m
B% represents the level of pertechnetate.
A radiochemical purity of at least 80% may be expected provided the
test samples have been taken and analysed within 30 minutes of
reconstitution.

Document: 1189057 GBR Version: 0

13 OTHER INFORMATION
Manufacturer
GE Healthcare AS
Nycoveien 1-2
0401 OSLO
Norway
Ceretec is a trademark of GE Healthcare.
GE and the GE Monogram are trademarks of General Electric Company.

GE Healthcare

HEALTHCARE PROFESSIONAL
INFORMATION

Ceretec™
500 micrograms kit for
radiopharmaceutical
preparation.
Exametazime

1189057

1189057 GBR

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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