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FLUDEOXYGLUCOSE (18F)-IBA SOLUTION FOR INJECTION

Active substance(s): FLUDEOXYGLUCOSE (18-F)

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Fludeoxyglucose (18F)-IBA 185 MBq/mL solution for injection

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

1 mL contains 185 MBq of fludeoxyglucose (18F) at the date and time of calibration.
The activity per vial ranges from 90 MBq to 1850 MBq at the date and time of
calibration.
Fluorine (18F) decays to stable oxygen (18O) with a half-life of 110 minutes by
emitting a positronic radiation of maximum energy of 634 keV, followed by photonic
annihilation radiations of 511 keV.
Excipient with known effects:
Each mL of fludeoxyglucose (18F) contains 9 mg of sodium chloride.
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM

Solution for injection
Clear, colourless or slightly yellow solution.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

This medicinal product is for diagnostic use only.
Fludeoxyglucose (18F) is indicated for use with positron emission tomography (PET)
in adults and paediatric population.
Oncology
In patients undergoing oncologic diagnostic procedures describing function or
diseases where enhanced glucose influx of specific organs or tissues is the diagnostic
target. The following indications are sufficiently documented (see also section 4.4):
Diagnosis:
• Characterisation of solitary pulmonary nodules
• Detection of cancer of unknown origin, revealed for example by cervical
adenopathy, liver or bones metastases.



Characterisation of a pancreatic mass

Staging:
• Head and neck cancers including assistance in guiding biopsy
• Primary lung cancer
• Locally advanced breast cancer
• Oesophageal cancer
• Carcinoma of the pancreas
• Colorectal cancer particularly in restaging recurrences
• Malignant lymphoma
• Malignant melanoma, Breslow > 1.5 mm or lymph node metastasis at first
diagnosis
Monitoring of therapeutic response:
• Malignant lymphoma
• Head and neck cancers
Detection in case of reasonable suspicion of recurrences:
• Glioma with high grade malignancy (III or IV)
• Head and neck cancers
• Thyroid cancer (non-medullary): patients with increased thyroglobulin serum
levels and negative radioactive iodine whole body scintigraphy
• Primary lung cancer
• Breast cancer
• Carcinoma of the pancreas
• Colorectal cancer
• Ovarian cancer
• Malignant lymphoma
• Malignant melanoma
Cardiology
In the cardiologic indication, the diagnostic target is viable myocardial tissue that
takes-up glucose but is hypo-perfused, as it must be assessed beforehand using
appropriate blood-flow imaging techniques.
• Evaluation of myocardial viability in patients with severe impaired left
ventricular function who are candidates for revascularisation when
conventional imaging modalities are not contributive.
Neurology
In the neurologic indication the interictal glucose hypometabolism is the diagnostic
target.
• Localisation of epileptogenic foci in the presurgical evaluation of partial
temporal epilepsy.
Infectious or inflammatory diseases
In infectious or inflammatory diseases, the diagnostic target is tissue or structures with
an abnormal content of activated white blood cells.
In infectious or inflammatory diseases, the following indications are sufficiently
documented:

Localisation of abnormal foci guiding the aetiologic diagnosis in case of fever of
unknown origin.
Diagnosis of infection in case of:
• Suspected chronic infection of bone and/or adjacent structures: osteomyelitis,
spondilitis, diskitis or osteitis including when metallic implants are present
• Diabetic patient with a foot suspicious of Charcot’s neuroarthropathy,
osteomyelitis and/or soft tissue infection
• Painful hip prosthesis
• Vascular prosthesis
• Fever in an AIDS patient
• Detection of septic metastatic foci in case of bacteraemia or endocarditis (see
also section 4.4).
Detection of the extension of inflammation in case of:
• Sarcoidosis
• Inflammatory bowel disease
• Vasculitis involving the great vessels
Therapy follow-up:
Unresectable alveolar echinococcosis, in search for active localisations of the parasite
during medical treatment and after treatment discontinuation.
4.2

Posology and method of administration

Posology
Adults and elderly population
The recommended activity for an adult weighing 70 kg is 100 to 400 MBq (this
activity has to be adapted according to the body weight of the patient, the type of
camera used and acquisition mode), administered by direct intravenous injection.
Renal and hepatic impairment
Careful consideration of the activity to be administered is required since an increased
radiation exposure is possible in these patients.
Extensive dose-range and adjustment studies with this medicinal product in normal
and special populations have not been performed.
The pharmacokinetics of fludeoxyglucose (18F) in renally impaired patients has not
been characterised.
Paediatric population
The use in children and adolescents has to be considered carefully, based upon
clinical needs and assessing the risk/benefit ratio in this patient group. The activities
to be administered to children and adolescents may be calculated according to the
recommendations of the European Association of Nuclear Medicine (EANM)
paediatric dosage card; the activity administered to children and to adolescents may
be calculated by multiplying a baseline activity (for calculation purposes) by the
weight-dependent multiples given in the table below.

A[MBq]Administered = Baseline Activity × Multiple
The baseline activity for 2D imaging is 25.9 MBq and for 3D imaging 14.0 MBq
(recommended in children).
Weight
[kg]
3
4
6
8
10
12
14
16
18
20

Multiple
1
1.14
1.71
2.14
2.71
3.14
3.57
4.00
4.43
4.86

Weight
[kg]
22
24
26
28
30
32
34
36
38
40

Multiple
5.29
5.71
6.14
6.43
6.86
7.29
7.72
8.00
8.43
8.86

Weight
[kg]
42
44
46
48
50
52-54
56-58
60-62
64-66
68

Multiple
9.14
9.57
10.00
10.29
10.71
11.29
12.00
12.71
13.43
14.00

Method of administration
For intravenous use.
For multidose use.
The activity of fludeoxyglucose (18F) has to be measured with activimeter
immediately prior to injection.
The injection of fludeoxyglucose (18F) must be intravenous in order to avoid
irradiation as a result of local extravasation, as well as imaging artefacts.
For intructions on dilution of the medical product before administration, see section
12.
For patient preparation, see section 4.4.
Image acquisition
The emission scans are usually started 45 to 60 minutes after the injection of
fludeoxyglucose (18F). Provided a sufficient activity remains for adequate counting
statistics, fludeoxyglucose (18F)-PET can also be performed up to two or three hours
after administration, thus reducing background activity.
If required, repeated fludeoxyglucose (18F) PET examinations can be reiterated within
a short period of time.
4.3

Contraindications


4.4

Hypersensitivity to the active substance -and to any of the excipients listed in
section 6.1.
Special warnings and precautions for use

Potential for hypersensitivity or anaphylactic reactions

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 products and
equipment such as endotracheal tube and ventilator must be immediately available.
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 and hepatic impairment
Due to the major renal excretion of fludeoxyglucose (18F), in patients with reduced
kidney function, careful consideration of the benefit risk ratio in these patients is
required since an increased radiation exposure is. Activity should be adjusted if
necessary.
Paediatric population
For information on the use in paediatric population, see sections 4.2 or 5.1.
Careful consideration of the indication is required since the effective dose per MBq is
higher than in adults (see section 11.).
Patient preparation
Fludeoxyglucose (18F)-IBA should be given to sufficiently hydrated patients fasting
for a minimum of 4 hours, in order to obtain a maximum target activity, since glucose
uptake in the cells is limited (“saturation kinetics”). The amount of liquid should not
be limited (beverages containing glucose must be avoided).
In order to obtain images of best quality and to reduce the radiation exposure of the
bladder, patients should be encouraged to drink sufficient amounts and to empty their
bladder prior to and after the PET examination.
- Oncology and neurology and infectious diseases
In order to avoid hyperfixation of the tracer in muscle, it is advisable for patients to
avoid all strenuous physical activity prior to the examination and to remain at rest
between the injection and examination and during acquisition of images (patients
should be comfortably lying down without reading or speaking).
The cerebral glucose metabolism depends on the brain activity. Thus, neurological
examinations should be performed after a relaxation period in a darkened room and
with low background noise.
A blood glucose test should be performed prior to administration since
hyperglycaemia may result in a reduced sensitivity of Fludeoxyglucose (18F)-IBA,
especially when glycaemia is greater than 8 mmol/L. Similarly, PET with
fludeoxyglucose (18F) should be avoided in subjects presenting uncontrolled diabetes.
- Cardiology
Since glucose uptake in the myocardium is insulin-dependent, for a myocardial
examination a glucose loading of 50 g approximately 1 hour prior to the
administration of Fludeoxyglucose (18F)-IBA is recommended. Alternatively,
especially for patients with diabetes mellitus, the blood sugar level can be adjusted by
a combined infusion of insulin and glucose (Insulin-Glucose-Clamp) if needed.
Interpretation of the PET with fludeoxyglucose (18F) images

In the exploration of inflammatory bowel diseases, diagnostic performance of
fludeoxyglucose (18F) has not been directly compared with that of scintigraphy using
labelled white blood cells which may be indicated prior to fludeoxyglucose (18F) PET
or after fludeoxyglucose (18F) PET when inconclusive.
Infectious and/or inflammatory diseases as well as regenerative processes after
surgery can result in a significant uptake of fludeoxyglucose (18F) and therefore lead
to false positive results, when search for infectious or inflammatory lesions is not the
aim of the fludeoxyglucose (18F) PET.
In cases where fludeoxyglucose (18F) accumulation can be caused by either cancer,
infection or inflammation, additional diagnostic techniques for the determination of
the causative pathologic alteration may be required to supplement the information
obtained by PET with fludeoxyglucose (18F). In some settings e.g. staging of
myeloma, both malignant and infectious foci are searched for and may be
distinguished with a good accuracy on topographic criteria e.g. uptake at
extramedullary sites and/or bone and joint lesions would be atypical for multiple
myeloma lesions and identified cases associated with infection. There are currently no
other criteria to distinguish infection and inflammation by means of fludeoxyglucose
(18F) imaging.
Because of the high physiologic uptake of fludeoxyglucose (18F) within brain, heart
and kidneys, PET/CT with fludeoxyglucose (18F) has not been evaluated for the
detection of septic metastatic foci in these organs when the patient has been referred
due to bacteraemia or endocarditis.
False positive or false negative PET with fludeoxyglucose (18F) results cannot be
excluded after radiotherapy within the first 2-4 months. If the clinical indication is
demanding an earlier diagnosis by PET with fludeoxyglucose (18F), the reason for
earlier PET with fludeoxyglucose (18F) examination must be reasonably documented.
A delay of at least 4-6 weeks after the last administration of chemotherapy is optimal,
in particular to avoid false negative results. If the clinical indication is demanding an
earlier diagnosis by PET with fludeoxyglucose (18F), the reason for earlier PET with
fludeoxyglucose (18F) examination must be reasonably documented. In case of
chemotherapy regimen with cycles shorter than 4 weeks, the PET with
fludeoxyglucose (18F) examination should be done just before re-starting a new cycle.
In low-grade lymphoma, lower oesophagus cancer and suspicion of recurrent ovarian
cancer, only positive predictive values have to be considered because of a limited
sensitivity of PET with fludeoxyglucose (18F).
Fludeoxyglucose (18F) is not effective in detecting brain metastases.
The accuracy of fludeoxyglucose (18F) PET imaging is better using PET/CT than PET
cameras alone.
When a hybrid PET-CT scanner is used with or without administration CT contrast
media, some artefacts may occur on the attenuation-corrected PET images.
After the procedure
Close contact with infants and pregnant women should be restricted during the initial
12 hours following the injection.
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 (23 mg).

This should be taken into account in patient on low sodium diet.
Precautions with respect to environmental hazard see section 6.6.
4.5

Interaction with other medicinal products and other forms of interaction

All medicinal products that modify blood glucose levels can affect the sensitivity of
the examination (e.g. corticosteroids, valproate, carbamazepine, phenytoin,
phenobarbital and catecholamines).
Under administration of colony-stimulating factors (CSFs), there is an increased
uptake of fludeoxyglucose (18F) in the bone marrow and the spleen for several days.
This must be taken into account for the interpretation of PET imaging. Separating
CSF therapy from PET imaging by an interval of at least 5 days may diminish this
interference.
The administration of glucose and insulin influences the influx of fludeoxyglucose
(18F) into the cells. In the case of high blood glucose levels as well as low plasma
insulin levels, the influx of fludeoxyglucose (18F) into organs and tumours is reduced.
No formal studies on the interaction between fludeoxyglucose (18F) and any contrast
for computed tomography have been performed.
4.6

Fertility, pregnancy and lactation

Women of 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
Radionuclide procedures carried out on pregnant women also involve radiation dose
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 foetus.
Breastfeeding
Before administering radiopharmaceuticals to a mother who is breastfeeding,
consideration should be given to the possibility of delaying the administration of
radionuclide until the mother has ceased breastfeeding, and to what is the most
appropriate choice of radiopharmaceuticals, bearing in mind the secretion of activity
in breast milk. If the administration is considered necessary, breastfeeding should be
interrupted for 12 hours and the expressed feeds discarded.
Close contact with infants should be restricted during the initial 12 hours following
injection.
Fertility
No studies on fertility have been performed.

4.7

Effects on ability to drive and use machines

Not relevant.
4.8

Undesirable effects

Exposure to ionising radiation is linked with cancer induction and a potential for
development of hereditary defects. As the effective dose is 7.6 mSv when the
maximal recommended activity of 400 MBq is administered these adverse reactions
are expected to occur with a low probability.
4.9

Overdose

In the event of administration of a radiation overdose with fludeoxyglucose (18F) the
absorbed dose to the patient should be reduced where possible by increasing the
elimination of the radionuclide from the body by forced diuresis and frequent bladder
voiding. It might be helpful to estimate the effective dose that was applied.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: diagnostic radiopharmaceutical, other diagnostic
radiopharmaceuticals for tumour detection,ATC code: V09IX 04
Pharmacodynamic effects
At the chemical concentrations used for diagnostic examinations, fludeoxyglucose
(18F) does not appear to have any pharmacodynamic activity.
5.2

Pharmacokinetic properties

Distribution
Fludeoxyglucose (18F) is a glucose analogue, which is accumulated in all cells using
glucose as primary energy source. Fludeoxyglucose (18F) is accumulated in tumours
with a high glucose turnover.
Following intravenous injection, the pharmacokinetic profile of fludeoxyglucose (18F)
in the vascular compartment is biexponential. It has a distribution time of 1 minute
and an elimination time of approximately 12 minutes.
In healthy subjects, fludeoxyglucose (18F) is widely distributed throughout the body,
particularly in the brain and heart, and to a lesser degree in the lungs and liver.
Organ uptake
The cellular uptake of fludeoxyglucose (18F) is performed by tissue-specific carrier
systems, which are partly insulin-dependent and, thus, can be influenced by eating,
nutritional condition and the existence of a diabetes mellitus. In patients with a

diabetes mellitus a reduced uptake of fludeoxyglucose (18F) into the cells occurs due
to a changed tissue distribution and glucose metabolism.
Fludeoxyglucose (18F) is transported via the cell membrane in similar fashion to
glucose, but only undergoes the first step of glycolysis resulting in formation of
fludeoxyglucose (18F)-6-phosphate, which remains trapped within the tumour cells
and is not further metabolised. Since the following dephosphorylation by intracellular
phosphatases is slow, fludeoxyglucose (18F)-6-phosphate is retained in the tissue over
several hours (trapping-mechanism).
Fludeoxyglucose (18F) passes the blood-brain barrier. Approximately 7 % of the
injected dose are accumulated in the brain within 80-100 minutes after injection.
Epileptogenic foci exhibit a reduced glucose metabolism in the seizure free phases.
Approximately 3 % of the injected activity are taken-up by the myocardium within 40
minutes. The distribution of fludeoxyglucose (18F) in normal heart is mainly
homogenous, however, regional differences of up to 15 % are described for the
interventricular septum. During and after a reversible myocardial ischemia, an
increased glucose uptake occurs into the myocardial cell.
0.3 % and 0.9 - 2.4 % of the injected activity are accumulated in pancreas and lung.
Fludeoxyglucose (18F) is also bound to a lesser extent to ocular muscle, pharynx and
intestine. Binding to muscle may be seen following recent exertion and in the event of
muscular effort during the examination.
Elimination
Elimination of fludeoxyglucose (18F) is chiefly renal, with 20 % of activity being
excreted in urine in the 2 hours following injection.
Binding to renal parenchyma is weak, but because of renal elimination of
fludeoxyglucose (18F), the entire urinary system, particularly the bladder, exhibits
marked activity.
5.3

Preclinical safety data

Toxicological studies with mice and rats have demonstrated that with a single
intravenous injection of 0.0002 mg/kg no deaths were observed. Toxicity with
repeated administration was not performed because fludeoxyglucose (18F) is
administered in a single dose. This medicinal product is not intended for regular or
continuous administration.
Mutagenecity studies and long-term carcinogenicity studies have not been carried out.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Sodium chloride 9 mg/mL
Water for injections

6.2

Incompatibilities
This medicinal product must not be mixed with other medicinal products
except those mentioned in section 6.6.

6.3

Shelf life

12 hours at the end of the fabrication time.
Date and time of expiry are indicated on the packaging and on the vial.
After first withdrawal, store below 25°C and use within 12 hours without exceeding
the expiry time.
6.4

Special precautions for storage

Store in the original package.
Storage of radiopharmaceuticals should be in accordance with national regulation on
radioactive materials.
For storage conditions after first withdrawal see section 6.3.
6.5

Nature and contents of container

15 mL, colourless glass vial, European Pharmacopoeia Type I, closed with a Teflon
chlorobutyl stopper and an aluminium seal.
Packsize: One multidose vial contains 0.5 to 10 mL of solution, corresponding to 90
to 1850 MBq at calibration time.
6.6

Special precautions for disposal

General warnings
Radiopharmaceuticals should be received, used and administered only by authorised
persons in designated clinical settings. Their 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.
The administration of radiopharmaceuticals creates risks for other persons from
external radiation or contamination from spills of urine, vomiting, etc. Radiation
protection precautions in accordance with national regulations must therefore be
taken.
Any unused medicinal product or waste material should be disposed of in accordance
with local requirements.

7

MARKETING AUTHORISATION HOLDER
IBA PHARMA S.A.
3, Chemin du Cyclotron
1348 OTTIGNIES LOUVAIN-LA-NEUVE
BELGIUM

8

MARKETING AUTHORISATION NUMBER(S)
PL 39950/0001

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION

Date of first authorisation: 31/03/2009

10

DATE OF REVISION OF THE TEXT
02/05/2013

11

DOSIMETRY (IF APPLICABLE)

The data listed below are from ICRP 106 publication.
ABSORBED DOSE PER UNIT ACTIVITY
ORGAN
ADMINISTERED (mGy/MBq)
Adult
15 years 10 years 5 years
0.012
0.016
0.024
0.039
Adrenals
0.13
0.16
0.25
0.34
Bladder
0.011
0.016
0.022
0.034
Bone surfaces
0.038
0.039
0.041
0.046
Brain
0.0088
0.011
0.018
0.029
Breast
0.013
0.016
0.024
0.037
Gall bladder
Gastrointestinal tract
0.011
0.014
0.022
0.035
Stomach
0.016
0.025
0.040
Small Intestine 0.012
0.013
0.016
0.025
0.039
Colon
0.012
0.015
0.024
0.038
(Upper Large
0.014
0.017
0.027
0.041
Intestine
(Lower Large
Intestine
0.067
0.087
0.13
0.21
Heart

1 year
0.071
0.47
0.064
0.063
0.056
0.070
0.067
0.073
0.070
0.070
0.070

0.38

Kidneys
Liver
Lungs
Muscles
Oesophagus
Ovaries
Pancreas
Red marrow
Skin
Spleen
Testes
Thymus
Thyroid
Uterus
Remaining organs
Effective dose
(mSv/MBq)

0.017
0.021
0.020
0.010
0.012
0.014
0.013
0.011
0.0078
0.011
0.011
0.012
0.010
0.018
0.012

0.021
0.028
0.029
0.013
0.015
0.018
0.016
0.014
0.0096
0.014
0.014
0.015
0.013
0.022
0.015

0.029
0.042
0.041
0.020
0.022
0.027
0.026
0.021
0.015
0.021
0.024
0.022
0.021
0.036
0.024

0.045
0.063
0.062
0.033
0.035
0.043
0.040
0.032
0.026
0.035
0.037
0.035
0.034
0.054
0.038

0.078
0.12
0.12
0.062
0.066
0.076
0.076
0.059
0.050
0.066
0.066
0.066
0.065
0.090
0.064

0.019

0.024

0.037

0.056

0.095

The effective dose resulting from the administration of a maximal recommended
activity of 400 MBq of fludeoxyglucose (18F) for an adult weighing 70 kg is about
7.6 mSv.
For an administered activity of 400 MBq, the typical radiation doses delivered to the
critical organs, bladder, heart and brain are respectively: 52 mGy, 27 mGy and 15
mGy, respectively.

12

INSTRUCTIONS FOR PREPARATION OF
RADIOPHARMACEUTICALS (IF APPLICABLE)

Method of preparation
The package must be checked before use and the activity measured using an
activimeter.
The medicinal product may be diluted with sodium chloride 9 mg/mL solution for
injection.
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 authorized automated application system.
If the integrity of this vial is compromised, the product should not be used.
Quality control
The solution should be inspected visually prior to use. Only clear solutions, free of
visible particles should be used.

Detailed information on this medicinal product is available on the website of MHRA.

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Source: Medicines and Healthcare Products Regulatory Agency

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