Ielmag3 0.2 Mg Kit For Radiopharmaceutical Preparation
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
IELMAG3 0.2 mg kit for radiopharmaceutical preparation
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
The kit contains two different vials: (1) and (2).
Vial (1) contains 0.2 mg of the mertiatide ( mercaptoacetyltriglycine).
Vial (2) contains 2.5 mL phosphate buffer solution.
For a full list of excipients, see section 6.1.
The radionuclide is not part of the kit. The kit contains all non radioactive components required for the reconstitution of technetium-(99mTc) mertiatide solution for injection.
3 PHARMACEUTICAL FORM
Kit for radiopharmaceutical preparation. Vial 1: white to off-white powder Vial 2: clear, colourless solution
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
This medicinal product is for diagnostic use only. This is indicated for adults. For paediatric population see section 4.2.
After radiolabelling with sodium pertechnetate(99mTc) solution, the solution of technetium-(99mTc) mertiatide, is used for the evaluation of nephrological and urological disorders in particular for the study of function, morphology and perfusion of the kidneys and characterisation of urinary outflow.
4.2 Posology and method of administration
Posology
Adults and elderly population 40 - 200 MBq, depending on the pathology to be studied and the method to be used.
Population aged less than 18 years
Although IELMAG3 0.2 mg kit for radiopharmaceutical preparation may be used in paediatric patients, formal studies have not been performed. Clinical experience indicates that, for paediatric use, the activity should be reduced. Because of the variable relationship between the size and body weight of patients, it is sometimes more satisfactory to adjust activities to body surface area.
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 to 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 x Multiple The baseline activity is 11,9 MBq.
The minimum activity is 15 MBq.
|
Weight kg |
Multiple |
Weight kg |
Multiple |
|
3 |
1 |
32 |
3.77 |
|
4 |
1.12 |
34 |
3.88 |
|
6 |
1.47 |
36 |
4.00 |
|
8 |
1.71 |
38 |
4.18 |
|
10 |
1.94 |
40 |
4.29 |
|
12 |
2.18 |
42 |
4.41 |
|
14 |
2.35 |
44 |
4.53 |
|
16 |
2.53 |
46 |
4.65 |
|
18 |
2.71 |
48 |
4.77 |
|
20 |
2.88 |
50 |
4.88 |
|
22 |
3.06 |
52-54 |
5.00 |
|
24 |
3.18 |
56-58 |
5.24 |
|
26 |
3.35 |
60-62 |
5.47 |
|
28 |
3.47 |
64-66 |
5.65 |
|
30 |
3.65 |
68 |
5.77 |
Method of administration For intravenous use.
This medicinal product should be reconstituted before administration to the patient. The scintigraphic investigation is usually started immediately after administration. For patient preparation, see section 4.4
For instructions on reconstitution and labelling of the medicinal product before administration, see section 12.
4.3 Contraindications
Hypersensitivity to the active substance, to any of the excipients listed in section 6.1or or to any of the components of the labelled radiopharmaceutical.
4.4 Special warnings and precautions for use
Pregnancy, see section 4.6.
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.
Paediatric population
Paediatric population, see sections 4.2.
Careful consideration of the indication is required since the effective dose per MBq is higher than in adults (see section 11 “Dosimetry”).
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.
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 by the user in a manner which satisfies both radiation safety and pharmaceuticals quality requirements. Appropriate aseptic precautions should be taken.
Specific warnings
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium- free’.
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.
Precautions with respect to environmental hazard see section 6.6.
4.5 Interaction with other medicinal products and other forms of interaction
Technetium-(99mTc) mertiatide is not known to interfere with agents commonly prescribed to patients requiring the above mentioned investigations (e.g. antihypertensives or medicinal agents used to treat or prevent organ transplant rejection).
Under the influence of tubulary secreted hydrochlorothiazide a reduced tubular secretion of the product has to be expected. This can in principle occur with other drugs that are secreted in the proximal tubule (e.g. nonsteroidal anti-inflammatory drugs).
The previous administration of substances such as benzylpenicillin or iodinated contrast media may also cause lower efficiency of the transport mechanism of the tubular cells.
It is reported that co-administration of metoclopramide reduces renal plasma flow. Therapeutic doses may result in reduced clearance values. Dehydration and acidosis can also cause a prolonged elimination of the product.
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 a pregnant woman also involve radiation doses to the foetus.
Only imperative 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 a radioactive medicinal product 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 into breast milk. If the administration is considered necessary, breastfeeding should be interrupted for 24 hours and the expressed feeds discarded.
Moreover, for radioprotection reasons, the mother is recommended to avoid close contact with the baby during the initial 24 hours following injection.
Fertility
Effects on fertility are not known.
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 following table presents how the frequencies are reflected in this section:
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)
Not known (cannot be estimated from the available data)
Very rare mild anaphylactoid reactions have been reported (< 0.01 %), characterised by uriticarial rash, swelling of eyelids and coughing.
Occasionally vasovagal reactions of a mild nature have been reported. A cerebral convulsion in a sedated fifteen days old child has been reported, but causative relation with the administration of the radiopharmaceutical was not proven.
Exposure to ionisation radiation is linked with cancer induction and a potential for development of hereditary defects. For diagnostic nuclear medicine investigations current evidence suggests that these adverse effects might only occur with low frequency because of the low radiation doses incurred.
For most diagnostic nuclear medical procedures, the radiation dose delivered (E) is less than 20 mSv. A worst case calculation for the procedure in question gives values of 2 mSv for an adult and 0.76 mSv for a 1 year old child after injection of 200 and 20 MBq respectively.
Undesirable effects
The attending physician should request the patient to communicate each side effect. 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 national reporting system listed in Appendix V.
4.9 Overdose
In the event of administration of a radiation overdose with technetium-(99mTc) mertiatide the absorbed dose to the patient should be reduced where possible by increasing the elimination of the radionuclide from the body by frequent micturition or 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: radiopharmaceuticals, ATC Code: V09CA03
No pharmaco-dynamic effect is known for technetium-(99mTc) mertiatide at the chemical doses envisaged.
Measuring the counts rate in the kidneys, over time, allows the evaluation of the renal perfusion, function and urinary outflow.
5.2 Pharmacokinetic properties
Distribution
After intravenous injection technetium-(99mTc) mertiatide is rapidly cleared from the blood by the kidneys.
Organ uptake
Technetium-(99mTc) mertiatide binds in a 78-90 % proportion to plasma proteins. In normal renal function 70 % of the administered activity is excreted within 30 min. and more than 95 % within 3 hours. These values are dependent on the pathology of the kidneys and the urogenital system.
Elimination
The mechanism of excretion is predominantly based on tubular secretion. Glomerular filtration accounts for 11 % of total clearance.
5.3 Preclinical safety data
It has been reported that no acute, subacute, subchronic or mutagenic effects have been observed in preclinical studies. However, no detailed information is available for these studies.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
vial (1):
Stannous chloride dihydrate,
Disodium (R,R)-tartrate dihydrate Sodium hydroxide Hydrochloric acid
vial (2):
Sodium monohydrogenphosphate dihydrate Sodium dihydrogenphosphate dihydrate Hydrochloric acid Water for injections
6.2 Incompatibilities
Not known. However, in order not to compromise the stability of technetium-(99mTc) mertiatide, preparations should not be administered together with other drugs.
6.3 Shelf life
Vial (1): 15 months Vial (2): 24 months After radiolabelling: 8 hours.
Store the radiolabelled preparation below 25°C.
6.4 Special precautions for storage
Store in a refrigerator (2 - 8 °C).
Store in the original package in order to protect from light.
For storage conditions of the radiolabelled medicinal product, see section 6.3
Storage of radiopharmaceuticals should be in accordance with national regulations on radioactive material.
6.5 Nature and contents of container
Glass vial (10 mL) closed with a butyl rubber stopper and sealed with an aluminium crimpcap. IELMAG3 0.2 mg kit for radiopharmaceutical preparation is supplied in packages containing five vials with powder (active substance: mertiatide) and five vials with 2.5 mL sterile phosphate buffer solution.
6.6 Special precautions for disposal
The content of the kit before reconstitution is not radioactive. However, after [e.g. sodium pertechnetate (99mTc) Injection, 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.
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.
Contents of the vial are intended only for use in the preparation of technetium (99mTc) mertiatide and are not to be administered directly to the patient without first undergoing the preparative procedure.
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.
For instructions on reconstitution and labelling of the medicinal product before administration, see section 12.
Any unused product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Imaging Equipment Limited
The Barn, Manor Farm, Church Lane
Chilcompton, Radstock BA3 4HP, United Kingdom
Phone: +44 (0) 1761 417402
Fax: +44 (0) 1761 413600
E-Mail: info@imagingequipment.co.uk
8 MARKETING AUTHORISATION NUMBER(S)
PL 35903/0001
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
12/07/2013
10 DATE OF REVISION OF THE TEXT
31/10/2016
11 DOSIMETRY (IF APPLICABLE)
Technetium (99Tc) 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 (99mTc) which, in view of its long half-life of 2.13 x 105 years can be regarded as quasi stable.
The data listed below are from ICRP publication 80 in 1998 and are calculated according to the MIRD system:
The following assumptions have been made in this model:
• In the normal case following intravenous administration of MAG3, the substance is rapidly distributed in the extracellular fluid and excreted entirely by the renal system according to the kidney-bladder model. Total body retention is described by a three-exponential function. The renal transit time is assumed to be 4 minutes as for Hippuran.
• When renal function is bilaterally impaired, it is assumed that the clearance rate of the substance is one tenth of that of the normal case, that the renal transit time is increased to 20 minutes, and that a fraction of 0.04 is taken up in the liver.
• As an example of acute unilateral renal blockage, it is assumed that a fraction of 0.5 of the administered radiopharmaceutical is taken up by one kidney and slowly released to the blood with a half-time of 5 days and subsequently excreted by the other kidney, which is assumed to function normally.
Normal renal function
Absorbed doses: Technetium (99mTc) mertiatide
Dose absorbed per activity administered [mGy/MBq]
|
Organ |
Adults |
15 year old |
10 year old |
5 year old |
1 year old |
|
Adrenals |
0.00039 |
0.00051 |
0.00082 |
0.00120 |
0.00250 |
|
Bladder |
0.11000 |
0.14000 |
0.17000 |
0.18000 |
0.32000 |
|
Bone surfaces |
0.00130 |
0.00160 |
0.00210 |
0.00240 |
0.00430 |
|
Brain |
0.00010 |
0.00013 |
0.00022 |
0.00035 |
0.00061 |
|
Breast |
0.00010 |
0.00014 |
0.00024 |
0.00039 |
0.00082 |
|
Gall bladder |
0.00057 |
0.00087 |
0.00200 |
0.00170 |
0.00280 |
|
GI-tract | |||||
|
Stomach |
0.00039 |
0.00049 |
0.00097 |
0.00130 |
0.00250 |
|
SI |
0.00230 |
0.00300 |
0.00420 |
0.00460 |
0.00780 |
|
Colon |
0.00340 |
0.00430 |
0.00590 |
0.00600 |
0.00980 |
|
ULI |
0.00170 |
0.00230 |
0.00340 |
0.00400 |
0.00670 |
|
LLI |
0.00570 |
0.00700 |
0.00920 |
0.00870 |
0.01400 |
|
Heart |
0.00018 |
0.00024 |
0.00037 |
0.00057 |
0.00120 |
|
Kidneys |
0.00340 |
0.00420 |
0.00590 |
0.00840 |
0.01500 |
|
Liver |
0.00031 |
0.00043 |
0.00075 |
0.00110 |
0.00210 |
|
Lungs |
0.00015 |
0.00021 |
0.00033 |
0.00050 |
0.00100 |
|
Muscles |
0.00140 |
0.00170 |
0.00220 |
0.00240 |
0.00410 |
|
Oesophagus |
0.00013 |
0.00018 |
0.00028 |
0.00044 |
0.00082 |
|
Ovaries |
0.00540 |
0.00690 |
0.00870 |
0.00870 |
0.01400 |
|
Pancreas |
0.00040 |
0.00050 |
0.00093 |
0.00130 |
0.00250 |
|
Red marrow |
0.00093 |
0.00120 |
0.00160 |
0.00150 |
0.00210 |
|
Skin |
0.00046 |
0.00057 |
0.00083 |
0.00097 |
0.00180 |
|
Spleen |
0.00036 |
0.00049 |
0.00079 |
0.00120 |
0.00230 |
|
Testes |
0.00370 |
0.00530 |
0.00810 |
0.00870 |
0.01600 |
|
Thymus |
0.00013 |
0.00018 |
0.00028 |
0.00044 |
0.00082 |
|
Thyroid |
0.00013 |
0.00016 |
0.00027 |
0.00044 |
0.00082 |
|
Uterus |
0.01200 |
0.01400 |
0.01900 |
0.01900 |
0.03100 |
|
Remaining organs |
0.00130 |
0.00160 |
0.00210 |
0.00220 |
0.00360 |
|
Effective dose (mSv/MBq) |
0.00700 |
0.00900 |
0.01200 |
0.01200 |
0.02200 |
|
Bladder wall contributes up to 80% of the effective dose. | |||||
|
Effective dose if the bladder is emptied 1 or |
0.5 hours after administration: | ||||
|
1 hour |
0.00250 |
0.00310 |
0.00450 |
0.00640 |
0.00640 |
|
30 min |
0.00170 |
0.00210 |
0.00290 |
0.00390 |
0.00680 |
Abnormal renal function
Absorbed doses: Technetium (99mTc) mertiatide
Dose absorbed per activity administered [mGy/MBq]
|
Organ |
Adults |
15 year old |
10 year old |
5 year old |
1 year old |
|
Adrenals |
0.00160 |
0.00210 |
0.00320 |
0.00480 |
0.00860 |
|
Bladder |
0.08300 |
0.11000 |
0.13000 |
0.13000 |
0.23000 |
|
Bone surfaces |
0.00220 |
0.00270 |
0.00380 |
0.00500 |
0.00910 |
|
Brain |
0.00061 |
0.00077 |
0.00130 |
0.00200 |
0.00360 |
|
Breast |
0.00054 |
0.00070 |
0.00110 |
0.00170 |
0.00320 |
|
Gall bladder |
0.00160 |
0.00220 |
0.00380 |
0.00460 |
0.00640 |
|
GI-tract | |||||
|
Stomach |
0.00120 |
0.00150 |
0.00260 |
0.00350 |
0.00610 |
|
SI |
0.00270 |
0.00350 |
0.00500 |
0.00600 |
0.01000 |
|
Colon |
0.00350 |
0.00440 |
0.00610 |
0.00690 |
0.01100 |
|
ULI |
0.00220 |
0.00300 |
0.00430 |
0.00560 |
0.00930 |
|
LLI |
0.00510 |
0.00630 |
0.00850 |
0.00860 |
0.01400 |
|
Heart |
0.00091 |
0.00120 |
0.00180 |
0.00270 |
0.00480 |
|
Kidneys |
0.01400 |
0.01700 |
0.02400 |
0.03400 |
0.05900 |
|
Liver |
0.00140 |
0.00180 |
0.00270 |
0.00380 |
0.00660 |
|
Lungs |
0.00079 |
0.00110 |
0.00160 |
0.00240 |
0.00450 |
|
Muscles |
0.00170 |
0.00210 |
0.00290 |
0.00360 |
0.00640 |
|
Oesophagus |
0.00074 |
0.00097 |
0.00150 |
0.00230 |
0.00410 |
|
Ovaries |
0.00490 |
0.00630 |
0.00810 |
0.00870 |
0.01400 |
|
Pancreas |
0.00150 |
0.00190 |
0.00290 |
0.00430 |
0.00740 |
|
Red marrow |
0.00150 |
0.00190 |
0.26000 |
0.00310 |
0.00500 |
|
Skin |
0.00078 |
0.00096 |
0.00150 |
0.00200 |
0.00380 |
|
Spleen |
0.00150 |
0.00190 |
0.00290 |
0.00430 |
0.00740 |
|
Testes |
0.00340 |
0.00470 |
0.00710 |
0.00780 |
0.01400 |
|
Thymus |
0.00074 |
0.00097 |
0.00150 |
0.00230 |
0.00410 |
|
Thyroid |
0.00073 |
0.00095 |
0.00150 |
0.00240 |
0.00440 |
|
Uterus |
0.01000 |
0.01200 |
0.01600 |
0.01600 |
0.02700 |
|
Remaining organs |
0.00170 |
0.00210 |
0.00280 |
0.00340 |
0.00600 |
|
Effective dose (mSv/MBq) |
0.00610 |
0.00780 |
0.01000 |
0.01100 |
0.19000 |
Acute unilateral renal blockage Absorbed doses: Technetium (99mTc) mertiatide
Dose absorbed per activity administered [mGy/MBq]
|
Organ |
Adults |
15 year old |
10 year old |
5 year old |
1 year old |
|
Adrenals |
0.01100 |
0.01400 |
0.02200 |
0.03200 |
0.05500 |
|
Bladder |
0.05600 |
0.07100 |
0.09100 |
0.09300 |
0.17000 |
|
Bone surfaces |
0.00310 |
0.00400 |
0.00580 |
0.00840 |
0.01700 |
|
Brain |
0.00011 |
0.00014 |
0.00023 |
0.00039 |
0.00075 |
|
Breast |
0.00038 |
0.00051 |
0.00100 |
0.00160 |
0.00300 |
|
Gall bladder |
0.00620 |
0.00730 |
0.01000 |
0.01600 |
0.02300 |
|
GI-tract | |||||
|
Stomach |
0.00390 |
0.00440 |
0.00700 |
0.00930 |
0.01200 |
|
SI |
0.00430 |
0.00550 |
0.00850 |
0.01200 |
0.01900 |
|
Colon |
0.00390 |
0.00500 |
0.00720 |
0.00920 |
0.00150 |
|
ULI |
0.00400 |
0.00510 |
0.00760 |
0.01000 |
0.01600 |
|
LLI |
0.00380 |
0.00480 |
0.00670 |
0.00820 |
0.01300 |
|
Heart |
0.00130 |
0.00160 |
0.00270 |
0.00400 |
0.00610 |
|
Kidneys |
0.20000 |
0.24000 |
0.33000 |
0.47000 |
0.81000 |
|
Liver |
0.00440 |
0.00540 |
0.00810 |
0.01100 |
0.01700 |
|
Lungs |
0.00110 |
0.00160 |
0.00250 |
0.00390 |
0.00720 |
|
Muscles |
0.00220 |
0.00270 |
0.00370 |
0.00510 |
0.00890 |
|
Oesophagus |
0.00038 |
0.00054 |
0.00085 |
0.00150 |
0.00230 |
|
Ovaries |
0.00380 |
0.00510 |
0.00710 |
0.00920 |
0.01500 |
|
Pancreas |
0.00740 |
0.00900 |
0.01300 |
0.01800 |
0.02900 |
|
Red marrow |
0.00300 |
0.00360 |
0.00500 |
0.00600 |
0.00830 |
|
Skin |
0.00082 |
0.00100 |
0.00150 |
0.00220 |
0.00420 |
|
Spleen |
0.00980 |
0.01200 |
0.01800 |
0.02600 |
0.04000 |
|
Testes |
0.00200 |
0.00290 |
0.00450 |
0.00500 |
0.00980 |
|
Thymus |
0.00038 |
0.00054 |
0.00085 |
0.00150 |
0.00230 |
|
Thyroid |
0.00017 |
0.00023 |
0.00045 |
0.00092 |
0.00160 |
|
Uterus |
0.00720 |
0.00870 |
0.01200 |
0.01300 |
0.02200 |
|
Remaining organs |
0.00210 |
0.00260 |
0.00360 |
0.00470 |
0.00800 |
Effective dose (mSv/MBq)
The effective dose resulting from the administration of a maximal recommended activity of 200 MBq for an adult weighing 70 kg is about 1.4 mSv.
For an administered activity of 200 MBq the typical radiation dose to the target organ (kidney) is 0.68 mGy and the typical radiation dose to the critical organ bladder wall is 21.6 mGy.
12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS (IF APPLICABLE)
Radiolabelling should be done using an eluate with a radioactive concentration between 40 and 1250 MBq/mL. Only eluates obtained from a generator, which has been eluted once in the preceding 24 hours, should be used. Dilution of the preparation should be done with saline.
The content of vial (1) is labelled with sodium pertechnetate (99mTc) solution at room temperature. The radiolabelling reaction is stopped after 15 minutes by adding the buffer solution.
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.
As with any pharmaceutical product, if at any time in the preparation of this product the integrity of this vial is compromised it should not be used.
Method of preparation
The radiopharmaceutical is prepared according to the following labelling instructions immediately before use:
The radiolabelling procedure has to be carried out under aseptic conditions.
Place vial (1) into an adequate lead shielding. Swab the rubber septum with an appropriate disinfectant and let it dry.
Inject 2 mL of sodium pertechnetate (99mTc) solution into vial (1) using a syringe. Then withdraw the same volume of nitrogen from the vial with the same syringe for pressure compensation.
Shake the vial carefully in order to moisten. The complete content of the vial is for complete dissolution of any powder.
After 15 minutes reaction time transfer a volume of 2 mL buffer solution from vial (2) into vial (1) using a new syringe. Then withdraw the same volume of nitrogen from the vial with the same syringe for pressure compensation.
Shake carefully for good mixing. Determine the total radioactivity and calculate the volume to be injected.
If necessary, dilute with sterile isotonic saline up to a final total volume of 10 mL. Shake again for good mixing.
Properties of the product after radiolabelling:
Appearance: Clear to slightly opalescent, colourless, aqueous solution.
pH: 7.1-7.5
Quality control
The following methods may be used:
HPLC method
The radiochemical purity of the labelled substance is examined by high performance liquid chromatography (HPLC) using a suitable detector of radioactivity, on a 25 cm RP18 column, flow rate 1.0 mL/min. Mobile phase A is a 93:7 mixture of phosphate solution (1.36 g KH2PO4, adjusted with 0.1 M NaOH to pH 6) and ethanol. Mobile phase B is a 1:9 mixture of water and methanol.
Use a gradient elution program with the following parameters:
|
Time (min): |
Flow (mL/min): |
% A |
% B |
|
10 |
1 |
100 |
0 |
|
15 |
1 |
0 |
100 |
The technetium-(99mTc) mertiatide peak appears at the end of the passage of mobile phase A.
The injection volume is 10 pl and the total count rate per channel must not exceed 30.000.
Specification:
|
t = 0 |
after 6 hours | |
|
technetium-(99mTc) mertiatide |
> 94 % |
> 94 % |
|
hydrophilic impurities |
< 3.0 % |
< 3.0 % |
|
lipophilic impurities |
< 4.0 % |
< 4.0 % |
Simplified rapid procedure
This method is based on cartridges, which are widely used as sample pre-treatment of aqueous solutions for chromatography. The cartridge (e.g. Sep-Pak Plus C 18,
Waters) is washed with 10 mL absolute ethanol, followed by 10 mL 0.001 M hydrochloric acid. Remaining residues of the solutions are removed by 5 mL of air.
0.05 mL technetium-(99mTc) mertiatide solution is applied on the cartridge. Elute with 10 mL of 0.001 M hydrochloric acid and collect this first eluate (hydrophilic impurities). Elute the cartridge with ethanol/ 9 g/L sodium chloride solution in a ratio of 1:1. This second eluate contains technetium-(99mTc) mertiatide. The cartridge contains the lipophilic impurities.
Measure the radioactivity of each portion. Sum up the radioactivity of the eluates and the cartridge as 100 % and calculate the respective percentages.
Be aware to elute slowly (drop wise).
Specification: technetium-(99mTc) mertiatide > 94 % Sum of impurities: < 6.5 %
Detailed information on this product is available on the website of the European Medicines Agency http://www.ema.europa.eu