Technescan DTPA 20.8 mg kit for radiopharmaceutical preparation – patient leaflet, side effects, dosage

1. What Technescan DTPA is and what it is

used for

This medicine is a radiopharmaceutical product for diagnostic use only.

Technescan DTPA is used through a scan to examine the:

• kidneys,
• brain,
• lungs,
• gastroesophageal reflux and gastric emptying.

This medicine is a non-radioactive powder. When mixed by qualified people, with a solution of the radioactive substance, sodium pertechnetate (^99mTc) it forms Technetium (^99mTc) pentetate. When administered into the body it collects in certain organs such as, the kidneys or the brain.

The radioactive substance can be photographed (scanned) from outside the body, using special cameras which take a scan. This scan shows the distribution of radioactivity within the organ and body. This also gives the doctor valuable information about the structure and function of that organ.

The use of Technescan DTPA does involve exposure to small amounts of radioactivity. Your doctor and the nuclear medicine doctor have considered that the clinical benefit that you will obtain from the procedure with the radiopharmaceutical outweighs the risk due to radiation.

2. What you need to know before

Technescan DTPA is used

Technescan DTPA must not be used

• if you are allergic (hypersensitive) to pentetic acid or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

• You must not be given this medicine in the spinal canal and brain space, known as the subarachnoid space.

Take special care with Technescan DTPA

• if you are pregnant or believe you may be pregnant
• if you are breast-feeding

Before administration of Technescan DTPA 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. This will prevent active substance gathering in the bladder.
• Tell your doctor if you have symptoms of decreased kidney function

Children and adolescents

Talk to your nuclear medicine doctor if you are under 18 years old.

Other medicines and Technescan DTPA

Tell your nuclear medicine doctor if you are taking, have recently taken or might take any other medicines.

The following medicines may specifically interfere with the results of the examination with Technescan DTPA:

• Medicines interfering with renal imaging:

  • medicines to treat high blood pressure, for example, medications with active substance with names ending in “pril” such as captopril
  • medicines to treat inflammatory disease such as diclofenac
  • medicines that stimulate water clearance from the body, such as furosemide or hydrochlorothiazide

  • medicines which may affect your renal function, such as:

    • medicines to treat infection (antibiotics), such as aminoglycosides
    • medicines to treat tumours such as cisplatin
    • contrast media for radiographic imaging

• Medicines interfering with gastric emptying

  • acute pain-relieving medications such as morphine
  • medicines to treat Parkinson’s disease such as levodopa
  • medicines to prevent or alleviate nausea and vomiting such as metoclopramide,
  • medicines that neutralise stomach acid such as aluminium antacids
  • medicines to treat ulcers such as propantheline

• Medicines interfering with brain imaging:

  • medicines which influence mood, emotional state and disposition

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

You must inform the nuclear medicine doctor before the administration of Technescan DTPA 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

  Your nuclear medicine doctor will only administer this product during pregnancy if a benefit is expected which would outweigh the risks.

• If you are breast-feeding

  Tell your doctor if you are breast-feeding as he/she may delay the study until breast-feeding is finished. Your doctor may also ask you to stop breast-feeding for 12 hours and discard this milk, until the radioactivity is no longer in your body. Please ask your nuclear medicine doctor when you can resume breast-feeding.

Driving and using machines

It is considered unlikely that Technescan DTPA will affect the ability to drive and operate machinery.

3. How Technescan DTPA is used

There are strict laws on the use, handling and disposal of radiopharmaceutical products. Technescan DTPA will only be used in special controlled settings ( hospital or similar). This product will only be handled and given to you by people who are trained and qualified to use it safely. These persons will take special care for the safe use of this product and will keep you informed of their actions.

The nuclear medicine doctor supervising the procedure will decide on the quantity of Technescan DTPA to be used in your case. The dose administered will depend on the procedure you are undergoing and other factors such as the method of administration. It will be the smallest quantity necessary to get the desired information.

The quantity to be administered usually recommended for an adult ranges from 7 to 1000 MBq ( mega Becquerel, the unit used to express radioactivity).

Use in children and adolescents

In children and adolescents, the quantity to be administered will be adapted to the child’s weight.

Administration of Technescan DTPA and conduct of the procedure

Technescan DTPA is injected into a vein for imaging the kidneys or the brain, is taken orally for stomach or oesophagus investigations and is inhaled for lung examinations. A single administration is usually sufficient.

Duration of the procedure

Your nuclear medicine doctor will inform you about the usual duration of the procedure.

After administration of Technescan DTPA, 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 have been given more Technescan DTPA than you should

An overdose is unlikely because you will only receive a single dose of Technescan DTPA precisely controlled by the nuclear medicine doctor supervising the procedure. However, in case of an overdose, you will receive the appropriate treatment.

Should you have any further questions on the use of this product, please ask the nuclear medicine doctor who supervises the procedure.

4. Possible side effects

Like all medicines, Technescan DTPA can cause side effects, although not everybody gets them.

The following side effects can occur (the frequency of occurrence cannot be estimated from the available data).

• widening of the blood vessels which causes sudden redness of the skin,
• dizziness,
• shortness of breath (dyspnoea),
• itchiness,
• hives (urticaria),
• low blood pressure (hypotension)

This radiopharmaceutical will deliver low amounts of ionizing radiation associated with the least risk of cancer and hereditary abnormalities.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

5. How Technescan DTPA is stored

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.

The following information is intended for the specialist only.

Technescan DTPA must not be used after the expiry date which is stated on the label on the vial after EXP. The expiry date refers to the last day of the month. Technescan DTPA must not be used if there are visible signs of deterioration.

6. Contents of the pack and other

information

What Technescan DTPA contains

• The active substance is: pentetic acid.

  Each vial contains 20.8 mg of pentetic acid.

• The other ingredients are: gentisic acid, stannous chloride dihydrate, calcium chloride dihydrate, sodium hydroxide, hydrochloric acid.

What Technescan DTPA looks like and contents of the pack

Technescan DTPA is an off-white slightly yellow freeze-dried powder for solution for injection. It is packaged in 10 ml glass vials closed with a bromobutyl rubber cap, sealed with an aluminium cap.

Technescan DTPA is supplied in one pack containing 5 vials.

Marketing Authorisation Holder and Manufacturer

Curium Netherlands B.V.

Westerduinweg 3

1755 LE Petten, The Netherlands

PL 12288/0011

This leaflet was last revised in February 2023.

The following information is intended for medical or healthcare professionals only:

The complete SmPC of Technescan DTPA is provided as a separate document in the product package, with the objective to provide healthcare professionals with other additional scientific and practical information about the administration and use of this radiopharmaceutical.

Please refer to the SmPC included in the box.

SUMMARY OF PRODUCT CHARACTERISTICS

1. 1. NAME OF THE MEDICINAL PRODUCT

Technescan DTPA 20.8 mg, kit for radiopharmaceutical preparation

1. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains 20.8 mg Pentetic acid.

To be reconstituted with sodium pertechnetate (^99mTc) for the preparation of the diagnostic agent: Technetium (^99mTc) pentetate. The radionuclide is not part of the kit.

For the full list of excipients, see section 6.1.

1. 3. PHARMACEUTICAL FORM

Kit for radiopharmaceutical preparation.

Off-white to slightly yellow freeze-dried powder for solution for injection, oral use or inhalation.

1. 4. CLINICAL PARTICULARS

4.1 Therapeutic indications

This medicinal product is for diagnostic use only.

After reconstitution with sodium pertechnetate (^99mTc) solution, the solution of technetium (^99mTc) pentetate is indicated for:

a. After intravenous administration for:

• Measurement of glomerular filtration rate
• Renal perfusion and function and urinary tract studies

• Cerebral angioscintigraphy (as an alternative method when

  computed tomography and/or magnetic resonance imaging are not available).

b. After inhalation of the nebulized technetium (^99mTc) pentetate for:

• Lung ventilation imaging

c. After oral administration of the technetium (^99mTc) pentetate for:

• Detection of gastroesophageal reflux and liquid gastric

  emptying study.

4.2 Posology and Method of Administration

Posology

Adults and the elderly population

The following administered activities are recommended (other activities may be justifiable):

Intravenous use:

• Measurement of glomerular filtration rate from plasma: 7 - 18 MBq.
• Renal scintigraphy: 40 - 400 MBq.
• Cerebral angioscintigraphy: 185 - 740 MBq.

For inhalation:

Lung ventilation imaging:

• 500-1000 MBq deposited in the nebuliser
• 50-100 MBq in the lung.

For oral use:

• Detection of gastroesophageal reflux and gastric emptying study:

  10 - 20 MBq.

• Technetium (^99mTc) pentetate is mixed with an appropriate volume

  (30 to 240 mL) of liquid carrier (e.g. milk).

Renal/hepatic impairment

Careful consideration of the activity to be administered is required since an increased radiation exposure is possible in these patients (see section 4.4).

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 by intravenous route to children and to adolescents may be calculated according to the recommendations of the European Association of Nuclear Medicine EANM (2016) paediatric dosage card, by using the formula corresponding to the concerned indication and the relevant correction factor corresponding to the body mass of the young patient.

• Administration of technetium (^99mTc) pentetate in abnormal renal function:

  Administered Activity[MBq] = Baseline Activity x Multiple

  (with a baseline activity of 14.0)

  Table 1

In very young children (up to 1 year), when technetium (^99mTc) pentetate is used for urinary tract examinations, a minimum dose of 20 MBq is necessary to obtain images of sufficient quality.

• Administration of technetium (^99mTc) pentetate in normal renal function:

  Administered Activity[MBq] = Baseline Activity x Multiple

  (with a baseline activity of 34.0)

  Table 2

• Lung ventilation imaging: 500 - 1000 MBq deposited in the nebuliser; 10 MBq in the lung.
• Detection of gastroesophageal reflux and liquid gastric emptying study: 10 - 20 MBq. Administered activity of the radiopharmaceutical and the volume to be fed to the patient should be based on patient factors such as age, body weight, and the usual feeding volume. Administered activity for children should be as low as reasonably achievable for diagnostic image quality.

Method of administration

For intravenous, inhalation and oral administration.

For multidose use.

This medicinal product should be reconstituted before administration to the patient.

For instructions on reconstitution and radiolabelling of the medicinal product before administration, see section 12.

For patient preparation, see section 4.4.

Image acquisition

• Renal perfusion imaging is obtained by dynamic acquisitions immediately after injection up to 1 minute. The optimal static imaging time is 1hour post injection. In case of captopril (ACE inhibitor) renography, captopril is given intravenously before technetium (^99mTc) pentetate administration. Individual kidney function and urinary outflow imaging are obtained by dynamic acquisitions performed after injection. If one or both kidneys have not emptied satisfactorily during the first 20 minutes, a furosemide challenge is performed, and the dynamic acquisition should continue for a further 15-minute after the diuretic. Static images may be acquired 1 hour after injection.
• For cerebral examinations, dynamic acquisitions should begin immediately after injection. Static images are obtained 1 hour and, if necessary, several hours after injection.
• For lung ventilation imaging: images of the lungs are obtained during 180 min.
• Dynamic images of oesophagus are obtained during the first minutes after administration followed by continuous imaging for 60 minutes for evaluation of gastroesophageal reflux. Gastric emptying at 60 minutes and at 2 or 3 hours after completion of feeding is calculated.

4.3 Contra-indications

Hypersensitivity to the active substance, or to any of the excipients listed in section 6.1 or to any of the components of the labelled radiopharmaceutical.

4.4 Special warnings and special 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 medicinal 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 administrated should in every case be as low as reasonably achievable to obtain the required diagnostic information.

Renal/ hepatic impairment

Careful consideration of the benefit risk ratio in these patients is required since an increased radiation exposure is possible.

Paediatric population

For information on use in the paediatric population, see section 4.2. Careful consideration of the indication is required since the effective dose per MBq is higher than in adults (see section 11).

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 exposure.

Special warnings

Technescan DTPA injection solution should not be administered in the subarachnoid space and should never be used for scintigraphy of the cerebrospinal flow.

Depending on the time when you administer the injection, the content of sodium given to the patient may in some cases be greater than 1mmol. This should be taken into account in patients on low sodium diet.

Precautions with respect to environmental hazard see section 6.6.

4.5 Interactions with other medicinal products and other forms of interaction

Many drugs may affect the function of tested organ and modify the uptake of technetium (^99mTc) pentetate.

During renal scintigraphy

A single administration of a diuretic or ACE inhibitor is sometimes used during pharmacological tests in the differential diagnosis of nephrological and urological disorders.

ACE inhibitors reduce renal blood flow.

Diclofenac, furosemide and other diuretics such as hydrochlorothiazide, may affect renal excretion and thereby influence the technetium (^99mTc) pentetate clearance.

Nephrotoxic drugs such as aminoglycosides, cisplatin and administered contrast media can reduce the renal excretion and thereby influence the technetium (^99mTc) pentetate clearance.

During gastroesophageal scintigraphy and gastric emptying

• Morphine and levodopa delay gastric emptying.

• Metoclopramide may stimulate gastric emptying and decrease

  significantly the small intestine transit time.

• Aluminium antacids and propantheline may prolong the gastric

  emptying.

During cerebral angioscintigraphy

Psychotropic medications increase blood flow in the area of the external carotid artery. This may lead to the rapid uptake of the radioactive product in the nasopharyngeal area during the arterial and capillary phases (“hot nose” phenomenon).

4.6 Fertility, pregnancy and lactation

Woman of childbearing potential

When 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.

Breast-feeding

Before administering radiopharmaceuticals to a mother who is breast-feeding, consideration should be given to the possibility of delaying the administration of radionuclide until the mother has ceased breast-feeding 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, the breast-feeding should be interrupted for 12 hours and the expressed feeds discarded.

Fertility

No study on fertility has been performed.

4.7 Effects on ability to drive and use machines

Technetium (^99mTc) pentetate has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

The adverse events are presented in the table below by system organ classes and with a not known frequency (cannot be estimated from the available data).

Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. As the effective dose is 3.6 mSv when the maximal recommended activity of 740 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 Yellow Card Scheme

Website: https://yellowcard.mhra.gov.uk/

4.9 Overdose

In the event of the administration of a radiation overdose with technetium (^99mTc) pentetate 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.

1. 5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Diagnostic radiopharmaceuticals for the renal and respiratory systems, Technetium (^99mTc) compounds. ATC code: V09C A01; V09E A01

Mechanism of action:

• Technetium(^99mTc) pentetate, like inulin, circulates in blood with negligible binding to plasma proteins. It is filtered through the glomerular membrane and undergoes no tubular secretion or reabsorption It does not cross the normal blood-brain barrier (BBB).
• Technetium (^99mTc) pentetate is aerosolised from a water solution with a particle size of 1.2 - 2 micrometer. After inhalation aerosol droplets are distributed and deposited within airways and alveoli depending on their aerodynamic properties, particularly their mass median aerodynamic diameter.
• Following oral administration, technetium (^99mTc) pentetate does not pass through the digestive barrier (non-absorbable). Mixed with the meal, technetium (^99mTc) pentetate follows digestive transit.

Pharmacodynamic effects: At the concentrations and activities such as those used for diagnosis, ^99mTc pentetate does not appear to have any pharmacodynamic activity.

5.2 Pharmacokinetic properties

Distribution

Following intravenous injection, technetium (^99mTc) pentetate rapidly distributes throughout the extracellular fluid. Less than 5% of the injected dose is bound to the plasma proteins. There is also a negligible binding of technetium (^99mTc) pentetate to red blood cells. Technetium (^99mTc) pentetate does not cross the normal blood-brain barrier but diffuse weakly in breast milk.

In patients exhibiting oedema or ascites, distribution of the radioisotope in the extracellular spay may be modified.

In lung ventilation studies, after inhalation, technetium (^99mTc) pentetate diffuses rapidly from the pulmonary alveoli towards the vascular space where it is diluted. Many factors are likely to modify the permeability of the pulmonary epithelium like cigarette smoking.

Following oral administration, technetium (^99mTc) pentetate does not pass through the digestive barrier.

Elimination

Plasma clearance is multi-exponential with an extremely fast component. The complex remains stable in vivo, more than 98% of urine radioactivity is in the form of a chelate.

Approximately 90% of the injected dose is eliminated in the urine within the first 24 hours mainly by glomerular filtration. No retention of the compound has been demonstrated in the kidneys.

Half-life

The physical half-life of technetium (^99mTc) is 6.01 hours. The half-life of technetium (^99mTc) pentetate in the lungs is slightly less than 1 hour.

Renal/Hepatic impairment

Plasma clearance may be delayed in patients with renal disease. The pharmacokinetics in patients with hepatic impairment has not been characterised.

5.3 Preclinical safety data

This agent is not intended for regular or continuous administration. Repeated intravenous administration of CaNa₃DTPA to rabbits and dogs for 14 days of doses that were 100 and 1000 times (respectively) the normal dose for human, produced no evidence of toxicity. The minimum dose of CaDTPA causing abortion and foetal death in mice was approximately 3600 times the dose of CaNa₃DTPA that is proposed for diagnosis in women. Mutagenicity studies and long-term carcinogenicity studies have not been carried out.

1. 6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Gentisic acid

Stannous chloride dihydrate

Calcium chloride dihydrate

Sodium hydroxide

Hydrochloric acid (for pH adjustment)

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in section 12.

6.3 Shelf life

1 year when stored below 25°C.

The expiry date is stated on the label of each vial and on the carton box. After radiolabelling: 8 hours when stored below 25°C.

6.4 Special Precautions for Storage

Keep the vials in the outer carton.

For storage conditions after radiolabelling of the medicinal product, see section 6.3.

Storage of radiopharmaceuticals should be in accordance with the national regulations on radioactive materials.

6.5 Nature and contents of container

Carton box containing 5 glass vials of 10 mL (Type 1 Ph Eur) closed with a bromobutyl rubber lyophilisation stopper sealed with an aluminium cap.

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. 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 kit are intended only for use in the preparation of technetium (^99mTc) pentetate 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) 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 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.

1. 7. MARKETING AUTHORISATION HOLDER

Curium Netherlands B.V.

Westerduinweg 3

1755 LE Petten

Netherlands

1. 8. MARKETING AUTHORISATION NUMBER

PL 12288/0011

1. 9. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION

21 March 2001

1. 10. DATE OF REVISION OF THE TEXT

10/02/2023

1. 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 6.01 hours to (⁹⁹Tc) technetium, 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 128 and are calculated according to the following assumptions:

• Intravenous administration of technetium (^99mTc) pentetate gives rise to an initial distribution in the extracellular fluid. Following this initial distribution phase, the substance is excreted exclusively by the renal system. In case of normal renal function, total body retention is described by a bi-exponential function with component half-times of 100 min (0.99) and 7 days (0.01). The fraction excreted by the kidneys is 1.0 (1.0), and the renal transit time is 5 min. In case of abnormal renal function, it is assumed that the retention half-time of the major component is 1000 min, and the renal transit time is increased to 20 min.

According to the provisions of the International Commission of Radiological Protection (ICRP 128), the radiation doses absorbed by the patient after intravenous injection are the following:

Normal renal function

Absorbed dose per unit activity administered

(mGy/MBq)

Organ

Adult 15 years 10 years 5 years 1 year

Adrenals 0.0014 0.0018 0.0027 0.004 0.0072 Bone surfaces 0.0024 0.0029 0.0043 0.0061 0.010 Brain 0.00086 0.0011 0.0017 0.0028 0.0049 Breast 0.00072 0.00092 0.0013 0.0022 0.0041 Gallbladder 0.0015 0.0021 0.0038 0.005 0.0061 Gastrointestinal tract Stomach wall 0.0013 0.0017 0.0028 0.0040 0.0068 Small intestine wall 0.0025 0.0031 0.0049 0.0070 0.010 Colon wall 0.0031 0.0039 0.0060 0.0081 0.011 Upper large intestine wall 0.0021 0.0028 0.0043 0.0065 0.0092 Lower large intestine wall 0.0043 0.0054 0.0082 0.010 0.013 Heart wall 0.0012 0.0015 0.0022 0.0033 0.0059 Kidneys 0.0044 0.0053 0.0075 0.011 0.018 Liver 0.0012 0.0016 0.0025 0.0038 0.0064 Lungs 0.001 0.0013 0.002 0.003 0.0055 Muscles 0.0016 0.002 0.003 0.0043 0.0068 Ovaries 0.0042 0.0053 0.0077 0.01 0.013 Pancreas 0.0014 0.0018 0.0028 0.0043 0.0074 Red marrow 0.0015 0.0018 0.0027 0.0037 0.0057 Skin 0.00087 0.001 0.0017 0.0026 0.0044 Spleen 0.0013 0.0016 0.0026 0.0039 0.0068 Testes 0.0029 0.004 0.0068 0.0094 0.013 Thymus 0.001 0.0013 0.0019 0.0030 0.0054 Thyroid 0.001 0.0013 0.0021 0.0033 0.006 Urinary bladder wall 0.062 0.078 0.11 0.15 0.17 Uterus 0.0079 0.0096 0.015 0.018 0.022 Remaining organs

0.0017 0.0021 0.0030 0.0042 0.0066 Effective dose

(mSv/MBq) 0.0049 0.0063 0.0094 0.012 0.016

The effective dose resulting from the administration of a maximal recommended activity of 740 MBq for an adult weighing 70 kg is about 3.6 mSv.

For an administered activity of 740 MBq the typical radiation dose to the target organ (kidneys) is 3.3 mGy and the typical radiation dose to the critical organ (urinary bladder wall) is 46 mGy.

Abnormal renal function

Absorbed dose per unit activity administered

(mGy/MBq)

Organ

Adult 15 years 10 years 5 years 1 year

Adrenals 0.0041 0.0051 0.0076 0.011 0.021 Bone surfaces 0.006 0.0071 0.011 0.015 0.028 Brain 0.0028 0.0035 0.0057 0.0091 0.016 Breast 0.0023 0.003 0.0042 0.0068 0.013 Gallbladder wall 0.0042 0.0057 0.0092 0.013 0.016 Gastrointestinal tract Stomach wall 0.0038 0.005 0.0079 0.011 0.019 Small intestine wall 0.0045 0.0056 0.0085 0.013 0.022 Colon wall 0.0045 0.0058 0.0087 0.013 0.022 Upper large intestine wall 0.0043 0.0056 0.0081 0.013 0.021 Lower large intestine wall 0.0049 0.0061 0.0095 0.013 0.023 Heart wall 0.0037 0.0047 0.007 0.01 0.018 Kidneys 0.0077 0.0092 0.013 0.019 0.032 Liver 0.0037 0.0046 0.0071 0.011 0.019 Lungs 0.0033 0.0042 0.0062 0.0095 0.017 Muscles 0.0032 0.004 0.0061 0.0091 0.017 Ovaries 0.005 0.0062 0.0092 0.014 0.023 Pancreas 0.0043 0.0053 0.008 0.012 0.021 Red marrow 0.0034 0.0042 0.0064 0.0093 0.016 Skin 0.0022 0.0026 0.0042 0.0067 0.012 Spleen 0.0038 0.0047 0.0073 0.011 0.019 Testes 0.0035 0.0045 0.0069 0.01 0.018 Thymus 0.0033 0.0042 0.0062 0.0096 0.017 Thyroid 0.0034 0.0042 0.0067 0.011 0.019 Urinary bladder wall 0.021 0.027 0.039 0.05 0.066 Uterus 0.0061 0.0074 0.011 0.016 0.025 Remaining organs

0.0033 0.0041 0.0063 0.0097 0.017 Effective dose

(mSv/MBq) 0.0046 0.0058 0.0087 0.013 0.021

The physical half-life of ^99mTc is 6.01 h.

The urinary bladder wall contributes up to 57% of the effective dose.

The data listed below are from ICRP 53 and are calculated according to the following assumptions:

• Inhalation of technetium (^99mTc) pentetate

  Inhalation of aerosol consisting of particles smaller than 2-3 micrometer in diameter results in deposition mainly in the alveoli. Particles are rapidly cleared from the lungs via the blood stream. The biological half-life of technetium (^99mTc) pentetate in the lungs is 60-80 minutes in normal non-smokers; it is shortened in smokers and in most patients with lung disease. A value of 60 min is adopted below. Substance reaching the blood is eliminated according to the model for intravenously administered technetium (^99mTc) pentetate.

According to ICRP 53 the radiation doses given to a man on administration by aerosol technetium (^99mTc) pentetate are:

Absorbed dose per unit activity administered

(mGy/MBq)

Organ

Adult 15 years 10 years 5 years 1 year

Adrenals 0.0021 0.0029 0.0044 0.0067 0.012 Bladder wall 0.047 0.058 0.084 0.12 0.23 Bone surfaces 0.0019 0.0024 0.0035 0.0053 0.0098 Breast 0.0019 0.0019 0.0033 0.0048 0.0078 Gastrointestinal tract Stomach wall 0.0017 0.0022 0.0035 0.0051 0.0089 Small intestine wall 0.0021 0.0026 0.0041 0.0063 0.011 Upper large intestine wall 0.0019 0.0024 0.0038 0.0061 0.01 Lower large intestine wall 0.0032 0.0042 0.0063 0.0088 0.015 Kidneys 0.0041 0.0051 0.0072 0.011 0.019 Liver 0.0019 0.0025 0.0037 0.0055 0.0097 Lungs 0.017 0.026 0.036 0.054 0.1 Ovaries 0.0033 0.0041 0.0061 0.0089 0.015 Pancreas 0.0021 0.0026 0.004 0.0061 0.011 Red marrow 0.0027 0.0034 0.0047 0.0062 0.0096 Spleen 0.0019 0.0024 0.0036 0.0056 0.0099 Testes 0.0021 0.0031 0.0052 0.0079 0.015 Thyroid 0.00099 0.0017 0.0027 0.0044 0.0078 Uterus 0.0059 0.0072 0.011 0.016 0.027 Other tissues

0.0018 0.0022 0.0032 0.0049 0.0086 Effective dose

equivalent (mSv/MBq) 0.007 0.0091 0.013 0.02 0.036

The effective dose equivalent resulting from the inhalation of a maximal recommended activity of 100 MBq for an adult weighing 70 kg is about 0.7 mSv.

For an inhalated activity of 100 MBq the typical radiation dose to the target organ (lungs) is 1.7 mGy and the typical radiation dose to the critical organ (urinary bladder wall) is 4.7 mGy.

The data listed below are from ICRP 128 and are calculated according to the following assumptions:

• Oral administration of technetium (^99mTc) pentetate

  Technetium (^99mTc) pentetate is considered as non-absorbable marker in studies of the gastrointestinal tract. The gastric residence time is fixed to 33 min for fluids.

The radiation doses given to a man on oral administration of technetium (^99mTc) pentetate are the following:

Oral administration of fluids

Absorbed dose per unit activity administered

(mGy/MBq)

Organ

Adult 15 years 10 years 5 years 1 year

Adrenals 0.0025 0.0033 0.0055 0.0089 0.015 Bone surfaces 0.0042 0.0052 0.0074 0.011 0.021 Brain 0.0000018 0.0000034 0.000012 0.00004 0.0001 Breast 0.00028 0.00042 0.00094 0.002 0.0038 Gallbladder 0.014 0.018 0.03 0.043 0.071 Gastrointestinal tract Stomach wall 0.022 0.029 0.041 0.066 0.12 Small intestine wall 0.06 0.076 0.12 0.19 0.35 Colon wall 0.1 0.13 0.22 0.35 0.66 Upper large intestine wall 0.12 0.15 0.25 0.4 0.75 Lower large intestine wall 0.083 0.11 0.18 0.29 0.54 Heart wall 0.001 0.0014 0.0025 0.0043 0.0086 Kidneys 0.0055 0.0067 0.01 0.015 0.023 Liver 0.0037 0.0048 0.0093 0.015 0.027 Lungs 0.00057 0.00091 0.0016 0.0029 0.0057 Muscles 0.0032 0.004 0.006 0.009 0.015 Oesophagus 0.00019 0.0003 0.0005 0.0012 0.0026 Ovaries 0.025 0.032 0.048 0.068 0.11 Pancreas 0.0059 0.0079 0.012 0.018 0.031 Red marrow 0.0047 0.0057 0.0075 0.0092 0.011 Skin 0.00093 0.0011 0.0017 0.0029 0.0054 Spleen 0.004 0.005 0.0078 0.012 0.02 Testes 0.0013 0.002 0.0038 0.0065 0.012 Thymus 0.00019 0.0003 0.0005 0.0012 0.0026 Thyroid 0.00002 0.000048 0.00015 0.0003 0.0012 Urinary bladder wall 0.0069 0.0091 0.014 0.022 0.035 Uterus 0.016 0.02 0.031 0.047 0.076 Remaining organs

0.0052 0.0072 0.011 0.02 0.03 Effective dose

(mSv/MBq) 0.019 0.025 0.039 0.062 0.11

The effective dose equivalent resulting from the oral administration of a maximal recommended activity of 20 MBq for an adult weighing 70 kg is about 0.38 mSv.

For an administered activity of 20 MBq the typical radiation dose to the target organ (stomach) is 0.44 mGy and the typical radiation doses to the critical organs (upper large intestine and lower large intestine) are 2.4 and 1.66 mGy, respectively.

1. 12. INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS

Withdrawals should be performed under aseptic conditions. The vials must not be opened, 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

Add the required amount of Sodium Pertechnetate(^99mTc) Injection (Fission or Non-Fission), up to a maximum 11.1 GBq (300 mCi), in a volume of 2-10 mL to a vial of Technescan DTPA. Mix until the content of the vial is completely dissolved. After 15-30 minutes incubation at 15-25ºC, the preparation is ready for administration to a patient.

Properties of the labelled compound:

Clear to slightly opalescent, colourless aqueous solution. pH : 4.0-5.0

Labelling yield : ≥ 95%

Quality control instructions

Quality control is performed by thin layer chromatography (TLC) using fiberglass sheets coated with silica gel.

1. a)

   Develop 5 to 10 µL in 0.9% m/V solution of sodium chloride R;

   technetium pentetate complex and pertechnetate ion migrate near the solvent front, impurities in colloidal form remain at the start.

2. b) Develop 5 to 10 µL in methyl ethyl ketone R; pertechnetate ion migrates near the solvent front, technetium pentetate complex and impurities in colloidal form remain at the start.

For details, see the European Pharmacopoeia Monograph 642.