Summary of Product Characteristics (SmPC) - Monlutenca 40 GBq/ml Radiopharmaceutical Precursor, solution
1 NAME OF THE MEDICINAL PRODUCT
Monlutenca 40 GBq/ml radiopharmaceutical precursor, solution
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml of solution contains 40 GBq lutetium (177Lu) chloride on activity reference time (ART), corresponding to 10 micrograms of lutetium (177Lu). The minimal specific activity is 3000 GBq/mg lutetium (177Lu) at ART.
Each 3 ml vial contains an activity from 1 to 120 GBq, corresponding to 0.25-30 micrograms of lutetium (177Lu), at ART. The volume is 0.025-3 ml.
Each 10 ml vial contains an activity from 1 to 200 GBq, corresponding to 0.25-50 micrograms of lutetium (177Lu), at ART. The volume is 0.025-5 ml.
Each 20 ml vial contains an activity from 1 to 600 GBq, corresponding to 0.25-150 micrograms of lutetium (177Lu), at ART. The volume is 0.025-15 ml.
Non carrier added (n.c.a.) lutetium (177Lu) chloride is produced by the irradiation of highly enriched (> 99 %) ytterbium (176Yb) in neutron sources with a thermal neutron flux between 1013 and 1016 cm-2s-1. The following nuclear reaction is ongoing in the irradiation:
176Yb(n, γ)177Yb → 177Lu
The produced ytterbium (177Yb) with a half-life of 1.9 h decays to lutetium (177Lu). In a chromatographic process, the accumulated lutetium (177Lu) is separated chemically from the original target material.
lutetium (177Lu) emits both medium-energy beta particles and imageable gamma photons and has a half-life of 6.6 days. The primary radiation emissions of lutetium (177Lu) are shown in Table 1.
Table 1: Lutetium (177Lu) principal radiation emission data
Radiation Energy (keV)* Abundance (%) Beta (β−) 47.66 11.61
Beta (β−) 111.69 9.0
Beta (β−) 149.35 79.4 Gamma 112.9498 6.17
Gamma 208.3662 10.36
* Mean energies are listed for beta particles
Lutetium (177Lu) decays by emission of beta radiation to stable hafnium (177Hf). For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Radiopharmaceutical precursor, solution.
Clear colourless solution.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Monlutenca is a radiopharmaceutical precursor, and it is not intended for direct use in patients. It is to be used only for the radiolabelling of carrier molecules that have been specifically developed and authorised for radiolabelling with lutetium (177Lu) chloride.
4.2 Posology and method of administration
Monlutenca is only to be used by specialists experienced with in vitro radiolabelling.
Posology
The quantity of Monlutenca required for radiolabelling and the quantity of lutetium (177Lu)-labelled medicinal product that is subsequently administered will depend on the medicinal product to be radiolabelled and its intended use. Refer to the Summary of Product Characteristics/Package Leaflet of the particular medicinal product to be radiolabelled.
Paediatric population
For more information concerning paediatric use of lutetium (177Lu)-labelled medicinal products refer to the Summary of Product Characteristics/Package Leaflet of the medicinal product to be radiolabelled.
Method of administration
Monlutenca is intended for in vitro radiolabelling of medicinal products which are subsequently administered by the approved route.
Monlutenca should not be administered directly to the patient.
For instructions on preparation of the medicinal product before administration, see section 12.
4.3 Contraindications
- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
- Established or suspected pregnancy or when pregnancy has not been excluded (see section 4.6).
4.4 Special warnings and precautions for use
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 therapeutic effect.
Monlutenca is not to be administered directly to the patient, but must be used for the radiolabelling of carrier molecules, such as monoclonal antibodies, peptides, vitamins or other substrates.
Renal impairment and hematological disorders
Careful consideration of the benefit risk ratio in these patients is required since an increased radiation exposure is possible. It is recommended to perform individual radiation dosimetry assessments of specific organs, which may not be the target organ of therapy.
Myelodysplastic syndrome and acute myeloid leukaemia
Myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) have been observed after treatment with lutetium (177Lu) peptide receptor radionuclide therapy for neuroendocrine tumours (see section 4.8). This should be taken into account when considering the benefit/risk, especially in patients with possible risk factors like prior exposure to chemotherapeutic agents (such as alkylating agents).
Myelosuppression
Anaemia, thrombocytopenia, leucopenia, lymphopenia, and less commonly neutropenia may occur during radioligand therapy with lutetium (177Lu). Most events are mild and transient, but in some cases patients have required blood and platelet transfusions. In some patients more than one cell line may be affected and pancytopenia requiring treatment discontinuation has been described. A blood count should be taken at baseline and monitored regularly during treatment, in accordance with clinical guidance.
Renal irradiation
Radiolabelled somatostatin analogues are excreted by the kidney. Radiation nephropathy has been reported following peptide receptor radionuclide therapy for neuroendocrine tumours using other radioisotopes. Renal function including glomerular filtration rate (GFR) should be assessed at baseline and during treatment and renal protection should be considered, in accordance with clinical guidance of the radiolabelled medicinal product.
Hepatotoxicity
Cases of hepatotoxicity have been reported in the post-marketing setting and in the literature in patients with liver metastases undergoing treatment with lutetium (177Lu) peptide receptor radionuclide therapy for neuroendocrine tumours. Liver function should be monitored regularly during treatment. Dose reduction may be necessary in affected patients.
Hormone release syndromes
There have been reports of carcinoid crisis and other syndromes associated with release of hormones from functional neuroendocrine tumours following lutetium (177Lu) peptide receptor radionuclide therapy, which may be related to irradiation of tumour cells. Reported symptoms include flushing and diarrhoea associated with hypotension. Observation of patients by overnight hospitalisation should be considered in some cases (e.g., patients with poor pharmacologic control of symptoms). In case of hormonal crises, treatments may include intravenous high dose somatostatin analogues, intravenous fluids, corticosteroids, and correction of electrolyte disturbances in patients with diarrhoea and/or vomiting.
Tumour lysis syndrome
Tumour lysis syndrome has been reported following lutetium (177Lu) radioligand therapy. Patients with a history of renal insufficiency and high tumour burden may be at greater risk and should be treated with increased caution. Renal function as well as electrolyte balance should be assessed at baseline and during treatment.
Extravasation
There have been reports of extravasation of lutetium (177Lu)-labelled ligands in the post-marketing setting. In case of extravasation, infusion of the medicinal product should be immediately ceased, and the nuclear medicine physician should be promptly informed. Management should be in accordance with local protocols.
Radiation protection
Point-source approximation shows that the average dose rate experienced 20 hours after administration of a dose of 7.3 GBq Monlutenca labelled radiopharmaceutical (residual radioactivity 1.5 GBq) by a person at 1 meter distance from the patient’s body centre with an abdominal radius of 15 cm is 3.5 µSv/h. Doubling the distance to the patient to 2 meters reduces the dose rate by a factor of 4 to 0.9 µSv/h. The same dose in a patient with an abdominal radius of 25 cm yields a dose rate at 1 meter of 2.6 µSv/h. The generally accepted threshold for discharge of the treated patient from the hospital is 20 µSv/h. In most countries, the dose limit for hospital staff is set the same as for the general public at 1 mSv/year. When taking the 3.5 µSv/h dose rate as an average, this would allow hospital staff to work approx. 300 hours/year in close vicinity of patients treated with Monlutenca labelled radiopharmaceuticals without wearing radiation protection. Of course, the nuclear medicine staff is expected to wear standard radiation protection. Any other person in close vicinity of the treated patient should be informed about possibilities to reduce his/her exposure due to radiation emitted from the patient
Specific warnings
For information concerning special warnings and special precautions for use of lutetium (177Lu)- labelled medicinal products refer also to the Summary of Product Characteristics/Package Leaflet of the medicinal product to be radiolabelled.
Further precautions with respect to relatives, carers and hospital staff are provided in section 6.6.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies of lutetium (177Lu) chloride with other medicinal products have been performed.
For information concerning interactions associated with the use of lutetium (177Lu)-labelled medicinal products refer to the Summary of Product Characteristics/Package Leaflet of the medicinal product to be radiolabelled.
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. Before the use of 177Lu labelled medicinal products, pregnancy should be excluded using an adequate/validated test.
Pregnancy
The use of lutetium (177Lu)-labelled medicinal products is contraindicated during established or suspected pregnancy or when pregnancy has not been excluded due to the risk of ionizing radiation to the foetus (see section 4.3).
Breast-feeding
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, and the expressed feeds discarded.
Fertility
Effects of lutetium (177Lu) chloride on male and female fertility have not been studied in animals. Low exposures could be demonstrated for male and female sexual organs. It cannot be excluded that 177Lu-labelled medicinal products lead to reproductive toxicity including spermatogenetic damage in male testes or genetic damage in male testes or female ovaries.
Further information concerning the use of lutetium (177Lu)-labelled medicinal products concerning fertility is specified in the Summary of Product Characteristics/Package Leaflet of the medicinal product to be radiolabelled.
4.7 Effects on ability to drive and use machines
Effects on ability to drive and to use machines following treatment by lutetium (177Lu)-labelled medicinal products will be specified in the Summary of Product Characteristics/Package Leaflet of the medicinal product to be radiolabelled.
4.8 Undesirable effects
Summary of the safety profile
Adverse reactions following the administration of a lutetium (177Lu)-labelled medicinal product prepared by radiolabelling with Monlutenca will be dependent on the specific medicinal product being used. Such information will be supplied in the Summary of Product Characteristics/Package Leaflet of the medicinal product to be radiolabelled.
Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. The radiation dose resulting from therapeutic exposure may result in higher incidence of cancer and mutations. In all cases, it is necessary to ensure that the risks of the radiation are less than from the disease itself.
Adverse reactions are divided into groups according to the MedDRA convention frequencies: 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).
Table 2: Tabulated list of adverse reactions
| MedDRA system organ | Very common | Common | Uncommon | Not known | ||
| class | ||||||
Neoplasms benign, malignant and unspecified (including cysts and polyps) | Refractory cytopenia with multilineage dysplasia (Myelodysplastic syndrome) (see | Acute myeloid leukaemia (see section 4.4) | ||||
| Blood and lymphatic system disorders | Anaemia Thrombo- cytopenia Leukopenia Lymphopenia | Neutropenia | Pancytopenia | |||
| Endocrine disorders | Carcinoid crisis | |||||
| Metabolism and nutrition disorders | Tumour lysis syndrome | |||||
| Gastrointestinal disorders | Nausea Vomiting | Dry mouth | ||||
| Skin and subcutaneous tissue disorders | Alopecia | |||||
Description of selected adverse reactions
Dry mouth has been reported among patients with metastatic castration resistant prostate cancer receiving PSMA-targeted lutetium (177Lu)-labelled radioligands and has been transient.
Skin and subcutaneous tissue disorders: Alopecia, described as mild and temporary, has been observed among patients receiving lutetium (177Lu) peptide receptor radionuclide therapy for neuroendocrine tumours.
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, Website:www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
The presence of free lutetium (177Lu) chloride in the body after an inadvertent administration of Monlutenca will lead to increased bone marrow toxicity and haematopoietic stem cell damage. Therefore, in case of an inadvertent administration of Monlutenca, the radiotoxicity for the patient must be reduced by immediate (i.e. within 1 hour) administration of preparations containing chelators like Ca-DTPA or Ca-EDTA in order to increase the elimination of the radionuclide from the body.
The following preparations must be available in medical institutions, which use Monlutenca for labelling of carrier molecules for therapeutic purposes:
- Ca-DTPA (trisodium calcium diethylenetriaminepentaacetate) or
- Ca-EDTA (calcium disodium ethylenediaminetetraacetate)
These chelating agents help with the elimination of lutetium (177Lu) radiotoxicity by an exchange between the calcium ion in the complex and the lutetium (177Lu) ion. Due to the capacity of the chelating ligands (DTPA, EDTA) of forming water soluble complexes, the complexes and bound lutetium (177Lu) are rapidly eliminated by the kidneys.
One gram of the chelating agents should be administered by slow intravenous injection over 3-4 minutes or by infusion (1 g in 100 – 250 ml of glucose, or sodium chloride 9 mg/ml (0.9 %) solution for injection).
The chelating efficacy is greatest immediately or within one hour of exposure when the radionuclide is circulating in or available to tissue fluids and plasma. However, a post-exposure interval > 1 hour does not preclude the administration and effective action of chelator with reduced efficiency. Intravenous administration should not be protracted over more than 2 hours.
In any case, the blood parameters of the patient have to be monitored and the appropriate actions immediately taken if there is evidence of radiotoxicity.
The toxicity of free lutetium (177Lu) due to in-vivo release from the labelled biomolecule in the body during therapy could be reduced by post-administration of chelating agents.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other therapeutic radiopharmaceuticals, ATC code: V10X
The pharmacodynamic properties of lutetium (177Lu)-labelled medicinal products prepared by radiolabelling with Monlutenca, prior to administration, will be dependent on the nature of the medicinal product to be radiolabelled. Refer to the Summary of Product Characteristics/Package Leaflet of the particular medicinal product to be radiolabelled.
Lutetium (177Lu) emits β
-particles of moderate maximum energy (0.498 MeV) with a maximum tissue penetration of approximately 2 mm. Lutetium (177Lu) also emits low-energy γ
-rays which allow scintigraphic, biodistribution and dosimetry studies with the same lutetium (177Lu)-labelled medicinal products.
Paediatric population
The MHRA has waived the obligation to submit the results of the studies with 177Lu in all subsets of the paediatric population on grounds that the specific medicinal product does not represent a significant therapeutic benefit over existing treatments for paediatric patients. This waiver does however not extend to any therapeutic uses of the medicinal product when linked to a carrier molecule (see section 4.2 for information on paediatric use).
5.2 Pharmacokinetic properties
Distribution after inadvertent intravenous administration of lutetium (177Lu) chloride
Based on preclinical studies, Lu-177 appears to be rapidly cleared from the blood and excreted by the kidneys, and its gastrointestinal absorption is low. In most preclinical studies, radioactivity administered by parenteral routes is largely absorbed by bone tissue and remains there for a long time, with half-life of several months to years. Distribution to liver and spleen can be substantial as well but is usually less than to the bone. This pharmacokinetic pattern does, however, not apply to Lu-177 when chelated in stable fashion, where pharmacokinetics is determined by the carrier and usually it is excreted by kidneys and bone and reticuloendothelial involvement is minimal.
Due to its poor solubility at physiological pH, Lu-177 forms colloidal or hydroxide complexes, which may interfere with clearance.
5.3 Preclinical safety data
Single dose studies with non-radioactive lutetium chloride in animals have shown LD50 values in the range of 12.5 mg/kg when given intravenously to cats to 4.4 g/kg when given orally to rats. A high dose of 10 GBq of lutetium (177Lu)-chloride contains 2.4 µg lutetium. Therefore lutetium metal- ion toxicity of Monlutenca-labelled medicinal products can be excluded. 177Lutetium dose-dependently increased the frequency of osteosarcomas in mice.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Hydrochloric acid, diluted
6.2 Incompatibilities
Radiolabelling of medicinal products, such as monoclonal antibodies, peptides, vitamins or other substrates, with lutetium (177Lu) chloride is very sensitive to the presence of trace metal impurities.
It is important that all glassware, syringe needles etc., used for the preparation of the radiolabelled medicinal product are thoroughly cleaned to ensure freedom from such trace metal impurities. Only syringe needles (for example, non-metallic) with proven resistance to dilute acid should be used to minimise trace metal impurity levels.
In the absence of compatibility studies, this medicinal product must not be mixed with medicinal products other than the medicinal products to be radiolabelled.
6.3 Shelf life
Up to 15 days from the date of manufacture.
From a microbiological point of view, unless the method of withdrawal from the vial or any insertion into the vial preclude the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.
6.4 Special precautions for storage
Store in its original lead shield.
Store in the original package in order to avoid unnecessary radiation exposure.
Storage of radiopharmaceuticals should be in accordance with national regulation on radioactive materials.
6.5 Nature and contents of container
Primary package:
- Colourless glass 3 ml and 10 ml vials closed with bromobutyl stoppers and aluminum overseals.
- Colourless glass 3 ml, 10 ml, 20 ml vials closed with fluoropolymer coated bromobutyl stoppers and aluminum overseals.
The volume filled in the vials can vary in the ranges of 0.025-3 ml, 0.025-5 ml and 0.025-15 ml, respectively.
Secondary package: Lead shield
6.6 Special precautions for disposal
Monlutenca is not intended for direct use in patients.
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.
For instructions on extemporary preparation of the medicinal product before administration, see section 12.
If at any time in the preparation of this medicinal product the integrity of this container 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 surface dose rates and the accumulated dose depend on many factors. Measurements on the location and during work are critical and should be practiced for more precise and instructive determination of overall radiation dose to the staff. Healthcare personnel are advised to limit the time of close contact with patients injected with lutetium (177Lu)-labelled radiopharmaceuticals. The use of television monitor systems to monitor the patients is recommended. Given the long half-life of lutetium (177Lu), it is specially recommended to avoid internal contamination. For this reason it is mandatory to use protective high quality (latex/nitrile) gloves in any direct contact with the radiopharmaceutical (vial/syringe) and with the patient. For minimising radiation exposure resulting from repeated exposition there is no recommendation except the strict observance of the above ones.
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.
Any unused medicinal product or waste material must be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Curium Romania SRL
Pantelimon, Str. Gradinarilor, nr.1
Ilfov
Romania
8 MARKETING AUTHORISATION NUMBER(S)
PL 5642/0002
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
Date of first authorisation: 21/05/2024
Date of latest renewal:
10 DATE OF REVISION OF THE TEXT
31/10/2025
11 DOSIMETRY
The radiation dose received by various organs following intravenous administration of a lutetium (177Lu)-labelled medicinal product is dependent on the specific molecule being radiolabelled.
Information on radiation dosimetry of each different medicinal product following administration of the radiolabelled preparation is available in the Summary of Product Characteristics/Package Leaflet of the particular medicinal product to be radiolabelled.
The dosimetry table below is presented in order to evaluate the contribution of non-conjugated lutetium (177Lu) to the radiation dose following the administration of a lutetium (177Lu)-labelled medicinal product or resulting from an accidental intravenous injection of Monlutenca.
Dose calculations (absorbed normalised doses for target organs [mGy/MBq] and effective normalised doses [mSv/MBq]) were performed in IDAC Dose 2.1 dose calculator using the mean  value (mean between the  values obtained from each considered animal study) for each source organ. Organ doses are listed below for an adult male and female model as well as for 15-year, 12-year 10-year, 5-year, 1-year and newborn male and female models, according to ICRP 89 (International Commission on Radiological Protection).
The results show liver, kidneys, lungs and heart wall in children as the significant target organs for the biodistribution of lutetium (177Lu) chloride.
Table 3: Estimated organ normalised absorbed doses [mGy/MBq] and normalised effective dose [mSv/MBq] in male models as calculated with the IDAC Dose 2.1 dose calculator of 177LuCl3 *
| Organ | Adult | 15 years | 12 years | 10 years | 5 years | 1 year | Newbor | ||||||||||||||
| (mGy/ | (mGy/ | (mGy/ | (mGy/ | (mGy/ | (mGy/ | n (mGy/ | |||||||||||||||
| MBq) | MBq) | MBq) | MBq) | MBq) | MBq) | MBq) | |||||||||||||||
| Adipose tissue | 0.123 | 0.00608 | 0.00632 | 0.00583 | 0.00675 | 0.00840 | 0.00817 | ||||||||||||||
| Adrenals | 0.191 | 0.0634 | 0.0691 | 0.0628 | 0.0773 | 0.0976 | 0.0949 | ||||||||||||||
Alveolar- interstitial tissue | 0.508 | 0.442 | 0.490 | 0.400 | 0.340 | 0.525 | 0.464 | ||||||||||||||
| Brain | 0.0518 | 0.0869 | 0.106 | 0.0650 | 0.167 | 0.241 | 0.264 | ||||||||||||||
| Breast | 0.0119 | 0.0126 | 0.0127 | 0.0119 | 0.0134 | 0.0164 | 0.0160 | ||||||||||||||
| Bronchi (bound) | 0.0511 | 0.0605 | 0.0641 | 0.0565 | 0.0542 | 0.0724 | 0.0689 | ||||||||||||||
Bronchi (sequestered) | 0.0511 | 0.0605 | 0.0641 | 0.0565 | 0.0542 | 0.0724 | 0.0689 | ||||||||||||||
| Bronchioles | 0.0502 | 0.442 | 0.490 | 0.400 | 0.540 | 0.525 | 0.464 | ||||||||||||||
| Colon wall | 0.0184 | 0.0117 | 0.0121 | 0.0112 | 0.0136 | 0.0171 | 0.0163 | ||||||||||||||
| Endosternum (surface) | 0.00615 | 0.00486 | 0.00506 | 0.00455 | 0.00557 | 0.00707 | 0.00696 | ||||||||||||||
| ET region | 0.00607 | 0.00220 | 0.00248 | 0.00189 | 0.00319 | 0.00435 | 0.00462 | ||||||||||||||
| ET1 basal cells | 0.00468 | 0.000238 | 0.00109 | 0.000852 | 0.00139 | 0.00189 | 0.00198 | ||||||||||||||
| ET2 basal cells | 0.00607 | 0.00220 | 0.00248 | 0.00190 | 0.00319 | 0.00435 | 0.00462 | ||||||||||||||
| Eye lens | 0.00317 | 0.000915 | 0.00107 | 0.000743 | 0.00150 | 0.00211 | 0.00228 | ||||||||||||||
| Gallbladder wall | 0.102 | 0.118 | 0.117 | 0.108 | 0.134 | 0.170 | 0.159 | ||||||||||||||
| Heart wall | 0.0243 | 3.21 | 3.17 | 3.18 | 3.29 | 3.49 | 3.90 | ||||||||||||||
| Kidneys | 1.37 | 1.33 | 1.61 | 1.43 | 1.80 | 2.27 | 2.33 | ||||||||||||||
| Left colon wall | 0.0166 | 0.0102 | 0.0107 | 0.00994 | 0.0118 | 0.0147 | 0.0141 | ||||||||||||||
| Liver | 1.05 | 1.25 | 1.24 | 1.15 | 1.42 | 1.82 | 1.68 | ||||||||||||||
| Lung | 0.354 | 0.315 | 0.348 | 0.286 | 0.245 | 0.374 | 0.332 | ||||||||||||||
| Lymphatic nodes | 0.0178 | 0.0233 | 0.0236 | 0.0225 | 0.0244 | 0.0287 | 0.0293 | ||||||||||||||
| Lymphatic nodes (ET region) | 0.00569 | 0.00254 | 0.00263 | 0.00236 | 0.00272 | 0.00344 | 0.00346 | ||||||||||||||
| Lymphatic nodes (Th region) | 0.0193 | 0.0439 | 0.0444 | 0.0426 | 0.0437 | 0.0503 | 0.0528 | ||||||||||||||
| Muscle | 0.00566 | 0.00372 | 0.00386 | 0.00354 | 0.00410 | 0.00515 | 0.00497 | ||||||||||||||
| Esophagus | 0.0217 | 0.0458 | 0.0489 | 0.0443 | 0.0475 | 0.0548 | 0.0568 | ||||||||||||||
| Oral mucosa | 0.00296 | 0.00148 | 0.00161 | 0.00130 | 0.00194 | 0.00259 | 0.00270 | ||||||||||||||
| Ovaries | NA | NA | NA | NA | NA | NA | NA | ||||||||||||||
| Pancreas | 0.160 | 0.0385 | 0.393 | 0.0363 | 0.0441 | 0.0556 | 0.0528 | ||||||||||||||
| Pituitary gland | 0.00743 | 0.00670 | 0.00814 | 0.00507 | 0.0126 | 0.0181 | 0.0198 | ||||||||||||||
| Prostate | 0.00609 | 0.000281 | 0.000296 | 0.000271 | 0.000331 | 0.000419 | 0.000402 | ||||||||||||||
| Recto-sigmoid colon wall | 0.00964 | 0.000649 | 0.000690 | 0.000631 | 0.000770 | 0.000971 | 0.000938 | ||||||||||||||
| Red bone marrow | 0.0122 | 0.0106 | 0.0110 | 0.0101 | 0.0117 | 0.0146 | 0.0142 | ||||||||||||||
| Right colon wall | 0.0245 | 0.0197 | 0.0193 | 0.0177 | 0.0218 | 0.0277 | 0.0262 | ||||||||||||||
| Salivary glands | 0.00331 | 0.00147 | 0.00159 | 0.00131 | 0.00187 | 0.00249 | 0.00259 | ||||||||||||||
| Skin | 0.00761 | 0.00236 | 0.00243 | 0.00223 | 0.00263 | 0.00331 | 0.00320 | ||||||||||||||
| Small intestine wall | 0.0173 | 0.00916 | 0.00966 | 0.00887 | 0.0108 | 0.0135 | 0.0130 |
| Spleen | 0.402 | 0.407 | 0.367 | 0.385 | 0.467 | 0.539 | 0.330 |
| Stomach wall | 0.0289 | 0.0358 | 0.0360 | 0.0340 | 0.0362 | 0.0475 | 0.0464 |
| Testes | 0.00507 | 0.000045 1 | 0.000047 6 | 0.000043 5 | 0.000053 1 | 0.000067 1 | 0.000064 5 |
| Thymus | 0.0116 | 0.0200 | 0.0204 | 0.0192 | 0.0197 | 0.0234 | 0.0240 |
| Thyroid | 0.00953 | 0.00695 | 0.00715 | 0.00660 | 0.00687 | 0.00846 | 0.00844 |
| Tongue | 0.00273 | 0.00158 | 0.00170 | 0.001.40 | 0.00202 | 0.00268 | 0.00278 |
| Tonsils | 0.00466 | 0.00185 | 0.00216 | 0.00149 | 0.00306 | 0.00430 | 0.00465 |
| Ureters | 0.0177 | 0.00961 | 0.0105 | 0.00954 | 0.0117 | 0.0148 | 0.0145 |
| Urinary bladder wall | 0.00711 | 0.000574 | 0.000606 | 0.000555 | 0.000678 | 0.000856 | 0.000824 |
| Uterus/cervix | NA | NA | NA | NA | NA | NA | NA |
| Effective dose ICRP 60 (mSv/MBq) | 0.141 | 0.192 | 0.194 | 0.182 | 0.195 | 0.238 | 0.263 |
| Effective dose ICRP 103 (mSv/MBq) | 0.131 | 0.168 | 0.175 | 0.159 | 0.175 | 0.223 | 0.214 |
*For calculation of the dosimetry data, please refer to Schmitt A, Bernhardt P, Nilsson O, Ahlman H, Kölby L, Schmitt J, Forssel-Aronsson E. Biodistribution and dosimetry of 177Lu-labeled [DOTA0,Tyr3]octreotate in male nude mice with human small cell lung cancer. Cancer Biother Radiopharm. Aug 2003; 18(4):593-599.
Table 4. Estimated organ normalised absorbed doses [mGy/MBq] and normalised effective dose [mSv/MBq] in female models as calculated with the IDAC Dose 2.1 dose calculator of 177LuCl3 *
| Organ | Adult (mGy/ MBq) | 15 years | 12 years | 10 years (mGy/ MBq) | 5 years | 1 year | Newborn | ||||||||||||
| (mGy/ | (mGy/ | (mGy/ | (mGy/ | (mGy/ | |||||||||||||||
| MBq) | MBq) | MBq) | MBq) | MBq) | |||||||||||||||
| Adipose tissue | 0.100 | 0.00460 | 0.00477 | 0.000439 | 0.00509 | 0.00637 | 0.00616 | ||||||||||||
| Adrenals | 0.219 | 0.0803 | 0.0843 | 0.0771 | 0.0948 | 0.120 | 0.115 | ||||||||||||
Alveolar- interstitial tissue | 0.604 | 0.563 | 0.624 | 0.510 | 0.434 | 0.669 | 0.591 | ||||||||||||
| Brain | 0.0580 | 0.0976 | 0.120 | 0.0730 | 0.0187 | 0.270 | 0.296 | ||||||||||||
| Breast | 0.00956 | 0.0158 | 0.0160 | 0.0151 | 0.0164 | 0.0198 | 0.0197 | ||||||||||||
| Bronchi (bound) | 0.0555 | 0.0965 | 0.100 | 0.0919 | 0.0900 | 0.112 | 0.112 | ||||||||||||
Bronchi (sequestered) | 0.0555 | 0.0965 | 0.100 | 0.0919 | 0.0900 | 0.112 | 0.112 | ||||||||||||
| Bronchioles | 0.633 | 0.563 | 0.642 | 0.510 | 0.434 | 0.669 | 0.591 | ||||||||||||
| Colon wall | 0.0128 | 0.00572 | 0.00615 | 0.00560 | 0.00691 | 0.00876 | 0.00848 | ||||||||||||
| Endosternum (surface) | 0.00819 | 0.00696 | 0.00723 | 0.00652 | 0.00785 | 0.00996 | 0.00977 | ||||||||||||
| ET region | 0.00665 | 0.00251 | 0.00274 | 0.00221 | 0.00329 | 0.00440 | 0.00462 | ||||||||||||
| ET1 basal cells | 0.00820 | 0.00149 | 0.00162 | 0.00131 | 0.00199 | 0.00265 | 0.00278 |
| ET2 basal cells | 0.00664 | 0.00251 | 0.00274 | 0.00221 | 0.00329 | 0.00440 | 0.00462 |
| Eye lens | 0.00268 | 0.00151 | 0.00168 | 0.00129 | 0.00219 | 0.00297 | 0.00316 |
| Gallbladder wall | 0.125 | 0.145 | 0.146 | 0.134 | 0.166 | 0.212 | 0.00198 |
| Heart wall | 0.0311 | 4.24 | 4.19 | 4.21 | 4.35 | 4.62 | 5.16 |
| Kidneys | 1.62 | 1.57 | 1.91 | 1.69 | 2.13 | 2.69 | 2.75 |
| Left colon wall | 0.0108 | 0.00373 | 0.00400 | 0.00366 | 0.00448 | 0.00564 | 0.00546 |
| Liver | 1.36 | 1.63 | 1.61 | 1.49 | 1.85 | 2.36 | 2.18 |
| Lung | 0.443 | 0.408 | 0.00449 | 0.371 | 0.319 | 0.483 | 0.432 |
| Lymphatic nodes | 0.0215 | 0.0252 | 0.0260 | 0.0244 | 0.0269 | 0.0322 | 0.0326 |
Lymphatic nodes (ET region) | 0.00505 | 0.00288 | 0.00302 | 0.00267 | 0.00315 | 0.00402 | 0.00409 |
Lymphatic nodes (Th region) | 0.0225 | 0.0505 | 0.0514 | 0.00487 | 0.0493 | 0.0579 | 0.0600 |
| Muscle | 0.00710 | 0.00499 | 0.00518 | 0.00475 | 0.00550 | 0.00691 | 0.00667 |
| Esophagus | 0.0240 | 0.0604 | 0.0604 | 0.0584 | 0.00623 | 0.0715 | 0.0744 |
| Oral mucosa | 0.00390 | 0.00230 | 0.00245 | 0.00209 | 0.00276 | 0.00359 | 0.00371 |
| Ovaries | 0.00863 | 0.000564 | 0.000602 | 0.000549 | 0.000674 | 0.000853 | 0.000822 |
| Pancreas | 0.187 | 0.0408 | 0.0427 | 0.0392 | 0.0481 | 0.0609 | 0.0583 |
| Pituitary gland | 0.00658 | 0.00733 | 0.00885 | 0.00561 | 0.0135 | 0.0193 | 0.0212 |
| Prostate | NA | NA | NA | NA | NA | NA | NA |
| Recto-sigmoid colon wall | 0.00919 | 0.000627 | 0.000669 | 0.000611 | 0.000749 | 0.000947 | 0.000914 |
| Red bone marrow | 0.0164 | 0.0154 | 0.0159 | 0.0146 | 0.0168 | 0.0211 | 0.0204 |
| Right colon wall | 0.0165 | 0.0103 | 0.0110 | 0.0100 | 0.0124 | 0.0158 | 0.0153 |
| Salivary glands | 0.00402 | 0.00213 | 0.00230 | 0.00190 | 0.00269 | 0.00357 | 0.00372 |
| Skin | 0.00890 | 0.00307 | 0.00315 | 0.00289 | 0.00339 | 0.00425 | 0.00411 |
| Small intestine wall | 0.0193 | 0.0125 | 0.0132 | 0.0112 | 0.0149 | 0.0188 | 0.0181 |
| Spleen | 0.490 | 0.496 | 0.448 | 0.470 | 0.570 | 0.659 | 0.405 |
| Stomach wall | 0.0390 | 0.0444 | 0.0449 | 0.0420 | 0.0499 | 0.618 | 0.0585 |
| Testes | NA | NA | NA | NA | NA | NA | NA |
| Thymus | 0.0140 | 0.0297 | 0.0302 | 0.0286 | 0.0292 | 0.0343 | 0.0355 |
| Thyroid | 0.00900 | 0.00744 | 0.00757 | 0.00705 | 0.00735 | 0.00910 | 0.00909 |
| Tongue | 0.00346 | 0.00239 | 0.00254 | 0.00216 | 0.00287 | 0.00373 | 0.00386 |
| Tonsils | 0.00488 | 0.00209 | 0.00229 | 0.00182 | 0.00279 | 0.00375 | 0.00393 |
| Ureters | 0.0204 | 0.0147 | 0.0162 | 0.0146 | 0.0181 | 0.0229 | 0.0225 |
| Urinary bladder wall | 0.00510 | 0.000549 | 0.000584 | 0.000534 | 0.000654 | 0.000527 | 0.000797 |
| Uterus/cervix | 0.00499 | 0.000554 | 0.000591 | 0.000539 | 0.000662 | 0.000837 | 0.000807 |
| Effective dose ICRP 60** (mSv/MBq) | 0.175 | 0.250 | 0.253 | 0.237 | 0.254 | 0.310 | 0.308 |
*For calculation of the dosimetry data, please refer to Schmitt A, Bernhardt P, Nilsson O, Ahlman H, Kölby L, Schmitt J, Forssel-Aronsson E. Biodistribution and dosimetry of 177Lu-labeled [DOTA0,Tyr3]octreotate in male nude mice with human small cell lung cancer. Cancer Biother Radiopharm. Aug 2003; 18(4):593-599.
**IDAC Dose 2.1 only calculates the effective dose according to the ICRP 103 publication for male phantoms
The effective dose to a 70 kg adult male resulting from an inadvertently injected intravenous activity of 1 GBq would be 131 mSv.
12 INSTRUCTIONS FOR PREPARATION OF
RADIOPHARMACEUTICALS
Before use, packaging and radioactivity should be checked. Activity may be measured using an ionisation chamber.
Lutetium (177Lu) is a beta(-)/gamma emitter. Activity measurements using an ionization chamber are very sensitive to geometric factors and therefore should be performed only under geometric conditions which have been appropriately validated.
Usual precautions regarding sterility and radioactivity should be respected.
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 medicinal product should not be used.
The complexing agent and other reagents should be added to the vial with lutetium (177Lu) chloride or a separate reaction vial can be used according to the labelling method. Free lutetium (177Lu) is taken up and accumulates in the bones. This could potentially result in osteosarcomas. It is recommended to add a binding agent such as DTPA prior to intravenous administration of lutetium (177Lu)-labelled conjugates in order to form a complex with free lutetium (177Lu), if present, leading to a rapid renal clearance of lutetium (177Lu).
Adequate quality control of the radiochemical purity of ready to use radiopharmaceuticals gained after radiolabelling with Monlutenca should be assured. Limits for radiochemical impurities should be set recognising the radiotoxicological potential of lutetium (177Lu). Free non-bound lutetium (177Lu) should be consequently minimised.
The optimum labelling pH should be in the range of 5 to 6. Adjusting the pH for labelling should be considered.