Summary of Product Characteristics (SmPC) - Endolucinbeta 40 GBq/ml Radiopharmaceutical Precursor solution
1 NAME OF THE MEDICINAL PRODUCT
EndolucinBeta 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) (as chloride).
The ART is 12:00 pm (noon) on the scheduled day of radiolabelling as indicated by the customer and can be within 0 to 7 days starting from the day of manufacture.
Each 2 mL vial contains an activity ranging from 3 – 80 GBq, corresponding to 0.73 – 19 micrograms of Lutetium (177Lu), at ART. The volume is 0.075 – 2 mL.
The theoretical specific activity is 4,110 GBq/mg of Lutetium (177Lu). The specific activity of the medicinal product at ART is indicated on the label and always greater than 3,000 GBq/mg.
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−2 s−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 6.647 days. The primary radiation emissions of Lutetium (177Lu) are shown in Table 1.
Table 1: Lutetium (177Lu) principle 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
EndolucinBeta 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
EndolucinBeta is only to be used by specialists experienced with in vitro radiolabelling.
Posology
The quantity of EndolucinBeta required for radiolabelling and the quantity of Lutetium (177Lu)-labelled medicinal product that is subsequently administered will depend on the medicinal product 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
EndolucinBeta is intended for in vitro radiolabelling of medicinal products which are subsequently administered by the approved route.
EndolucinBeta 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.
EndolucinBeta 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 haematological 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 (177 Lu) 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 and the radiopharmacist 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 EndolucinBeta 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 exposure 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 EndolucinBeta 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
Female patients of reproductive potential should be advised to use contraception during the treatment with medicines labelled with EndolucinBeta and for 7 months after the last dose. 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.
Men of reproductive potential
Male patients with female partners of reproductive potential should be advised to use barrier method of contraception (e.g., condom) along with another highly effective contraceptive method during the treatment with medicines labelled with EndolucinBeta and for 4 months after the last dose.
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
According to literature reports and taking a conservative approach (maximum patient dose of 10 GBq, average labelling yield and no additional measures), it may be considered that 177Lu-labelled medicinal products do not 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 EndolucinBeta 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).
Tabulated list of adverse reactions
| MedDRA | Very common | Common | Uncommon | Not known | ||
| system | ||||||
| organ class | ||||||
Neoplasms benign, malignant and unspecified (including cysts and polyps) | Refractory cytopenia with multilineage dysplasia (Myelodyspl astic syndrome) (see | Acute myeloid leukaemia (see section 4.4) | ||||
Blood and lymphatic system disorders | Anaemia Thrombo-cytopenia Leukopenia Lymphopeni a | Neutropenia | Pancytopenia | |||
| Endocrine disorders | Carcinoid crisis | |||||
Metabolism and nutrition disorders | Tumour lysis syndrome | |||||
Gastrointest inal disorders | Nausea Vomiting | Dry mouth | ||||
Skin and subcutaneou s 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 EndolucinBeta will lead to increased bone marrow toxicity and haematopoietic stem cell damage. Therefore, in case of an inadvertent administration of EndolucinBeta, 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 EndolucinBeta 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 EndolucinBeta, 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 European Medicines Agency has waived the obligation to submit the results of the studies with EndolucinBeta 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
In the male and female rat, following intravenous administration, Lutetium (177Lu) chloride is rapidly cleared from the blood: at 5 min post injection, only 1.52 % of the injected activity (%ID) is found in blood (corresponding to 0.08 %ID/g) and no activity above background levels remains 1 h post dose. Lutetium (177Lu) chloride distributes mainly to the liver, spleen and bone. After one hour, the amount in the liver is 9.56 % of the injected activity per gram (%ID/g) and in the spleen 5.26 %ID/g. In bone, the content increases from 0.01 %ID/g at 5 min to 0.23 %ID/g after 12 h. For the next 28 days, further uptake of Lutetium (177Lu) can be observed in the bone, which is compensated in part by radioactive decay. Taking into account the radioactive half-life of Lutetium (177Lu) of 6.647 days, the radioactivity remaining in the bone after 28 days is only about 0.06 %ID/g.
Faecal and urinary elimination is slow. As a result of both excretion and radioactive decay, the total radioactivity remaining in the body after 28 days is about 1.8 % of the injected dose.
5.3 Preclinical safety data
The toxicity of non-radioactive Lutetium chloride has been studied in different mammalian species and using different administration routes. The intraperitoneal LD50 in mice was found to be approximately 315 mg/kg. In cats, no pharmacological effects on respiration and cardiovascular function were observed up to a cumulative intravenous dose of 10 mg/kg. A high dose of 10 GBq of Lutetium (177Lu)-chloride contains 2.4 µg Lutetium, corresponding to a human dose of 0.034 µg/kg. This dose is approximately 7 orders of magnitude lower than the intraperitoneal LD50 in mice and more than 5 orders of magnitude lower than the NOEL observed in cats. Therefore, Lutetium metal-ion toxicity of EndolucinBeta-labelled medicinal products can be excluded.
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 9 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 the original package in order to avoid unnecessary radiation exposure.
Storage of radiopharmaceuticals should be in accordance with national regulation on radioactive materials.
This medicinal product does not require any special temperature storage conditions
6.5 Nature and contents of container
Colourless type I glass 2 mL vial with a V-shaped bottom, with a bromobutyl stopper, closed with an aluminium seal.
The vials are placed into a lead container for protective shielding.
Pack size: 1 vial
6.6 Special precautions for disposal
EndolucinBeta 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
ITM Medical Isotopes GmbH
Lichtenbergstrasse 1
85748 Garching/Munich
Germany
8 MARKETING AUTHORISATION NUMBER(S)
2 mL vial: PLGB 45370/0001
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
01/01/2021
10 DATE OF REVISION OF THE TEXT
08/06/2026
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 EndolucinBeta.
The dosimetry estimates were based on a rat biodistribution study performed according to MIRD pamphlet no.16, and the calculations were performed using the OLINDA 1.1 software package. Time points for measurements were 5 minutes, 1 hour, 12 hours, 2 days, 7 days and 28 days.
Table 2: Estimated organ absorbed radiation doses and effective doses
(mSv/MBq) after inadvertent intravenous administration of 177LuCl3 for various human age classes, based on data collected in rats (n = 24)
| Organ | Absorbed dose per unit radioactivity administered (mSv/MBq) Adult (73.7 kg) 15 years old (56.8 kg) 10 years old (33.2 kg) 5 years old (19.8 kg) 1 year old (9.7 kg) | ||||
| Adrenals | 0.2130 | 0.3070 | 0.4450 | 6.0400 | 0.9120 |
| Brain | 0.0056 | 0.0068 | 0.0089 | 1.3500 | 0.0197 |
| Breasts | 0.0107 | 0.0134 | 0.0239 | 0.0377 | 0.0697 |
| Gallbladder wall | 0.1090 | 0.1240 | 0.1610 | 0.2530 | 0.4500 |
| Lower large intestine wall | 0.0104 | 0.0097 | 0.0167 | 0.0292 | 0.0522 |
| Small intestine | 0.1090 | 0.0244 | 0.0434 | 0.0731 | 0.1260 |
| Stomach wall | 0.0556 | 0.0381 | 0.0648 | 0.1040 | 0.1860 |
| Upper large intestine wall | 0.0297 | 0.0334 | 0.0609 | 0.1050 | 0.1830 |
| Heart wall | 0.0415 | 0.0535 | 0.0805 | 0.1190 | 0.2090 |
| Kidneys | 0.3720 | 0.4490 | 0.6460 | 0.956 | 1.7200 |
| Liver | 5.5600 | 7.5600 | 11.900 | 17.900 | 35.700 |
| Lungs | 0.0574 | 0.0808 | 0.1140 | 0.1720 | 0.3230 |
| Muscle | 0.0143 | 0.0180 | 0.0260 | 0.0386 | 0.0697 |
| Ovaries | 0.0106 | 0.0129 | 0.0224 | 0.0379 | 0.0709 |
| Pancreas | 0.0663 | 0.0818 | 0.1250 | 0.1900 | 0.3050 |
| Organ | Absorbed dose per unit radioactivity administered (mSv/MBq) Adult (73.7 kg) 15 years old (56.8 kg) 10 years old (33.2 kg) 5 years old (19.8 kg) 1 year old (9.7 kg) | ||||
| Red marrow | 0.5910 | 0.6670 | 1.2300 | 2.6200 | 6.6000 |
| Osteogenic cells | 2.1500 | 2.8100 | 4.5900 | 7.8000 | 18.800 |
| Skin | 0.0073 | 0.0091 | 0.0140 | 0.0217 | 0.0412 |
| Spleen | 5.7300 | 8.5000 | 13.500 | 21.600 | 40.700 |
| Testes | 0.0022 | 0.0029 | 0.0049 | 0.0088 | 0.0188 |
| Thymus | 0.0102 | 0.0128 | 0.0179 | 0.0276 | 0.0469 |
| Thyroid | 0.0058 | 0.0075 | 0.0113 | 0.0206 | 0.0377 |
| Urinary bladder wall | 0.0043 | 0.0056 | 0.0116 | 0.0247 | 0.0435 |
| Uterus | 0.0085 | 0.0102 | 0.0184 | 0.0331 | 0.0635 |
| Rest of body | 0.2330 | 0.2990 | 0.5060 | 0.8380 | 1.6900 |
Effective dose (mSv/MBq) | 0.534 | 0.721 | 1.160 | 1.88 | 3.88 |
The effective dose to a 73.7 kg adult resulting from an inadvertently injected intravenous activity of 1 GBq would be 534 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. 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 EndolucinBeta 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.