Source: European Medicines Agency (EU) Revision Year: 2021 Publisher: Eckert & Ziegler Radiopharma GmbH, Robert-Rössle-Str. 10, D-13125 Berlin, Germany
To be used only for the radiolabelling of carrier molecules, which have been specifically developed and authorised for radiolabelling with this radionuclide.
Radiopharmaceutical precursor – Not intended for direct use in patients.
Yttriga is only to be used by specialists experienced with in vitro radiolabelling.
The quantity of Yttriga required for radiolabelling and the quantity of Yttrium (90Y)-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.
Yttriga is intended for in vitro labelling of medicinal products which are subsequently administered by the approved route.
The radiation dose received by the various organs following intravenous administration of an Yttrium (90Y)-labelled medicinal product is dependent on the specific medicinal product being radiolabelled. Information on radiation dosimetry of each different medicinal product following administration of the radiolabelled preparation will be 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 Yttrium (90Y) to the radiation dose following the administration of Yttrium (90Y)-labelled medicinal product or resulting from an accidental intravenous injection of Yttriga.
The dosimetry estimates were based on a rat distribution study and the calculations were effected in accordance with MIRD/ICRP 60 recommendations. Time-points for measurements were 5 min, 1, 6, 24, 96 and 360 hours.
Absorbed dose per unit activity administered (mGy/MBq):
| Organ | Adult (70 kg) | 15 years (50 kg) | 10 years (30 kg) | 5 years (17 kg) | 1 year (10 kg) | Newborn (5 kg) |
|---|---|---|---|---|---|---|
| Adrenals | 7,23 E-01 | 1,09 E+00 | 2,53 E+00 | 3,62 E+00 | 7,23 E+00 | 2,17 E+01 |
| Blood | 4,20 E-02 | 6,29 E-02 | 1,47 E-01 | 2,10 E-01 | 4,19 E-01 | 1,26 E+00 |
| Bone marrow | 2,58 E+00 | 3,88 E+00 | 9,05 E+00 | 1,29 E+01 | 2,58 E+01 | 7,75 E+01 |
| Brain | 8,60 E-03 | 1,29 E-02 | 3,01 E-02 | 4,30 E-02 | 8,60 E-02 | 2,58 E-01 |
| Carcass | 5,82 E-01 | 8,72 E-01 | 2,04 E+00 | 2,91 E+00 | 5,82 E+00 | 1,75 E+01 |
| Colon | 2,30 E-02 | 3,46 E-02 | 8,06 E-02 | 1,15 E-01 | 2,30 E-01 | 6,91 E-01 |
| Femur | 7,76 E+00 | 1,16 E+01 | 2,72 E+01 | 3,88 E+01 | 7,76 E+01 | 2,33 E+02 |
| Gastro-intestinal content | 1,22 E-01 | 1,83 E-01 | 4,26 E-01 | 6,09 E-01 | 1,22 E+00 | 3,66 E+00 |
| Heart | 2,53 E-01 | 3,79 E-01 | 8,85 E-01 | 1,26 E+00 | 2,53 E+00 | 7,59 E+00 |
| Ileum | 1,16 E-02 | 1,74 E-02 | 4,06 E-02 | 5,81 E-02 | 1,16 E-01 | 3,48 E-01 |
| Kidneys | 2,35 E+00 | 3,53 E+00 | 8,24 E+00 | 1,18 E+01 | 2,35 E+01 | 7,06 E+01 |
| Liver | 1,27 E+00 | 1,91 E+00 | 4,46 E+00 | 6,37 E+00 | 1,27 E+01 | 3,82 E+01 |
| Lungs | 4,23 E-01 | 6,34 E-01 | 1,48 E+00 | 2,11 E+00 | 4,23 E+00 | 1,27 E+01 |
| Ovaries | 3,33 E-01 | 4,99 E-01 | 1,17 E+00 | 1,66 E+00 | 3,33 E+00 | 9,99 E+00 |
| Pancreas | 7,90 E-02 | 1,18 E-01 | 2,76 E-01 | 3,95 E-01 | 7,90 E-01 | 2,37 E+00 |
| Skeletal muscle | 6,12 E-04 | 9,17 E-04 | 2,14 E-03 | 3,06 E-03 | 6,12 E-03 | 1,83 E-02 |
| Skin | 1,02 E-01 | 1,53 E-01 | 3,58 E-01 | 5,11 E-01 | 1,02 E+00 | 3,06 E+00 |
| Spleen | 4,90 E-01 | 7,36 E-01 | 1,72 E+00 | 2,45 E+00 | 4,90 E+00 | 1,47 E+01 |
| Stomach | 6,47 E-02 | 9,70 E-02 | 2,26 E-01 | 3,23 E-01 | 6,47 E-01 | 1,94 E+00 |
| Thymus | 7,34 E-02 | 1,10 E-01 | 2,57 E-01 | 3,67 E-01 | 7,34 E-01 | 2,20 E+00 |
| Thyroids | 9,99 E-01 | 1,50 E+00 | 3,50 E+00 | 5,00 E+00 | 9,99 E+00 | 3,00 E+01 |
| Urinary bladder | 3,62 E-01 | 5,44 E-01 | 1,27 E+00 | 1,81 E+00 | 3,62 E+00 | 1,09 E+01 |
| Uterus | 1,51 E-02 | 2,26 E-02 | 5,28 E-02 | 7,55 E-02 | 1,51 E-01 | 4,53 E-01 |
| Effective Dose (mSv/MBq) | 6,65 E-01 | 9,98 E-01 | 2,33 E+00 | 3,33 E+00 | 6,65 E+00 | 1,99 E+1 |
For this product the effective dose to a 70 kg adult resulting from an intravenously injected activity of 1 GBq is 665 mSv.
The presence of free Yttrium (90Y) chloride in the body after an inadvertent administration of Yttriga will lead to increased bone marrow toxicity and haematopoietic stern cell damage.
Therefore, in case of an inadvertent administration of Yttriga, the radiotoxicity for the patient must be reduced by immediate (i.e. within 1 hour) administration of preparations containing chelators like CaDTPA 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 Yttriga for labelling of carrier molecules for therapeutic purposes:
These chelating agents suppress yttrium radiotoxicity by an exchange between the calcium ion and the yttrium due to their capacity of forming water soluble complexes with the chelating ligands (DTPA, EDTA). These complexes are rapidly eliminated by the kidneys.
1 g 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 dextrose, or normal saline). 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 damage to the blood marrow.
The toxicity of the free Yttrium (90Y) due to in-vivo release from the labelled biomolecule in the body during therapy could be reduced by post-administration of chelating agents.
Up to 12 days from the date of manufacture.
Storage should be in accordance with national regulation on radioactive material.
Colourless type I glass vial of 3 ml with a V-shapped bottom or a colourless type I glass vial of 10 ml with a flat bottom with a silicon stopper, closed with an aluminium seal.
Pack size: 1 vial.
Not all presentations may be marketed.
The vial may contain high pressure due to radiolysis.
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