Overview of Yttrium-90 (Y-90) and Lutetium-177 (Lu-177) radiopharmaceuticals

In radiopharmaceutical therapy, radionuclides are usually attached to tumour-affine molecules and the tumour is thus irradiated in a targeted manner. Iodine-131 (131I) has been used for decades to treat thyroid carcinoma [1]. In recent years, other radiopharmaceuticals with a high tumour affinity have been added. In addition to iodine-131 (131I), more and more yttrium-90 (90Y) and lutetium-177 (177Lu) are being routinely used in targeted radionuclide therapy.

 

Theranostics

In theranostics (also known as theragnostics), radioactive substances are used for the diagnosis and therapy of various diseases [2]. The term theranostics consists of the two words: therapy and diagnostics. Theranostics are usually provided with diagnostical or therapeutical radionuclides using molecular target vectors (e.g. peptides). A classic example of this is the use of a 68Ga-labelled tracer for diagnostics and a therapeutic radionuclide such as 90Y or 177Lu for therapy [3].

Properties of 90Y and 177Lu

The half-life (t1/2) of 90Y with 64.1 hours, is shorter than the half-life of 177Lu with 6.65 days [4.5]. 90Yas a high-energy β-emitter with a maximum penetration depth of 11 mm has more energy than 177Luwith lower β-energy with a maximum penetration depth of 1.7 mm [5].

90Y and 177Lu getting more important

The clinical application of therapeutic radionuclides is often determined by the availability of radionuclides [4]. In the best case, a generator is available, such as for 90Y. Examples of 90Yand 177Lutherapeuticsl radionuclides are the somatostatin analogues 90Y-DOTATOC and 177Lu-DOTATATE for neuroendocrine tumours and 177Lu-labelled PSMA ligand for metastatic prostate cancer [6]. The combination of 90Y and 177Lu is also described in the literature. Kunikowska et al. showing in the study the combined administration of 90Y/177Lu-DOTATATE [7]. The authors concluded that this could lead to personalized medicine in radiopharmacy.
Frost et al. compared the efficacy of 90Y and 177Lu-CD20 therapy in one study and found 90Y therapy to be more effective [8].

Advantages and disadvantages of 90Yand 177Lu

The chemical properties of the radiometal should allow stable coordination using standard chelators. The energy of the radionuclide is also important. An advantage of 90Ycompared to 177Luis the higher β-energy and range, which makes this radionuclide preferable for therapy depending on the application. However, the high energy can lead to radiolysis effects. The molecule must therefore be carefully selected and adapted.
Another advantage of 90Yis the almost pure β-radiation. However, the absence of the gamma-photon makes conventional scintigraphy rather difficult [9].

Depending on the clinical indication and logistics, the half-life of the radionuclide must be taken into account, which is an advantage of 177Luwith its longer half-life of 6.65 days.
Another important point is the availability of the radionuclides. A generator is available for 90Y. 177Lu on the other hand, must be produced and transported to the place of synthesis. If the clinical trials for 177Lu will be with a positive outcome, the demand for 177Lu will increase, especially for the 177Lu-PSMA therapy, as Hehakaya wrote [10]. This should lead to more manufacturers entering the market to fill the gap.

Testing for sterility of 90Y and 177Lu radiopharmaceuticals

90Y-and 177Lu- radiotherapeutics administered to patients must be tested for sterility according to the European Pharmacopoeia (Ph. Eur). Even if the energy of the radionuclides is higher, there is no auto-sterilization effect as described in the article Sterility testing of radiopharmaceuticals[11]. You can find further information on the topic of sterility testing of radiopharmaceuticals:
Sterility testing of radiopharmaceuticals

RADIOSTER now offers sterile testing for 90Yfollowing the successful establishment of sterile testing of 177Lu radiotherapeutic agents.

If you would like to test other radionuclides, please contact us. We are constantly expanding the list of radionuclides.

Further information can be found on www.cup-freitag.de/radioster

Contact us

The experts at CUP Laboratorien Dr. Freitag GmbH will be happy to advise you with their knowledge.

Stefan Knolle (M.Sc.)
radioster@cup-freitag.de


Literature

[1]     Mazzaferri et al., Am J Med. 1994;97:418-28
[2]     Xie et al., Advanced Drug Delivery Reviews. 2010;62(11):1064–79
[3]     de Jong et al., J. Nucl. Med. 2005; 46:13S-17S
[4]     Müller et al., J. Nucl Med. 2017; 58:91S–96S
[5]     Yeong et al., Biomed & Biotechnol. 2014;15(10):845-63
[6]     Champion et al., Theranostics. 2016;6(10):1611-18
[7]     Brans et al., Eur J Nucl Med Mol Imaging. 2011;38:1785-87
[8]     Frost et al., 2015 PLOS One, DOI:10.1371/journal.pone.0120561
[9]     Wright et al. 2015: dx.doi.org/10.1155/2015/481279
[10]    Hehakaya et al. Eur J Nucl Med Mol Imaging. 2020: https://doi.org/10.1007/s00259-020-05102-4
[11]    Sterility testing of radiopharmaceuticals

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