Why is 177Lu Expected to Be So Important in Targeted Radionuclide Therapy?

The striking diffusion and exciting perspectives of 177Lu in targeted radionuclide therapy (TRT) are primarily attributed to the following.

  • The mean penetration range of β− particles emitted by 177Lu in soft tissue is 670 μm, making this radionuclide ideal for delivering energy to small volumes, including micrometastatic disease, and tumor cells near the surface of cavities. Lutetium-177 is found to be effective in localizing cytotoxic radiation in relatively small areas and proficient in destroying small tumors as well as metastatic lesions (typically less than 3 mm diameter) with less damage to surrounding normal tissue.
  • The emission of low-energy gamma photons enables imaging the biodistribution and excretion kinetics with the same radiolabeled preparation used for therapy and allows dosimetry to be performed before and during treatment as well. This property is important for “personalized” medicine for the development of “theranostic” agents for combined diagnostic and therapeutic use that can deliver therapy to individual cells in affected tissues.
  • The emission of moderate-energy beta β- particles as well as low-energy gamma photons results in a relatively low radiation dose and therefore offers the potential to handle relatively high 177Lu activity levels during radiopharmaceutical preparation and formulation of radiopharmaceuticals as well as during patient administration.
  • Lutetium exclusively exists in the +3 oxidation state, which precludes any solution chemistry reduction-oxidation complications and commonly forms nine coordination complexes. This property therefore provides the potential for radiolabeling a variety of molecular carriers, which include small molecules, and peptides, proteins and antibodies with the specific desired characteristics for therapy. The chemical characteristics of Lu+3 are suitable for peptide and protein radiolabeling by attachment of a bifunctional chelating agent (BFCA) through a metabolically resistant covalent bond.
  • The 6.65-day half-life of 177Lu offers extended time periods, which may be required for the use of more sophisticated procedures to radiolabel and purify 177Lu-labeled radiopharmaceuticals, and for performing quality control and administration. The use of a longer lived therapeutic radionuclide such as 177Lu is particularly well suited for the radiolabeling of antibodies that have slow targeting kinetics.
  • The relatively long 6.65-day physical half-life of 177Lu not only minimizes decay loss, which may be encountered during the transportation and distribution to users, but also provides excellent logistical advantages for shipment to sites distant from the reactor production facility as well as radionuclide-processing facilities.

A wide range of 177Lu radiopharmaceuticals has been successfully developed and evaluated. The in vivo applications of key 177Lu radiopharmaceuticals for a variety of therapeutic procedures include peptide receptor radionuclide therapy [11–26], bone pain palliation [27–33], radiation synovectomy [34–39] and radioimmonutherapy [40–46]. There is a steadily expanding list of 177Lu-labeled radiopharmaceuticals that is currently being evaluated at the preclinical research or at product development stages; these may potentially be used in vivo in humans for evaluation for radionuclide therapy [1–3]. A summary of key 177Lu-labeled radiopharmaceuticals currently used in TRT is depicted in Table 1.

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