The Beginning and Development of the Theranostic Approach in Nuclear Medicine, as Exemplified by the Radionuclide Pair 86Y and 90Y

Abstract

In the context of radiopharmacy and molecular imaging, the concept of theranostics entails a therapy-accompanying diagnosis with the aim of a patient-specific treatment. Using the adequate diagnostic radiopharmaceutical, the disease and the state of the disease are verified for an individual patient. The other way around, it verifies that the radiopharmaceutical in hand represents a target-specific and selective molecule: the “best one” for that individual patient. Transforming diagnostic imaging into quantitative dosimetric information, the optimum radioactivity (expressed in maximum radiation dose to the target tissue and tolerable dose to healthy organs) of the adequate radiotherapeutical is applied to that individual patient. This theranostic approach in nuclear medicine is traced back to the first use of the radionuclide pair 86Y/90Y, which allowed a combination of PET and internal radiotherapy. Whereas the β-emitting therapeutic radionuclide 90Y (t½ = 2.7 d) had been available for a long time via the 90Sr/90Y generator system, the β+ emitter 86Y (t½ = 14.7 h) had to be developed for medical application. A brief outline of the various aspects of radiochemical and nuclear development work (nuclear data, cyclotron irradiation, chemical processing, quality control, etc.) is given. In parallel, the paper discusses the methodology introduced to quantify molecular imaging of 86Y-labelled compounds in terms of multiple and long-term PET recordings. It highlights the ultimate goal of radiotheranostics, namely to extract the radiation dose of the analogue 90Y-labelled compound in terms of mGy or mSv per MBq 90Y injected. Finally, the current and possible future development of theranostic approaches based on different PET and therapy nuclides is discussed.

Development of novel radionuclides for medical applications

“…As far as we know, this was the initiation of the concept of theranostic approach. The subsequent historical development has been described in a recent article …”

“…They involve precipitation and ion‐exchange chromatography, electrolysis, single‐column chromatography, multiple‐column chromatography, solvent extraction, and precipitation of the target element. A brief overview is given in Table and a detailed discussion elsewhere . Each method has its own advantages and disadvantages.…”

Labelling with positron emitters of pnicogens and chalcogens

“…The 8.4‐day half‐life of 72 Se makes the 72 Se/ 72 As pair ideal for a radioisotope generator from which 72 As can be obtained for about a month, potentially leading to portable availability of this PET radionuclide . In combination with the β − ‐emitting radionuclide arsenic‐77 ( 77 As), these 2 radioisotopes allowed their application as a “matched pair” for diagnostic and therapeutic radiopharmaceuticals, if the chemistry to incorporate them into physiologically stable molecules is developed, as first demonstrated for the yttrium‐86/yttrium‐90 pair and recently reviewed in detail …”

Cross‐Isotopic Bioorthogonal Tools as Molecular Twins for Radiotheranostic Applications

“…[14][15][16][17][18][19][20] However, 131 I-radiopharmaceuticals suffer from disadvantages such as poor availability,i nsufficient in vivo stability, and challenging radiochemistry;t hus limiting broad application. [25][26][27] To circumvent problemsr elated to the availability of chemically matching radioisotopes with required specific properties, "theranostic relatives" that utilize different elements are frequently used in clinical practice. However,t hese approaches are still limitedd ue to the poor availability and/or challenging production of radioisotopes such as 86 Ya nd 47 Sc.…”

“…[21][22][23][24] Yttrium ( 86 Yfor diagnostics, 90 Yfor therapy)o rs candium ( 43 Sc/ 44 Sc and 47 Sc) isotopes can be used to design chemically identical theranostics. [25][26][27] To circumvent problemsr elated to the availability of chemically matching radioisotopes with required specific properties, "theranostic relatives" that utilize different elements are frequently used in clinical practice. [25][26][27] To circumvent problemsr elated to the availability of chemically matching radioisotopes with required specific properties, "theranostic relatives" that utilize different elements are frequently used in clinical practice.…”