Rhenium-188 as a therapeutic radionuclide in low-income and middle-income countries

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Theranostics in the field of nuclear medicine stands poised at the threshold of influencing the course of medical therapies, especially in the forthcoming era in which targeted and personalized medicine would be the norm. This aforementioned paradigm is possibly best suited here than in any other medical specialty, and the best example of this is the use of low-dose iodine-131 for diagnosis and high-dose iodine-131 for therapy in thyroid cancer.
We believe that we have moved several steps forward into newer molecules giving us innumerable theranostic possibilities. However, the possibility of running any regional nuclear medicine programme as a successful one will depend on the continuous and cost-effective availability of newer radioactive isotopes. The real challenge will be sustaining the ability to harness their potential with suitable conjugates to match the need of diagnosis or therapy. Although there are a large number of therapeutic radionuclides, the availability of these radionuclides in several parts of the world is doubtful and the cost varies heavily depending on the country and local issues. An exciting possibility of using 188W/188Re generator as a ready source for providing the therapeutic radionuclide, rhenium-188 came up, thanks to the efforts of the International Atomic Energy Agency (IAEA) under the leadership of the very well known Dr. A.K. Padhy. The IAEA organized several Coordinated Research Projects, workshops and training courses to propagate the use of rhenium-188 (188Re) for therapy since then. The main focus was on the use of 188Re-lipiodol for the treatment of hepatocellular carcinoma, a widely prevalent disease in developing countries, with a special emphasis on Asia where the socioeconomic burden was maximal. Although the initial trials yielded results on par with yttrium-90 particulates, this therapy was not pursued further because of the lack of a concerted effort from any of the commercial vendors to propagate it.
In India, we attempted a revival of transarterial radioembolization with 188Re-labelled lipiodol in 2013 at our center. Back then, available options for transarterial radioembolization were exorbitantly expensive and limited to a few patients out of the deserving thousands. Armed with good results obtained in the IAEA trials and support from WARMTH, we treated more than 100 cases with 188Re-labelled lipiodol and the results are impressive. To run a cost-effective program, we also expanded the therapeutic use of 188Re to include bone pain palliation therapy, radiosynovectomy and intravascular brachytherapy. We are now conducting pilot studies with 188Re-labelled prostate-specific membrane antigen targeting small molecules and somatostatin receptor targeting peptides for treating prostate and neuroendocrine cancers, respectively.
By holding numerous training sessions, workshops and the first Rhenium World Congress, we opened avenues enabling free and constant dissemination of our knowledge and experience. It is heartening that India currently leads the world in the number of centers using 188Re for clinical services as well as for research. This has been possible because of the seamless integration of technology and chemistry developed from many parts of the world and given to us purely on a collaborative platform leaving aside commercial interests.
There are two major issues limiting the widespread use of 188Re as a therapeutic workhorse. The first and foremost is the availability of adequate quantity of tungsten-188, as there is only one reactor in the world (SM3 reactor in Dimitrovgrad, Russia) making tungsten-188, which is suitable for generator production. However, there is adequate capacity available with them to produce tungsten-188 sufficient for making several hundreds of generators annually. The second issue is the nonavailability of commercially viable generator production facilities where a large number of generators can be prepared and supplied to the users.
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