Towards Radionuclide Cancer Therapy with High Purity ¹⁷⁷Lu from Enriched ¹⁷⁶Yb Samples

Radiopharmaceuticals labelled with radionuclides of high radionuclide purity in nuclear medicine that emit gamma-rays and beta-rays have been used for diagnosis imaging of diseases and therapy in cancer treatments, respectively. Internal radiation therapy is performed using radiation doses to kill cancer cells and shrink tumors. A personalized medicine treatment that combines diagnosis and therapy has become important for a patient, in which information about the patient’s genes is used. A personalized medicine treatment is performed using radionuclide pairs appropriate for both diagnosis and therapy in the same patients, requiring us to develop a variety of radionuclides.

Recently, significant interest has arisen in ¹⁷⁷Lu, currently produced in reactors, owing to successful treatments in patients with neuroendocrine tumors, which appear everywhere in the body, using ¹⁷⁷Lu-labelled radiopharmaceuticals; this success encourages further study of ¹⁷⁷Lu production in accelerators toward widespread medical applications of ¹⁷⁷Lu. Indeed, the excitation functions of the ¹⁷⁶Yb(d,p)¹⁷⁷Yb®¹⁷⁷Lu and ¹⁷⁶Yb(d,n)¹⁷⁷Lu (hereafter ¹⁷⁶Yb(d,x)¹⁷⁷Lu) reaction have been measured using a natural Yb (^natYb) sample but not an enriched ¹⁷⁶Yb sample. Hence, radionuclide purity of ¹⁷⁷Lu radionuclide is low because of many impurity radionuclides of Lu arising from seven stable isotopes, ¹⁶⁸Yb-¹⁷⁶Yb, present in ^natYb. Even with the use of highly enriched samples, no radionuclide sample is 100% pure and all contain some impurity radionuclides resulting from the production process by nuclear reactions.

A method was developed to estimate the isotopic compositions of enriched ¹⁷⁶Yb samples required to produce ¹⁷⁷Lu with a high radionuclide purity using the ¹⁷⁶Yb(d,x)¹⁷⁷Lu reaction. First, the estimation was done by deriving excitation functions of individual reactions for producing all aforementioned impurity Lu radionuclides that were obtained by fitting the measured excitation functions of the ^natYb(d,x)Lu reactions with an appropriate function form (see Fig. 1). Second, the yields of all Lu radionuclides that were produced by irradiating enriched ¹⁷⁶Yb samples with several isotopic compositions of Yb present in enriched ¹⁷⁶Yb samples with deuteron beams were estimated. The ¹⁷⁷Lu radionuclide purity for the 99.90% and 97.60% enriched ¹⁷⁶Yb samples at 2.5 days after the end of irradiation was estimated to be high, that is, > 98% and > 99% at the deuteron energy of 20 and 15 MeV, respectively. The resultant radionuclide ¹⁷⁷Lu would play an important role in promoting its widespread use for a variety of therapeutic applications. This finding to utilize measured excitation functions of nuclear reactions with natural samples would play an important role in producing a variety of medical radionuclides with a high radionuclide purity.

(written by Yasuki Nagai on behalf of all authors)