Accelerator-Based Production of Scandium Radioisotopes for Applications in Prostate Cancer: Toward Building a Pipeline for Rapid Development of Novel Theranostics.

In the field of nuclear medicine, the ß+ -emitting 43Sc and ß- -emitting 47Sc are promising candidates in cancer diagnosis and targeted radionuclide therapy (TRT) due to their favorable decay schema and shared pharmacokinetics as a true theranostic pair. Additionally, scandium is a group-3 transition metal (like 177Lu) and exhibits affinity for DOTA-based chelators, which have been studied in depth, making the barrier to implementation lower for 43/47Sc than for other proposed true theranostics. Before 43/47Sc can see widespread pre-clinical evaluation, however, an accessible production methodology must be established and each isotope's radiolabeling and animal imaging capabilities studied with a widely utilized tracer. As such, a simple means of converting an 18 MeV biomedical cyclotron to support solid targets and produce 43Sc via the 42Ca(d,n)43Sc reaction has been devised, exhibiting reasonable yields. The NatTi(γ,p)47Sc reaction is also investigated along with the successful implementation of chemical separation and purification methods for 43/47Sc. The conjugation of 43/47Sc with PSMA-617 at specific activities of up to 8.94 MBq/nmol and the subsequent imaging of LNCaP-ENZaR tumor xenografts in mouse models with both 43/47Sc-PSMA-617 are also presented.

Production and Use of the First-Row Transition Metal PET Radionuclides 43,44Sc, 52Mn, and 45Ti.

With the increasing focus on a more personalized approach to medicine using imaging techniques to select patients for targeted treatment or theranostic strategies, interest in the development of new radionuclides is expanding. Through the development of production and radiochemistry techniques, several new radiometals are being added to the toolbox of the nuclear imaging community. 43,44g,mSc, 52gMn, and 45Ti are all emerging transition metal radionuclides and will be discussed in this short review. Each of these nuclides has unique imaging characteristics and shows promise for the development of new molecular imaging agents.

Cyclotron production of (43)Sc for PET imaging.

BACKGROUND: Recently, significant interest in (44)Sc as a tracer for positron emission tomography (PET) imaging has been observed. Unfortunately, the co-emission by (44)Sc of high-energy γ rays (E γ = 1157, 1499 keV) causes a dangerous increase of the radiation dose to the patients and clinical staff. However, it is possible to produce another radionuclide of scandium-(43)Sc-having properties similar to (44)Sc but is characterized by much lower energy of the concurrent gamma emissions. This work presents the production route of (43)Sc by α irradiation of natural calcium, its separation and purification processes, and the labeling of [DOTA,Tyr3] octreotate (DOTATATE) bioconjugate. METHODS: Natural CaCO3 and enriched [(40)Ca]CaCO3 were irradiated with alpha particles for 1 h in an energy range of 14.8-30 MeV at a beam current of 0.5 or 0.25 µA. In order to find the optimum method for the separation of (43)Sc from irradiated calcium targets, three processes previously developed for (44)Sc were tested. Radiolabeling experiments were performed with DOTATATE radiobioconjugate, and the stability of the obtained (43)Sc-DOTATATE was tested in human serum. RESULTS: Studies of (nat)CaCO3 target irradiation by alpha particles show that the optimum alpha particle energies are in the range of 24-27 MeV, giving 102 MBq/µA/h of (43)Sc radioactivity which creates the opportunity to produce several GBq of (43)Sc. The separation experiments performed indicate that, as with (44)Sc, due to the simplicity of the operations and because of the chemical purity of the (43)Sc obtained, the best separation process is when UTEVA resin is used. The DOTATATE conjugate was labeled by the obtained (43)Sc with a yield >98 % at elevated temperature. CONCLUSIONS: Tens of GBq activities of (43)Sc of high radionuclidic purity can be obtainable for clinical applications by irradiation of natural calcium with an alpha beam.