Cyclotron production of 43Sc for PET imaging

Abstract

BackgroundRecently, significant interest in 44Sc as a tracer for positron emission tomography (PET) imaging has been observed. Unfortunately, the co-emission by 44Sc of high-energy γ rays (Eγ = 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—43Sc—having properties similar to 44Sc but is characterized by much lower energy of the concurrent gamma emissions. This work presents the production route of 43Sc by α irradiation of natural calcium, its separation and purification processes, and the labeling of [DOTA,Tyr3] octreotate (DOTATATE) bioconjugate.MethodsNatural CaCO3 and enriched [40Ca]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 43Sc from irradiated calcium targets, three processes previously developed for 44Sc were tested. Radiolabeling experiments were performed with DOTATATE radiobioconjugate, and the stability of the obtained 43Sc-DOTATATE was tested in human serum.ResultsStudies of natCaCO3 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 43Sc radioactivity which creates the opportunity to produce several GBq of 43Sc. The separation experiments performed indicate that, as with 44Sc, due to the simplicity of the operations and because of the chemical purity of the 43Sc obtained, the best separation process is when UTEVA resin is used. The DOTATATE conjugate was labeled by the obtained 43Sc with a yield >98 % at elevated temperature.ConclusionsTens of GBq activities of 43Sc of high radionuclidic purity can be obtainable for clinical applications by irradiation of natural calcium with an alpha beam.

47Sc production development by cyclotron irradiation of 48Ca

“…43 Sc can be produced either by the 43 Ca(p,n) [11], or by 42 Ca(d,n) [12] reaction, but unfortunately the cost of enriched calcium targets is very expensive. The more promising method of 43 Sc production is alpha irradiation of natural calcium target through the 40 Ca(α,p) and 40 Ca(α,n) channels has been mentioned in recently published paper [13]. …”

Radiometals for imaging and theranostics, current production, and future perspectives

“…In order to understand the pharmacokinetics of these compounds at longer time points (days), diagnostic radiometals with longer half-lives must be used. 89 Zr (T 1/2 = 3.27 d) has been emerging as a well-suited nuclide for the imaging of intact antibodies and nanoparticles. Many studies have illustrated the utility of 89 Zr-labelled agents for PET imaging in both preclinical and clinical research studies.…”

“…89 Zr (T 1/2 = 3.27 d) has been emerging as a well-suited nuclide for the imaging of intact antibodies and nanoparticles. Many studies have illustrated the utility of 89 Zr-labelled agents for PET imaging in both preclinical and clinical research studies. 104-107 89 Zr is produced via the 89 Y(p,n) 89 Zr nuclear reaction on Y metal targets.…”

“…[1][2][3] The radiometals have played an important role since the early days of nuclear medicine. For example, 89 Sr has been used as 89 Sr 2+ ion because of its biological behaviour, which is similar to that of calcium. 4 Presently, the use of 223 Ra, the first alpha emitter to be granted marketing authorization (Xofigo), 5 is based on the same principle.…”

Re‐thinking the role of radiometal isotopes: Towards a future concept for theranostic radiopharmaceuticals

“…In this respect, it must be noted that the intense (>80%), high‐energy (>900 keV) gamma lines of some PET radiometals, namely 44 Sc, 89 Zr, and 86 Y, further limit their routine applicability for reasons of radiation protection (above all, due to high doses to production and nursing personnel) and may compromise image quality . Therefore, the isotope 43 Sc which lacks such gamma emission is currently brought forward as a replacement for 44 Sc. Because it is also produced in cyclotrons, 43 Sc again will have to compete economically and practically with 18 F, but it cannot be ruled out that wide availability of 43 Sc could initiate a dynamic development whose results cannot be foreseen at this time.…”