Promising Prospects for ⁴⁴Sc-/⁴⁷Sc-Based Theragnostics: Application of ⁴⁷Sc for Radionuclide Tumor Therapy in Mice

Abstract

In recent years, 47 Sc has attracted attention because of its favorable decay characteristics (half-life, 3.35 d; average energy, 162 keV; Eγ, 159 keV) for therapeutic application and for SPECT imaging. The aim of the present study was to investigate the suitability of 47 Sc for radionuclide therapy in a preclinical setting. For this purpose a novel DOTA-folate conjugate (cm10) with an albumin-binding entity was used. Methods: 47 Sc was produced via the 46 Ca(n,γ) 47 Ca! b − 47 Sc nuclear reaction at the high-flux reactor at the Institut Laue-Langevin. Separation of the 47 Sc from the target material was performed by a semi-automated process using extraction chromatography and cation exchange chromatography. 47 Sc-labeled cm10 was tested on folate receptor-positive KB tumor cells in vitro. Biodistribution and SPECT imaging experiments were performed in KB tumor-bearing mice. Radionuclide therapy was conducted with two groups of mice, which received either 47 Sc-cm10 (10 MBq) or only saline. Tumor growth and survival time were compared between the two groups of mice. Results: Irradiation of 46 Ca resulted in approximately 1.8 GBq of 47 Ca, which subsequently decayed to 47 Sc. Separation of 47 Sc from 47 Ca was obtained with 80% yield in only 10 min. The 47 Sc was then available in a small volume (∼500 μL) of an ammonium acetate/HCl (pH 4.5) solution suitable for direct radiolabeling. 47 Sc-cm10 was prepared with a radiochemical yield of more than 96% at a specific activity of up to 13 MBq/nmol. In vitro 47 Sccm10 showed folate receptor-specific binding and uptake into KB tumor cells. In vivo SPECT/CT images allowed the visualization of accumulated radioactivity in KB tumors and in the kidneys. The therapy study showed a significantly delayed tumor growth in mice, which received 47 Sc-cm10 (10 MBq, 10 Gy) resulting in a more than 50% increase in survival time, compared with untreated control mice. Conclusion: With this study, we demonstrated the suitability of using 47 Sc for therapeutic purposes. On the basis of our recent results obtained with 44 Sc-folate, the present work confirms the applicability of 44 Sc/ 47 Sc as an excellent matched pair of nuclides for PET imaging and radionuclide therapy.

Cyclotron production of high purity 44m,44 Sc with deuterons from 44 CaCO 3 targets

“…Most probes may be more efficient if combined with new radionuclides. Recently, the scandium chemistry has revealed a growing interest with an increasing number of papers available on scandium: from 44 Ti/ 44 Sc generator [1][2][3][4], from neutron irradiated Ti [5,6], cyclotron produced 44m Sc/ 44 Sc [7][8][9], nat Sc [10], 46 Sc [11,12] or 47 Sc [13][14][15]. Among them, the most promising is 44 Sc with a half-life (T 1/2 ) of 3.97 h and mean positron energy of 0.6 MeV ideal for PET cameras.…”

Half-lives of La132 and La135

“…Theranostic pairs allow an accurate calculation of dosimetry in internal radionuclide therapy, thereby providing a prediction for the efficacy of treatment (see, for example, the theranostic terbium isotopes [1]). However, inaccuracy in halflife values in either isotope will result in a miscalculation of dosimetry and will systematically lower the predictive capability.…”

Cyclotron production of 44Sc: From bench to bedside

“…Importantly, there is also a relevant "therapeutic match" of the same element, namely, 47 Sc (T 1/2 = 3.4 d, Eβ -av = 162 keV, main Eγ = 159.4 keV, I = 68.3%) which has excellent β --decay properties and has, therefore, been proposed for theragnostic applications together with 44 Sc [9].…”