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.

In recent years, implementation of 68 Ga-radiometalated peptides for PET imaging of cancer has attracted the attention of clinicians. Herein, we propose the use of 44 Sc (half-life 5 3.97 h, average b 1 energy [Eb 1 av ] 5 632 keV) as a valuable alternative to 68 Ga (half-life 5 68 min, Eb 1 av 5 830 keV) for imaging and dosimetry before 177 Lu-based radionuclide therapy. The aim of the study was the preclinical evaluation of a folate conjugate labeled with cyclotronproduced 44 Sc and its in vitro and in vivo comparison with the 177 Lulabeled pendant. Methods: 44 Sc was produced via the 44 Ca(p,n) 44 Sc nuclear reaction at a cyclotron (17.6 6 1.8 MeV, 50 mA, 30 min) using an enriched 44 Ca target (10 mg 44 CaCO 3 , 97.00%). Separation from the target material was performed by a semiautomated process using extraction chromatography and cation exchange chromatography. Radiolabeling of a DOTA-folate conjugate (cm09) was performed at 95°C within 10 min. The stability of 44 Sc-cm09 was tested in human plasma. 44 Sc-cm09 was investigated in vitro using folate receptor-positive KB tumor cells and in vivo by PET/CT imaging of tumor-bearing mice Results: Under the given irradiation conditions, 44 Sc was obtained in a maximum yield of 350 MBq at high radionuclide purity (.99%). Semiautomated isolation of 44 Sc from 44 Ca targets allowed formulation of up to 300 MBq of 44 Sc in a volume of 200-400 mL of ammonium acetate/HCl solution (1 M, pH 3.5-4.0) within 10 min. Radiolabeling of cm09 was achieved with a radiochemical yield of greater than 96% at a specific activity of 5.2 MBq/nmol. In vitro, 44 Sc-cm09 was stable in human plasma over the whole time of investigation and showed folate receptor-specific binding to KB tumor cells. PET/CT images of mice injected with 44 Sc-cm09 allowed excellent visualization of tumor xenografts. Comparison of cm09 labeled with 44 Sc and 177 Lu revealed almost identical pharmacokinetics. Conclusion: This study presents a highyield production and efficient separation method of 44 Sc at a quality suitable for radiolabeling of DOTA-functionalized biomolecules. An in vivo proof-of-concept study using a DOTA-folate conjugate demonstrated the excellent features of 44 Sc for PET imaging. Thus, 44 Sc is a valid alternative to 68 Ga for imaging and dosimetry before 177 Luradionuclide tumor therapy. In the past decade, applications of radiometal-based PET have rapidly increased, particularly for oncologic imaging purposes (1). Clinical implementation of 68 Ga-labeled somatostatin analogs (e.g., 68 Ga-DOTATATE, 68 Ga-DOTATOC) for imaging of neuroendocrine tumors has raised attention because of the excellent imaging quality that can be achieved and the on-site availability of 68 Ga (half-life [T 1/2 ] 5 68 min, average b 1 energy [Eb 1 av ] 5 830 keV, intensity 5 89%) by the 68 Ge/ 68 Ga generator (2-6). Somatostatin receptor-targeted PET is currently used for dosimetry before application of 177 Lu-based radionuclide therapy (7). These facts have established the basis of a new era of PET applicat...

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