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• W2156852064 abstract "In recent years, implementation of ⁶⁸Ga-radiometalated peptides for PET imaging of cancer has attracted the attention of clinicians. Herein, we propose the use of ⁴⁴Sc (half-life = 3.97 h, average β⁺ energy [Eβ⁺_av] = 632 keV) as a valuable alternative to ⁶⁸Ga (half-life = 68 min, Eβ⁺_av = 830 keV) for imaging and dosimetry before ¹⁷⁷Lu-based radionuclide therapy. The aim of the study was the preclinical evaluation of a folate conjugate labeled with cyclotron-produced ⁴⁴Sc and its in vitro and in vivo comparison with the ¹⁷⁷Lu-labeled pendant. <b>Methods:</b>⁴⁴Sc was produced via the ⁴⁴Ca(p,n)⁴⁴Sc nuclear reaction at a cyclotron (17.6 ± 1.8 MeV, 50 μA, 30 min) using an enriched ⁴⁴Ca target (10 mg ⁴⁴CaCO₃, 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 ⁴⁴Sc-cm09 was tested in human plasma. ⁴⁴Sc-cm09 was investigated in vitro using folate receptor–positive KB tumor cells and in vivo by PET/CT imaging of tumor-bearing mice <b>Results:</b> Under the given irradiation conditions, ⁴⁴Sc was obtained in a maximum yield of 350 MBq at high radionuclide purity (>99%). Semiautomated isolation of ⁴⁴Sc from ⁴⁴Ca targets allowed formulation of up to 300 MBq of ⁴⁴Sc in a volume of 200–400 μL 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, ⁴⁴Sc-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 ⁴⁴Sc-cm09 allowed excellent visualization of tumor xenografts. Comparison of cm09 labeled with ⁴⁴Sc and ¹⁷⁷Lu revealed almost identical pharmacokinetics. <b>Conclusion:</b> This study presents a high-yield production and efficient separation method of ⁴⁴Sc 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 ⁴⁴Sc for PET imaging. Thus, ⁴⁴Sc is a valid alternative to ⁶⁸Ga for imaging and dosimetry before ¹⁷⁷Lu-radionuclide tumor therapy." @default.
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• W2156852064 date "2013-11-06" @default.
• W2156852064 modified "2023-10-03" @default.
• W2156852064 title "Promises of Cyclotron-Produced ⁴⁴Sc as a Diagnostic Match for Trivalent β⁻-Emitters: In Vitro and In Vivo Study of a ⁴⁴Sc-DOTA-Folate Conjugate" @default.
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• W2156852064 doi "https://doi.org/10.2967/jnumed.113.123810" @default.
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