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
| Autor: | Andreas Türler, Maruta Bunka, Konstantin Zhernosekov, Roger Schibli, Cindy R. Fischer, Josefine Reber, Cristina Müller |
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| Rok vydání: | 2013 |
| Předmět: |
Ion chromatography
Lutetium KB Cells Heterocyclic Compounds 1-Ring Mice chemistry.chemical_compound Folic Acid Pharmacokinetics In vivo Animals Humans DOTA Radiology Nuclear Medicine and imaging Chelating Agents Radioisotopes Radiochemistry business.industry Cyclotrons Beta Particles chemistry Folate receptor Isotope Labeling Positron-Emission Tomography Radionuclide therapy Feasibility Studies Female Specific activity Nuclear medicine business Scandium Conjugate |
| Zdroj: | Journal of Nuclear Medicine. 54:2168-2174 |
| ISSN: | 2159-662X 0161-5505 |
| DOI: | 10.2967/jnumed.113.123810 |
| Popis: | 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 = 3.97 h, average β(+) energy [Eβ(+)av] = 632 keV) as a valuable alternative to (68)Ga (half-life = 68 min, Eβ(+)av = 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 cyclotron-produced (44)Sc and its in vitro and in vivo comparison with the (177)Lu-labeled pendant.(44)Sc was produced via the (44)Ca(p,n)(44)Sc nuclear reaction at a cyclotron (17.6 ± 1.8 MeV, 50 μA, 30 min) using an enriched (44)Ca target (10 mg (44)CaCO3, 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 miceUnder 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 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, (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.This study presents a high-yield 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)Lu-radionuclide tumor therapy. |
| Databáze: | OpenAIRE |
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