RT Journal Article
SR Electronic
T1 Synthesis and Characterization of <sup>18</sup>F-Interleukin-8 Using a Cell-Free Translation System and 4-<sup>18</sup>F-Fluoro-<span class="sc">l</span>-Proline
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 634
OP 639
DO 10.2967/jnumed.115.162602
VO 57
IS 4
A1 Ryuichi Harada
A1 Shozo Furumoto
A1 Takeo Yoshikawa
A1 Yoichi Ishikawa
A1 Katsuhiko Shibuya
A1 Nobuyuki Okamura
A1 Kiichi Ishiwata
A1 Ren Iwata
A1 Kazuhiko Yanai
YR 2016
UL http://jnm.snmjournals.org/content/57/4/634.abstract
AB Macromolecules such as proteins are attracting increasing interest for molecular imaging. We previously proposed a novel strategy for preparing macromolecules labeled with a PET radionuclide, 11C, using a cell-free translation system with 11C-methionine. However, macromolecules tend to exhibit slower kinetics, thus requiring a longer scanning time. Here, we expand our strategy using 18F, which has a longer half-life, with the cell-free translation system with 4-18F-fluoro-l-proline (18F-FPro). We evaluated 18F-interleukin-8 (18F-IL-8) produced by this method in vitro and in vivo to provide a proof of concept of our strategy. Methods: We tested some fluorinated amino acids to be incorporated into a protein. Trans-18F-FPro was radiolabeled from the corresponding precursor. 18F-IL-8 was produced using the cell-free translation system with trans-18F-FPro instead of natural l-proline with incubation at 37°C for 120 min. An in vitro binding assay of 18F-IL-8 was performed using IL-8 receptor–expressing cells. After intravenous administration of 18F-IL-8, in vivo PET imaging of IL-8 receptor–expressing xenograft-bearing mice was performed using a small-animal PET system. Results: FPro was identified as an amino acid incorporated into the protein. 18F-IL-8 was successfully prepared using the cell-free translation system and trans-18F-FPro with the radiochemical yield of 1.5% (decay-corrected) based on trans-18F-FPro. In vitro binding assays of 18F-IL-8 demonstrated its binding to IL-8 receptor. In vivo PET imaging demonstrated that 18F-IL-8 clearly accumulated in IL-8 receptor–expressing xenografts in mice, unlike trans-18F-FPro. Conclusion: 18F-IL-8 produced by this method binds to IL-8 receptors in vitro, and 18F-IL-8 PET clearly visualizes its target receptor–expressing xenograft in vivo. Therefore, this technique might be useful for labeling macromolecules and performing preclinical evaluations of proteins of interest in vitro and in vivo.