Synthesis and evaluation of a [18F]formyl-Met-Leu-Phe derivative: A positron emission tomography imaging probe for bacterial infections

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:28

Article

Kimura, Hiroyuki^1,2  Yamauchi, Saki¹  Kawashima, Hidekazu^3,4  Arimitsu, Kenji^1,2  Yagi, Yusuke^1,2  Nakamoto, Yuji⁴  Togashi, Kaori⁴  Ono, Masahiro¹  Saji, Hideo¹ 

[1] Kyoto Univ, Dept Pathofunct Bioanal, Grad Sch Pharmaceut Sci, Sakyo Ku, 46-29 Yoshida Shimoadachi Cho, Kyoto 6068501, Japan

[2] Kyoto Pharmaceut Univ, Dept Analyt & Bioinorgan Chem, Yamashina Ku, 5 Nakauchi Cho, Kyoto 6078414, Japan

[3] Kyoto Pharmaceut Univ, Radioisotope Res Ctr, Yamashina Ku, 1 Misasagi Shichono Cho, Kyoto 6078412, Japan

[4] Kyoto Univ, Dept Diagnost Imaging & Nucl Med, Grad Sch Med, Sakyo Ku, 54 Shogoin Kawahara Cho, Kyoto 6068507, Japan

关键词: G protein-coupled formyl peptide receptor;    Positron emission tomography;    Bacterial infections;    Peptide probe;    F-18;   

DOI  :  10.1016/j.bmcl.2018.07.009

来源: Elsevier

【 摘 要 】

The tripeptide formyl-Met-Leu-Phe (fMLF) is a prototype of N-formylated chemotactic peptides for neutrophils owing to its ability to bind and activate the G protein-coupled formyl peptide receptor (FPR). Here, we developed an F-18-labeled fMLF derivative targeting FPR as a positron emission tomography (PET) imaging probe for bacterial infections. The study demonstrates that the fMLF derivative fMLFXYk(FB)k (X = Nle) has a high affinity for FPR (Ki = 0.62 +/- 0.13 nM). The radiochemical yield and purity of [F-18]fMLFXYk(FB)k were 16% and > 96%, respectively. The in vivo biodistribution study showed that [F-18]fMLFXYk(FB)k uptake was higher in the bacterial infected region than in the non-infected region. We observed considerably higher infection-tomuscle ratio of 4.6 at 60 min after [F-18]fMLFXYk(FB)k injection. Furthermore, small-animal PET imaging studies suggested that [F-18]fMLFXYk(FB)k uptake in the bacterial infected region was clearly visualized 60 min after injection.

【 授权许可】

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