Efficient synthesis of (2<i>S</i>)-<i>tert</i>-butyl 2-(2-bromopropanamido)-5-oxo-5-(tritylamino)pentanoate as a precursor of PET radiotracer [¹⁸F]FPGLN

<p>This study describes a convenient protocol for the synthesis of (2<i>S</i>)-<i>tert</i>-butyl 2-(2-bromopropanamido)-5-oxo-5-(tritylamino)pentanoate, which can serve as an appropriate precursor of (2<i>S</i>)-5-amino-2-(2-[¹⁸F]fluoropropanamido)-5-oxopentanoic acid (<i>N</i>-(2-[¹⁸F]fluoropropionyl)-L-glutamine, [¹⁸F]FPGLN) for tumor positron emission tomography imaging. Five-step synthesis starting from L-glutamine provided the desired precursor with high yields. In addition, a simple method for the preparation of [¹⁸F]FPGLN from this easily available precursor was developed using a two-step ¹⁸F-labeling strategy.</p

Biodistribution of ¹⁸F-FP-PEG₂-β-Glu-RGD₂ in Normal Mice^a.

<p>^aMeans ± SD (n = 4). Data are average % ID/g.</p><p>Biodistribution of ¹⁸F-FP-PEG₂-β-Glu-RGD₂ in Normal Mice<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138675#t001fn001" target="_blank">^a</a>.</p

Biodistribution of ₁₈F-FP-PEG₂-β-Glu-RGD₂ in Nude Mice Bearing A549 Xenografts^a.

<p>^aMeans ± SD (n = 4). Data are average % ID/g.</p><p>Biodistribution of ₁₈F-FP-PEG₂-β-Glu-RGD₂ in Nude Mice Bearing A549 Xenografts<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138675#t002fn001" target="_blank">^a</a>.</p

MicroPET-CT fused images of orthotopic transplanted C6 brain glioma model rats at 60 min post-injection of ¹⁸F-FDG and ¹⁸F-FP-PEG₂-β-Glu-RGD₂.

<p>(The red arrows indicate the tumor).</p

Radiosynthesis of ¹⁸F-FP-PEG₂-β-Glu-RGD₂.

<p>Radiosynthesis of ¹⁸F-FP-PEG₂-β-Glu-RGD₂.</p

Synthetic route of Fmoc-β-Glu(OSu)-OSu.

<p>Synthetic route of Fmoc-β-Glu(OSu)-OSu.</p

Tumor uptake of ¹⁸F-FP-PEG₂-β-Glu-RGD₂ was inhibited by co-injection of an excess dose of RGD.

<p>(A) MicroPET-CT images of PC-3 prostate tumor-bearing mice without/with a blocking dose of RGD (4 mg/kg body weight) at 60 min after injection of ¹⁸F-FP-PEG₂-β-Glu-RGD₂. (The red arrows indicated PC-3 prostate tumor). (B) The tumor uptake of ¹⁸F-FP-PEG₂-β-Glu-RGD₂ in PC-3 prostate tumor and PC-3 prostate tumor treated with cold RGD blocking at 60 min after injection (mean ±SD, n = 4 per group).</p

Chemical structures of ¹⁸F-PP-PRGD₂, ¹⁸F-FB-AEADP-BBN-RGD, ¹⁸F-FP-PEG₂-β-Glu-RGD₂, and Fmoc-β-Glu(OSu)-OSu.

<p>Chemical structures of ¹⁸F-PP-PRGD₂, ¹⁸F-FB-AEADP-BBN-RGD, ¹⁸F-FP-PEG₂-β-Glu-RGD₂, and Fmoc-β-Glu(OSu)-OSu.</p

Small animal PET imaging and quantification.

<p>(A) MicroPET-CT imaging of PC-3 prostate tumor-bearing mice at 30, 60, 90, and 120 min after injection of ¹⁸F-FP-PEG₂-β-Glu-RGD₂. (The red arrows indicated PC-3 prostate tumor). (B) MicroPET-CT imaging of A549 human lung adenocarcinoma-bearing mice at 30, 60, 90, and 120 min after injection of ¹⁸F-FP-PEG₂-β-Glu-RGD₂. (The red arrows indicated A549 lung adenocarcinoma). (C) Time-activity curves of PC-3 prostate tumor, A549 lung adenocarcinoma and muscle after intravenous injection of ¹⁸F-FP-PEG₂-β-Glu-RGD₂.</p