Development of PEGylated peptide probes conjugated with ¹⁸F-labeled BODIPY for PET/optical imaging of MT1-MMP activity

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• 作者：Naoya Kondo^a ; Takashi Temma^a ; ^b ; Jun Deguchi^a ; Kohei Sano^a ; Masahiro Ono^a ; Hideo Saji^a ; ^{hsaji@pharm.kyoto-u.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：MT1-MMP ; Positron emission tomography (PET) ; Optical imaging ; Polyethylene glycol (PEG) ; Peptide
• 刊名：Journal of Controlled Release
• 出版年：2015
• 出版时间：28 December 2015
• 年：2015
• 卷：220
• 期：part_PA
• 页码：476-483
• 全文大小：901 K

文摘

Since the processing activity of the matrix metalloproteinase MT1-MMP regulates various cellular functions such as motility, invasion, growth, differentiation and apoptosis, precise in vivo evaluation of MT1-MMP activity in cancers can provide beneficial information for both basic and clinical studies. For this purpose, we designed a cleavable Positron Emission Tomography (PET)/optical imaging probe consisting of BODIPY650/665 and polyethylene glycol (PEG) conjugated to opposite ends of MT1-MMP substrate peptides. We used in vitro and in vivo fluorescence experiments to select suitable substrate peptide sequences and PEG sizes for the MT1-MMP probes and obtained an optimized structure referred to here as MBP-2k. Radiofluorinated MBP-2k ([¹⁸F]MBP-2k) was then successfully synthesized via an ¹⁸F–¹⁹F isotopic exchange reaction in BODIPY650/665. After intravenous injection into mice with xenografted tumors, [¹⁸F]MBP-2k showed significantly higher accumulation in HT1080 tumors with high MT1-MMP activity than in A549 tumors that have low MT1-MMP activity. Moreover, PET images showed better contrast in HT1080 tumors. These results show that [¹⁸F]MBP-2k can be used as a hybrid PET/optical imaging agent and is a promising probe for non-invasive monitoring of MT1-MMP activity in cancers. This probe may also efficiently combine targeted tumor imaging with image-guided surgery that could be beneficial for patients in the future.