pH-Responsive Polymers for Improving the Signal-to-Noise Ratio of Hypoxia PET Imaging with [18 F]Fluoromisonidazole.,Macromolecular Rapid Communications

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pH-Responsive Polymers for Improving the Signal-to-Noise Ratio of Hypoxia PET Imaging with [18 F]Fluoromisonidazole.
Macromolecular Rapid Communications ( IF 4.2 ) Pub Date : 2020-04-06 , DOI: 10.1002/marc.202000061
Jeroen A C M Goos ₁ , Maria Davydova ₂ , Nigel Lengkeek ₃ , Ivan Greguric ₃ , Michael R Whittaker ₄ , John F Quinn ₄ , Jonathan B Baell ₅ , Jason S Lewis ₂ , Thomas P Davis ₄

Affiliation

To improve the signal‐to‐noise ratio of hypoxia positron emission tomography (PET) imaging, stimuli‐responsive polymers are designed for the delivery of the hypoxia PET tracer fluorine‐18 labeled fluoromisonidazole ([¹⁸F]FMISO). Linear poly(N ‐(2‐(hydroxypropyl)methacrylamide)) polymers are functionalized with hydrazide linkers that form pH‐sensitive acyl hydrazone bonds after their conjugation to an [¹⁸F]FMISO ketone analogue. The release of the [¹⁸F]FMISO ketone analogue from the polymers is considerably faster at a lower pH and its uptake is significantly higher in cancer cells growing under acidic conditions. Additionally, the retention of the PET tracer is significantly higher in hypoxic cells compared to normoxic cells. The delivery of a PET tracer using stimuli‐responsive polymers may be an attractive strategy to improve signal‐to‐noise ratios in PET imaging.

中文翻译：

使用 [18 F] 氟咪唑改善缺氧 PET 成像的信噪比的 pH 响应聚合物。

为了提高缺氧正电子发射断层扫描 (PET) 成像的信噪比，设计了刺激响应聚合物来输送缺氧 PET 示踪剂氟-18 标记的氟咪唑 ([ ¹⁸ F] FMISO)。线性聚（N-（2-（羟丙基）甲基丙烯酰胺））聚合物用酰肼连接物功能化，在与[ ¹⁸ F]FMISO 酮类似物缀合后形成对pH敏感的酰基腙键。[ ¹⁸F] 来自聚合物的 FMISO 酮类似物在较低的 pH 值下明显更快，并且在酸性条件下生长的癌细胞中其吸收明显更高。此外，与常氧细胞相比，低氧细胞中 PET 示踪剂的保留率明显更高。使用刺激响应聚合物传递 PET 示踪剂可能是提高 PET 成像信噪比的有吸引力的策略。

更新日期：2020-04-06

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