18F-Fluoroglucosylation of peptides, exemplified on cyclo(RGDfK)
18F-Fluoroglucosylation of peptides, exemplified on cyclo(RGDfK)
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DOI：
10.1007/s00259-009-1122-0
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发表时间：
2009-09-01
影响因子：
9.1
通讯作者：
Wester, Hans-Juergen
中科院分区：
文献类型：
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作者：
Hultsch, Christina;Schottelius, Margret;Wester, Hans-Juergen
氨氧基功能化肽和 F-18 标记醛之间的肟形成最近被引入，作为一种快速一步化学选择性合成放射性氟化肽的强大方法。在这里，使用氨氧基乙酰基缀合的环状 RGD 肽研究了使用常规生产且易于获得的 [F-18] 氟脱氧葡萄糖 ([F-18]FDG) 作为醛基辅基的潜力（环（RGDfK（Aoa-（Boc）））作为模型肽。使用含有过量d-葡萄糖的常规生产（[F-18]FDGTUM）中的[F-18]FDG不允许以合理的产率放射合成活性> 37 MBq的[F-18]FDG-RGD，从而可以直接使用临床级[F-18]FDG进行F-18标记肽的常规临床合成然而，使用不添加载体（n.c.a.）的[F-18]FDG，通过从过量葡萄糖中分离[F-18]FDGTUM，可得到[F-18]FDG-RGD，其产率为56-93%（经过衰减校正），活性高达37 MBq。合适的反应条件为在120°C和pH 2.5下反应20分钟，肽浓度为5 mM。在 M21 黑色素瘤裸鼠的初步体内生物分布研究中，与“金标准”[F-18]galacto-RGD 相比，[F-18]FDG-RGD 显示肿瘤积累增加（注射后 120 分钟分别为 2.18 % iD/g 和 1.49 %iD/g），但非靶器官的摄取也略有增加，导致两种化合物的肿瘤/器官比率相当。这些数据表明使用 n.c.a. 对氨氧基功能化肽进行化学选择性 F-18 标记代表了一种放射性氟化/糖基化策略，可在与 Aoa 肽反应之前以适当的药代动力学制备高产率的 F-18 标记肽。 [F-18]FDG 合成、肽的[F-18]氟葡萄糖基化可能是目前使用的化学选择性一步 F-18 标记方案的一种有前景的替代方案。
Oxime formation between an aminooxy-functionalized peptide and an F-18-labelled aldehyde has recently been introduced as a powerful method for the rapid one-step chemoselective synthesis of radiofluorinated peptides.Here, the potential of using routinely produced and thus readily available [F-18]fluorodeoxyglucose ([F-18]FDG) as the aldehydic prosthetic group was investigated using an aminooxyacetyl-conjugated cyclic RGD peptide (cyclo(RGDfK(Aoa-(Boc)) as a model peptide.The use of [F-18]FDG from routine production ([F-18]FDGTUM) containing an excess of d-glucose did not allow the radiosynthesis of [F-18]FDG-RGD in activities > 37 MBq in reasonable yield, rendering the direct use of clinical grade [F-18]FDG for the routine clinical synthesis of F-18-labelled peptides impossible. Using no-carrier-added (n.c.a.) [F-18]FDG obtained via HPLC separation of [F-18]FDGTUM from excess glucose, however, afforded [F-18]FDG-RGD in yields of 56-93% (decay corrected) and activities up to 37 MBq. Suitable reaction conditions were 20 min at 120A degrees C and pH 2.5, and a peptide concentration of 5 mM. In a preliminary in vivo biodistribution study in M21 melanoma-bearing nude mice, [F-18]FDG-RGD showed increased tumour accumulation compared to the "gold standard" [F-18]galacto-RGD (2.18 vs 1.49 %iD/g, respectively, at 120 min after injection), but also slightly increased uptake in non-target organs, leading to comparable tumour/organ ratios for both compounds.These data demonstrate that chemoselective F-18-labelling of aminooxy-functionalized peptides using n.c.a. [F-18]FDG represents a radiofluorination/glycosylation strategy that allows preparation of F-18-labelled peptides in high yield with suitable pharmacokinetics. As soon as the necessary n.c.a. preparation of [F-18]FDG prior to reaction with the Aoa-peptide can be implemented in a fully automated [F-18]FDG-synthesis, [F-18]fluoroglucosylation of peptides may represent a promising alternative to currently used chemoselective one-step F-18-labelling protocols.