Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?
Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?
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DOI：
10.1007/s00259-006-0317-x
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发表时间：
2007-07-01
影响因子：
9.1
通讯作者：
Maecke, H.
中科院分区：
文献类型：
--
作者：
Antunes, P.;Ginj, M.;Maecke, H.
镓-68是一种金属正电子发射体，半衰期为68 min，是生长抑素受体阳性肿瘤诊断成像中小分子（如[Ga-68-DOTA，Tyr（3）]奥曲肽）体内应用的理想选择。在临床前研究中，它显示出明显优于In-111标记的同类物。本研究的目的是评估是否第三代生长抑素为基础的，放射性镓标记的肽表现出同样的优越性。通过体外受体放射自显影测定受体亲和力。在AR 4 - 2 J和hsst-HEK转染的细胞系中研究内化速率。结果所有肽段均与hsst 2有较高的亲和力，其中与GaIII复合的肽段亲和力最高。在hsst 3上，情况相反，具有GaIII肽的亲和力降低的趋势。一个显着增加的内化率被发现在SST 2表达细胞的所有Ga-67标记的肽。对于In-111标记的肽，内化到HEK-sst 3中通常更快。没有发现内化到sst 5中。与[In-111-DOTA，1-Nal（3）]奥曲肽和[Ga-67-DOTA，Tyr（3）]奥曲肽相比，采用[Ga-67-DOTA，1-Nal（3）]奥曲肽的生物分布研究显示，在肿瘤和生长抑素受体阳性组织中，两种Ga-67标记肽的受体介导摄取显著更高。一个病人的研究说明了一个广泛的受体亚型档案放射性肽的潜在优势超过一个高亲和力的sst 2-选择性radiopeptide.Conclusion这项研究表明，Ga-67/68-DOTA-八肽显示明显更好的临床前，药理学性能比In-111标记的肽，特别是在sst 2表达细胞和相应的动物模型。它们可能是进一步开发用于临床研究的优秀候选物。
Purpose Gallium-68 is a metallic positron emitter with a half-life of 68 min that is ideal for the in vivo use of small molecules, such as [Ga-68-DOTA, Tyr(3)] octreotide, in the diagnostic imaging of somatostatin receptor-positive tumours. In preclinical studies it has shown a striking superiority over its In-111-labelled congener. The purpose of this study was to evaluate whether third-generation somatostatin-based, radiogallium-labelled peptides show the same superiority.Methods Peptides were synthesised on solid phase. The receptor affinity was determined by in vitro receptor autoradiography. The internalisation rate was studied in AR4-2J and hsst-HEK-transfected cell lines. The pharmacokinetics was studied in a rat xenograft tumour model, AR4-2J.Results All peptides showed high affinities on hsst2, with the highest affinity for the GaIII-complexed peptides. On hsst3 the situation was reversed, with a trend towards lower affinity of the GaIII peptides. A significantly increased internalisation rate was found in sst2-expressing cells for all Ga-67-labelled peptides. Internalisation into HEK-sst3 was usually faster for the In-111-labelled peptides. No internalisation was found into sst5. Biodistribution studies employing [Ga-67-DOTA, 1-Nal(3)] octreotide in comparison to [In-111-DOTA, 1-Nal(3)] octreotide and [Ga-67-DOTA, Tyr(3)] octreotide showed a significantly higher and receptor-mediated uptake of the two Ga-67-labelled peptides in the tumour and somatostatin receptor-positive tissues. A patient study illustrated the potential advantage of a broad receptor subtype profile radiopeptide over a high-affinity sst2-selective radiopeptide.Conclusion This study demonstrates that Ga-67/68-DOTA-octapeptides show distinctly better preclinical, pharmacological performances than the In-111-labelled peptides, especially on sst2-expressing cells and the corresponding animal models. They may be excellent candidates for further development for clinical studies.