Radiopharmaceutical Chemistry, German Cancer Research Center, Heidelberg, Germany.
J Nucl Med. 2013 Aug;54(8):1327-30. doi: 10.2967/jnumed.112.114512. Epub 2013 Jun 26.
The translation of radiolabeled tumor-targeting peptides into clinical routine is often hampered by an enhanced accumulation into the excreting organs. It has recently been reported that the (EH)3 purification tag is able to improve the biodistribution of Affibody molecules. Therefore, the aim of this study was to prove the positive influence of (EH)3 on the biodistribution of 2 peptidic radiopharmaceuticals, Glu-urea-Lys(Ahx)-HBED-CC and TATE-PEG2-HBED-CC (HBED-CC is N,N'-bis [2-hydroxy-5(carboxyethyl)benzyl] ethylenediamine-N,N'- diacetic acid, TATE is octreotate, and PEG2 is 8-amino-3,6-dioxaoctanoic acid spacer).
Both compounds were compared with their respective (EH)3-conjugated variants in cell-based in vitro assays and organ distribution.
The introduction of (EH)3 to HBED-CC significantly changed the biodistribution profiles. In both cases, the uptake in several organs was reduced whereas tumor uptake was not affected. Most importantly, (EH)3 lowered the kidney and liver uptake of the prostate-specific membrane antigen inhibitor each by a factor of 2.8 and, in the case of octreotate, the liver accumulation by a factor of 51.
The biodistribution data suggest that (EH)3 is able to improve the pharmacokinetic properties of peptidic radiopharmaceuticals, leading to reduced uptake in organs such as the liver, an important site of metastatic disease.
放射性标记的肿瘤靶向肽向临床常规的转化通常受到排泄器官中积累增强的阻碍。最近有报道称，(EH)3 纯化标签能够改善 Affibody 分子的生物分布。因此，本研究的目的是证明(EH)3 对 Glu-urea-Lys(Ahx)-HBED-CC 和 TATE-PEG2-HBED-CC 两种肽放射性药物的生物分布的积极影响 (HBED-CC 是 N,N'-双[2-羟基-5(羧乙基)苄基]乙二胺-N,N'-二乙酸，TATE 是奥曲肽，PEG2 是 8-氨基-3,6-二氧代辛酸间隔基)。
在基于细胞的体外测定和器官分布中，将这两种化合物与其各自的(EH)3 缀合变体进行了比较。
(EH)3 的引入显著改变了 HBED-CC 的生物分布谱。在两种情况下，几种器官的摄取减少，而肿瘤摄取不受影响。最重要的是，(EH)3 将前列腺特异性膜抗原抑制剂的肾脏和肝脏摄取分别降低了 2.8 倍，而对于奥曲肽，肝脏的摄取降低了 51 倍。
生物分布数据表明，(EH)3 能够改善肽放射性药物的药代动力学特性，导致肝脏等器官的摄取减少，而肝脏是转移性疾病的重要部位。
