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首页> 外文期刊>Journal of Controlled Release: Official Journal of the Controlled Release Society >Targeted radiotherapy with tumor vascular homing trimeric GEBP11 peptide evaluated by multimodality imaging for gastric cancer
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Targeted radiotherapy with tumor vascular homing trimeric GEBP11 peptide evaluated by multimodality imaging for gastric cancer

机译：多模态成像评估肿瘤血管归巢三聚体GEBP11肽靶向放射治疗胃癌

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摘要

Targeted radiopharmaceutical is an effective treatment for solid tumors. By labeling with radionuclides, targeting peptide could achieve both noninvasive diagnosis and targeted radionuclide therapy. In order to evaluate the potential applicability of GEBP11 peptides in diagnosis and radiotherapy of gastric cancer, in this study, iodine 131 labeled GEBP11 peptides, including a novel bifid PEGlylated GEBP11 trimer and its corresponding monomer, were developed. The clinical potential of GEBP11 peptides, such as tumor binding affinity and antitumor efficacy was demonstrated and assessed with multimodality imaging methods. Cerenkov and SPECT imaging showed higher tumor uptake for ~(131)I-2PEG-(GEBP11)_3 (P < 0.05, day 1; P < 0.01, day 2; vs. monomer). Biodistribution studies indicated higher tumor accumulation and better T/NT of ~(131)I-2PEG-(GEBP11)_3. Bioluminescence imaging exhibited a significant tumor growth suppression in 131I- 2PEG-(GEBP11)_3 treated group (P < 0.001 vs. control; P < 0.01 vs. monomer). After treatment with ~(131)I-2PEG-(GEBP11)_3, the tumor volume and vasculature decreased significantly, and the survival time was prolonged to 75.5 days. Meanwhile, no significant hepatic or renal toxicity was observed with ~(131)I-2PEG-(GEBP11)_3 administered. In conclusion, ~(131)I-2PEG-(GEBP11)_3 could be a promising candidate for peptide-based targeting therapy of gastric cancer. 2PEG-(GEBP11)_3 might be a potential drug delivery vehicle for the antiangiogenic therapy of gastric cancer.
机译：靶向放射性药物是治疗实体瘤的有效方法。通过用放射性核素标记，靶向肽可以实现无创诊断和靶向放射性核素治疗。为了评估GEBP11肽在胃癌的诊断和放射治疗中的潜在适用性，在这项研究中，开发了碘131标记的GEBP11肽，包括新型的双聚乙二醇化GEBP11三聚体及其相应的单体。用多模态成像方法证实并评估了GEBP11肽的临床潜力，例如肿瘤结合亲和力和抗肿瘤功效。 Cerenkov和SPECT成像显示〜（131）I-2PEG-（GEBP11）_3具有更高的肿瘤摄取率（与单体相比，P <0.05，第1天; P <0.01，第2天）。生物分布研究表明〜（131）I-2PEG-（GEBP11）_3具有更高的肿瘤蓄积性和更好的T / NT。生物发光成像在131I-2PEG-（GEBP11）_3治疗组中显示出显着的肿瘤生长抑制（相对于对照，P <0.001;相对于单体，P <0.01）。用〜（131）I-2PEG-（GEBP11）_3治疗后，肿瘤体积和脉管系统明显减少，存活时间延长至75.5天。同时，施用〜（131）I-2PEG-（GEBP11）_3没有观察到明显的肝或肾毒性。总之，〜（131）I-2PEG-（GEBP11）_3可能是基于肽的胃癌靶向治疗的有希望的候选者。 2PEG-（GEBP11）_3可能是胃癌抗血管生成治疗的潜在药物载体。

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