Garnuszek Piotr, Wiercioch Rafał, Sztajer Helena, Karczmarczyk Urszula, Mirowski Marek
Department of Radiopharmaceuticals, National Institute of Public Health, Warsaw, Poland.
Nucl Med Rev Cent East Eur. 2005;8(1):6-10.
The aim of the study was to examine in vitro and in vivo binding of radiolabelled analogues of P149 peptide by experimental mammary adenocarcinoma with the intention of potential application for diagnosis and internal radiotherapy of tumours.
The 36-amino acid peptide (P149-QY) of 90% homology to 447-480 peptide fragment of hAFP was synthesised and radiolabelled with iodine-125. The biodistribution of P149-Q[125I]-Y was studied in experimental mammary tumours. For in vitro experiments, extract from mouse mammary tumours were prepared and incubated with radioiodinated P149-QY peptide in the presence of a cross-linking reagent.
The gel electrophoresis analysis (SDS-PAGE) showed that radioiodinated P149-QY peptide formed a complex with adenocarcinoma proteins of about 30 kDa. The biodistribution of P149-Q[125I]-Y studied in experimental mammary tumours revealed a higher pharmacokinetic rate in comparison with the whole radioiodinated AFP molecule. A moderate uptake of P149-Q[125I]-Y in the tumour tissue was observed (3.2% ID/g at 30-min p.i.v). However, a faster radioactivity clearance from blood and normal tissues resulted in an increase in the tumour/muscle (T/M) ratio, i.e. from 2.3 to 3.4 after 30 mins and 24 h p.i.v, respectively.
The present study shows that radioiodinated P149-QY peptide reveals some positive features as the AFP receptor radioligand, however, some additional structural modifications of the initial peptide molecule are necessary for full retention of the ligand-receptor interaction of its radiolabelled forms.
本研究旨在检测放射性标记的P149肽类似物在实验性乳腺腺癌中的体外和体内结合情况，以期将其潜在应用于肿瘤的诊断和内放射治疗。
合成了与hAFP的447 - 480肽段具有90%同源性的36个氨基酸的肽段（P149 - QY），并用碘 - 125进行放射性标记。研究了P149 - Q[125I] - Y在实验性乳腺肿瘤中的生物分布。对于体外实验，制备了小鼠乳腺肿瘤提取物，并在交联剂存在的情况下与放射性碘化的P149 - QY肽一起孵育。
凝胶电泳分析（SDS - PAGE）显示，放射性碘化的P149 - QY肽与约30 kDa的腺癌蛋白形成了复合物。在实验性乳腺肿瘤中研究的P149 - Q[125I] - Y的生物分布显示，与整个放射性碘化的AFP分子相比，其药代动力学速率更高。观察到肿瘤组织对P149 - Q[125I] - Y有适度摄取（静脉注射后30分钟时为3.2% ID/g）。然而，血液和正常组织中放射性的更快清除导致肿瘤/肌肉（T/M）比值增加，即静脉注射后30分钟和24小时时分别从2.3增加到3.4。
本研究表明，放射性碘化的P149 - QY肽作为AFP受体放射性配体显示出一些积极特性，然而，为了完全保留其放射性标记形式的配体 - 受体相互作用，初始肽分子需要进行一些额外的结构修饰。
