Radioimmunolocalization of the monoclonal antibody J28 in early transformation stages in N-nitrosobis(2-hydroxypropyl)amine-induced pancreatic tumors in the Syrian golden hamster

在叙利亚金仓鼠中,N-亚硝基双(2-羟丙基)胺诱导的胰腺肿瘤早期转化阶段单克隆抗体J28的放射免疫定位

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Abstract

We describe the in vivo localization of radiolabeled mAb J28, a murine monoclonal antibody characterizing the oncodevelopmental human fetoacinar pancreatic (FAP) protein, at different stages of chemical induction of pancreatic tumors in the Syrian golden hamster. Before doing localization studies in this model, we looked at the cross-reactivity of mAb J28. Semiquantitative dot-blot analysis demonstrated that the antigen recognized in hamster pancreas has an oncodevelopmental expression pattern, while a molecular mass identical to that of human FAP was deduced from sodium dodecyl sulfate/polyacrylamide gel electrophoresis/nitrocellulose immunoblot. 125I-labeled mAb J28 was administered through micro-osmotic pumps to hamsters treated with N-nitrosobis(2-hydroxypropyl)amine (BHP). This was done at three intervals that roughly correspond to the latent period, pretumoral stages, and terminal cancerogenesis in two independent groups of hamsters. Both studies allowed similar results: (a) mAb J28 accumulated almost specifically in the pancreas; (b) maximal accumulation was associated with pleomorphic alterations of the acinar cell tissue at pretumoral stages; (c) no accumulation was found in the case of adenocarcinoma of the pancreas. It is concluded that FAP behaves as a marker of preneoplastic lesions, and therefore that radioimmunoimaging with mAb J28 might help with early diagnosis of pancreatic cancer.

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