Koshida K, Yokoyama K, Uchibayashi T, Yamamoto H, Hirano K, Namiki M
Department of Urology, Kanazawa University, Gifu, Japan.
J Urol. 1997 May;157(5):1941-5.
To investigate factors that influence the imaging of placental alkaline phosphatase (PLAP) producing xenografts using an anti-PLAP monoclonal antibody (MAb).
Three xenografts (human seminoma, HeLa Hep 2 cells, and KK-47 bladder cancer cells) each expressing PLAP to a different degree were used to immunolocalize an anti-PLAP MAb, HPMS-1.
Although the highest PLAP level was found in seminoma xenografts, the MAb was not useful for the imaging of seminoma xenografts because of poor accumulation. Fragmentation of the MAb, such as F(ab)2, however, was shown to be efficient for imaging seminoma xenografts. A distribution study with T1-201 revealed the highest blood flow in HeLa cells and the lowest in seminoma. A difference in blood flow may partially explain the disparity between the amount of MAb accumulation and the level of antigen expression in these three xenografts.
Blood flow in targeted tumors was shown to be more critical than their level of antigen expression for the imaging of xenografts with anti-tumor antibody. In addition, fragmentation of the MAb enabled tumor imaging because of a rapid clearance of the fragment from the circulation.
研究使用抗胎盘碱性磷酸酶(PLAP)单克隆抗体(MAb)对产生PLAP的异种移植瘤进行成像的影响因素。
使用三种不同程度表达PLAP的异种移植瘤(人精原细胞瘤、HeLa Hep 2细胞和KK - 47膀胱癌细胞)对一种抗PLAP单克隆抗体HPMS - 1进行免疫定位。
尽管在精原细胞瘤异种移植瘤中发现了最高水平的PLAP,但由于积累不佳,该单克隆抗体对精原细胞瘤异种移植瘤的成像无用。然而,单克隆抗体的片段,如F(ab)2,被证明对精原细胞瘤异种移植瘤的成像有效。用T1 - 201进行的分布研究显示,HeLa细胞中的血流最高,精原细胞瘤中的血流最低。血流差异可能部分解释了这三种异种移植瘤中MAb积累量与抗原表达水平之间的差异。
对于用抗肿瘤抗体对异种移植瘤进行成像,靶向肿瘤中的血流比其抗原表达水平更为关键。此外,单克隆抗体的片段能够实现肿瘤成像,因为片段能从循环中快速清除。