Fjeld J, Brorson B, Martinussen G K, Benestad H, Nustad K
Department of Clinical Chemistry, Rikehospitalet, Oslo, Norway.
Acta Oncol. 1993;32(7-8):873-6. doi: 10.3109/02841869309096149.
The present work demonstrates how intraperitoneal (i.p.) diffusion chambers (DC) can be used to investigate the in vivo stability of the bond between an antibody and its radioactive label. A monoclonal antibody (MoAb) was labelled with 125I or 99mTc. The 125I-labelled preparation showed high stability in vitro, since little radioactivity eluted from incubated DC containing 125I-MoAb bound to specific, fixed target cells. Similarly, when we evaluated the 125I-MoAb in vivo by using the i.p. DC the stability was intact. The 99mTc-MoAb was also stable in vitro, with only about 10% of the radioactivity lost after 48 h. However, when tested in vivo, about 50% of the 99mTc label was lost after 1 day, increasing to 60% after 2 days. Hence, by carrying out preclinical in vivo stability testing with i.p. DC method we discovered that an immunoconjugate with high stability as tested in vitro, in fact was unstable in vivo and probably unsuited for clinical use.
本研究展示了如何利用腹腔内（i.p.）扩散室（DC）来研究抗体与其放射性标记物之间结合的体内稳定性。一种单克隆抗体（MoAb）用125I或99mTc进行标记。125I标记的制剂在体外显示出高稳定性，因为从含有与特异性固定靶细胞结合的125I - MoAb的孵育扩散室中洗脱的放射性很少。同样，当我们通过腹腔内扩散室在体内评估125I - MoAb时，其稳定性良好。99mTc - MoAb在体外也很稳定，48小时后仅有约10%的放射性损失。然而，在体内测试时，99mTc标记物在1天后约有50%丢失，2天后增加到60%。因此，通过腹腔内扩散室方法进行临床前体内稳定性测试，我们发现一种在体外测试具有高稳定性的免疫缀合物，实际上在体内不稳定，可能不适合临床使用。
