Kinne R W, Schemer K, Behr T, Sharkey R M, Palombokinne E, Emmrich F, Goldenberg D M, Wolf F, Becker W
Institute of Clinical Immunology and Transfusion Medicine, University of Leipzig, Germany.
Nucl Med Commun. 1999 Jan;20(1):67-75. doi: 10.1097/00006231-199901000-00011.
In a comparative study, the in vivo metabolic profile of 99Tcm-anti-CD4 monoclonal antibodies (MAb) and Fab' fragments (direct thiol-reduction method) was investigated in rats with adjuvant arthritis. Plasma samples were obtained 1, 4 and 15 h following intravenous injection and urine was collected over 15 h. The composition of the radiolabelled molecules was analysed by gel filtration chromatography. The profile of the complete MAb was as follows. (1) Serum: a predominant peak of 150 kDa (complete MAb; approximately 80%); three minor peaks of 125, 100 and 50 kDa (presumably H2L1, H2 and H1 chains; 14%); and two small peaks of approximately 1500 and 300 Da (presumably 99Tcm-glutathione and Cys-99Tcm-Cys; 5%). (2) Urine: minor peaks of 125, 100 and 50 kDa (15%), major peaks of 1500 and 300 Da (50%), and an additional 25-kDa peak (30%). The profile of the Fab' was as follows. (1) Serum: three minor peaks of 150 kDa [conceivably F(ab')2 plus soluble-CD4], 110 kDa [F(ab')2] and 95 kDa (Fab' plus soluble-CD4; together 30%); a predominant peak of 55 kDa (Fab'; 61%); and two minor peaks of 1500 and 300 Da (8%). (2) Urine: predominantly a 55 kDa (16%) and 1500 and 300 Da peaks (74%). Also, the anti-CD4 Fab' showed higher urine excretion and lower plasma levels than the complete anti-CD4 MAb, but still more favourable tissue-to-blood ratios following scintigraphy of the arthritic joints. Thus, the complex metabolic profile of the anti-CD4 Fab' does not appear to interfere with specific targeting of the inflamed synovial membrane.
在一项对比研究中，研究了99锝标记的抗CD4单克隆抗体（MAb）和Fab'片段（直接巯基还原法）在佐剂性关节炎大鼠体内的代谢情况。静脉注射后1、4和15小时采集血浆样本，并在15小时内收集尿液。通过凝胶过滤色谱法分析放射性标记分子的组成。完整单克隆抗体的情况如下：（1）血清：一个主要峰为150 kDa（完整单克隆抗体；约80%）；三个较小峰分别为125、100和50 kDa（可能是H2L1、H2和H1链；14%）；以及两个约1500和300 Da的小峰（可能是99锝-谷胱甘肽和半胱氨酸-99锝-半胱氨酸；5%）。（2）尿液：125、100和50 kDa的较小峰（15%），1500和300 Da的主要峰（50%），以及一个额外的25 kDa峰（30%）。Fab'片段的情况如下：（1）血清：150 kDa的三个较小峰[可能是F(ab')2加可溶性CD4]、110 kDa[F(ab')2]和95 kDa（Fab'加可溶性CD4；共30%）；一个主要峰为55 kDa（Fab'；61%）；以及两个1500和300 Da的较小峰（8%）。（2）尿液：主要是一个55 kDa峰（16%）和1500和300 Da峰（74%）。此外，抗CD4 Fab'片段的尿液排泄量高于完整的抗CD4单克隆抗体，血浆水平低于完整抗体，但在关节炎关节闪烁扫描后组织与血液的比值仍更有利。因此，抗CD4 Fab'片段复杂的代谢情况似乎并未干扰炎症滑膜的特异性靶向。
