Halpern S E, Hagan P L, Chen A, Birdwell C R, Bartholomew R M, Burnett K G, David G S, Poggenburg K, Merchant B, Carlo D J
Veterans Administration Medical Center, San Diego, CA 92161.
J Nucl Med. 1988 Oct;29(10):1688-96.
The distribution and kinetics of six human and one murine monoclonal IgM antibodies (MoAb) were studied in BALB/c mice. Labeling was with 111In, 75Se, and 125I. The monomers and pentamers of certain MoAbs were studied. Human distribution studies were also performed. The serum containing [111In]MoAb was obtained from one of the patients 24 hr after administration and injected into mice which were then killed and assayed for 111In distribution. In general, the [75Se] and [111In]MoAbs had distribution and kinetic patterns that were similar while the 125I-labeled MoAbs dehalogenated after 4 hr. Monomers and pentamers had highly similar distributions suggesting that the distribution of IgMs may be based on factors other than molecular size. The murine IgM showed a somewhat different distribution in mice than did human IgMs. Serum from the patient containing [111In]MoAb had a distribution in mice similar to that of the patient with high liver and gastrointestinal uptake. The human imaging indicates that it is possible to target tumor with human IgM MoAbs, but significant problems remain in regard to their clinical use.
在BALB/c小鼠中研究了六种人源和一种鼠源单克隆IgM抗体(MoAb)的分布和动力学。用111In、75Se和125I进行标记。研究了某些MoAb的单体和五聚体。还进行了人体分布研究。给药24小时后从一名患者获得含[111In]MoAb的血清,注入小鼠体内,然后处死小鼠并检测111In的分布。一般来说,[75Se]和[111In]MoAb具有相似的分布和动力学模式,而125I标记的MoAb在4小时后发生脱卤反应。单体和五聚体具有高度相似的分布,这表明IgM的分布可能基于分子大小以外的因素。鼠源IgM在小鼠体内的分布与人源IgM略有不同。含[111In]MoAb的患者血清在小鼠体内的分布与肝脏和胃肠道摄取较高的患者相似。人体成像表明,用人源IgM MoAb靶向肿瘤是可能的,但在其临床应用方面仍存在重大问题。