Hertel A, Baum R P, Auerbach B, Herrmann A, Hör G
Abteilung Nuklearmedizin, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt/Main, BR Deutschland.
Nuklearmedizin. 1990 Nov;29(5):221-7.
Murine monoclonal antibodies (MAb) are applied on a growing scale in radioimmunoscintigraphy (IS) for diagnostic and therapeutic purposes. This increasing use of xenogeneic substances in rapidly growing numbers of patients raises questions of accuracy and reliability of the MAb and also the problem of potential human immunoreaction (human anti-mouse IgG antibodies--HAMA). The aim of this study was to evaluate the clinical relevance of HAMA following IS regarding allergic complications and in vivo effects on IS after repeated applications of MAbs. Out of over 800 immunoscintigraphic examinations performed during the last 5 years in our department 289 studies (in 190 patients) with up to 10 applications (13 different MAbs all together) were considered. Only 1 patient with a high HAMA titer developed a mild allergic reaction (local urticaria) after the 3rd application of an anti-CEA MAb. In 171 intensively documented serum courses following IS, 50 (29%) showed elevated HAMA [1st application: 25/108 (23%); 2nd application: 20/41 (49%): 3rd application: 5/11 (45%); 4th-10th application: no HAMA/11 (2 anti-CEA, 9 Antimyosin)]. Only with strongly increased HAMA values (five times the value before 1st application) there was an altered biodistribution of the MAbs in IS with partially inhibited (8/25 studies with repeated applications) tumor localization. Some patients still demonstrated positive tumor localization despite a HAMA reaction. The problem of HAMA in the diagnostic work-up using MAbs is not the allergic reaction but the potential effects on IS in repeated studies. HAMA should be measured prior to repeated immunoscintigraphic studies.
鼠单克隆抗体(MAb)越来越广泛地应用于放射免疫闪烁显像(IS),用于诊断和治疗目的。在越来越多的患者中使用异源物质,这引发了关于MAb准确性和可靠性的问题,以及潜在的人体免疫反应问题(人抗鼠IgG抗体——HAMA)。本研究的目的是评估IS后HAMA在过敏性并发症方面的临床相关性,以及重复应用MAb后对IS的体内影响。在过去5年我们科室进行的800多次免疫闪烁显像检查中,有289项研究(涉及190名患者)使用了多达10次(共13种不同的MAb)。只有1名HAMA滴度高的患者在第3次应用抗CEA MAb后出现了轻度过敏反应(局部荨麻疹)。在171项IS后详细记录的血清检测过程中,50项(29%)显示HAMA升高[第1次应用:25/108(23%);第2次应用:20/41(49%);第3次应用:5/11(45%);第4 - 10次应用:11项中无HAMA(2项抗CEA,9项抗肌球蛋白)]。只有当HAMA值大幅升高(是第1次应用前值的5倍)时,IS中MAb的生物分布才会改变,肿瘤定位部分受到抑制(重复应用的25项研究中有8项)。尽管有HAMA反应,一些患者的肿瘤定位仍呈阳性。在使用MAb的诊断检查中,HAMA的问题不是过敏反应,而是重复研究中对IS的潜在影响。在重复进行免疫闪烁显像研究之前,应检测HAMA。