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铟 - 111标记的抗人高分子量黑色素瘤相关抗原单克隆抗体的免疫反应性和生物分布

Immunoreactivity and biodistribution of indium-111-labeled monoclonal antibody to a human high molecular weight-melanoma associated antigen.

作者信息

Fawwaz R A, Wang T S, Estabrook A, Rosen J M, Hardy M A, Alderson P O, Srivastava S C, Richards P, Ferrone S

出版信息

J Nucl Med. 1985 May;26(5):488-92.

PMID:3989605
Abstract

The anti-human, high molecular weight-melanoma associated antigen (HMW-MAA) MoAb 225.28S was chelated with 111In and then tested for its in vitro reactivity with cultured human melanoma cells and for its biodistribution in human melanoma bearing nude mice. In vitro studies showed that the radiolabeled antibody reacted specifically with cultured melanoma cells. However, binding of DTPA to the monoclonal antibody reduced its titer with cultured melanoma cells from 1:1024 to 1:512. Further labeling of the DTPA-antibody conjugate with 111In caused an additional reduction of its titer to 1:128. Injection of the radiolabeled monoclonal antibody into nude mice resulted in the accumulation of significantly (p less than 0.001) higher radioactivity in melanoma tissue than in nude mice injected with either [111In] chloride or 111In-labeled antibody to human acid phosphatase. The specificity of the distribution of the radiolabeled antibody in nude mice also was indicated by its poor localization in lesions other than melanoma (e.g., human prostate carcinoma and chronic abscess). The localization of antibody in liver and kidney was also high, although lower than that achieved in tumor. These results indicate that 111In-labeled monoclonal antibodies to human tumor associated antigens may be useful for localizing malignant lesions. However, there is a need to improve labeling and/or purification of antibody in order to decrease renal and hepatic activity.

摘要

将抗人高分子量黑色素瘤相关抗原(HMW - MAA)单克隆抗体225.28S与铟 - 111(111In)螯合,然后检测其与培养的人黑色素瘤细胞的体外反应性以及在荷人黑色素瘤裸鼠体内的生物分布。体外研究表明,放射性标记的抗体与培养的黑色素瘤细胞发生特异性反应。然而,二乙三胺五乙酸(DTPA)与单克隆抗体结合后,其与培养的黑色素瘤细胞的效价从1:1024降至1:512。用111In对DTPA - 抗体偶联物进行进一步标记导致其效价进一步降至1:128。将放射性标记的单克隆抗体注射到裸鼠体内后,黑色素瘤组织中积累的放射性明显高于注射氯化铟([111In] chloride)或111In标记的抗人酸性磷酸酶抗体的裸鼠(p < 0.001)。放射性标记抗体在裸鼠体内分布的特异性还体现在其在黑色素瘤以外的病变(如人前列腺癌和慢性脓肿)中的定位较差。抗体在肝脏和肾脏中的定位也较高,尽管低于在肿瘤中的定位。这些结果表明,111In标记的抗人肿瘤相关抗原单克隆抗体可能有助于定位恶性病变。然而,需要改进抗体的标记和/或纯化以降低肾脏和肝脏的放射性活性。

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