与碘-131或钇-90标记的MOv18相比，镥-177标记的MOv18在根除表达α叶酸受体的肿瘤异种移植方面具有更好的治疗效果。

(177)Lu- labeled MOv18 as compared to (131)I- or (90)Y-labeled MOv18 has the better therapeutic effect in eradication of alpha folate receptor-expressing tumor xenografts.

作者信息

Zacchetti Alberto, Coliva Angela, Luison Elena, Seregni Ettore, Bombardieri Emilio, Giussani Augusto, Figini Mariangela, Canevari Silvana

机构信息

Unit of Molecular Therapies, Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy.

出版信息

Nucl Med Biol. 2009 Oct;36(7):759-70. doi: 10.1016/j.nucmedbio.2009.05.004. Epub 2009 Jul 29.

DOI:10.1016/j.nucmedbio.2009.05.004

PMID:19720288

Abstract

INTRODUCTION

The mouse monoclonal antibody MOv18, directed against the alpha-isoform of folate receptor (FR), was investigated to identify the optimal radioconjugate for radioimmunotherapy of minimal residual disease in ovarian cancer.

METHODS

Pharmacokinetics, biodistribution, long-term therapeutic efficacy and toxicity of MOv18, labeled with the beta-emitters (131)I, (90)Y and (177)Lu, were compared in a xenografted mouse model, composed by two cell lines, A431FR and A431MK, differing only for FR expression.

RESULTS

A shorter blood clearance and a higher tumor uptake were observed for (90)Y- and (177)Lu- compared to (131)I-MOv18, and a shorter blood pharmacokinetics was recorded in A431FR-bearing animals. At equitoxic maximum tolerable doses, the general irradiation by (131)I- and (90)Y-MOv18 gives rise to strong targeted effects on A431FR and nontargeted effects on A431MK tumors, while (177)Lu-MOv18 was able to eradicate small size tumor masses expressing the antigen of interest exerting only mild non-targeted effects.

CONCLUSION

(177)Lu-MOv18 at the maximal tolerated dose is the immunoradioconjugate with the best therapeutic window in experimental conditions of small tumor volume.

摘要

引言

研究了针对叶酸受体（FR）α异构体的小鼠单克隆抗体MOv18，以确定用于卵巢癌微小残留病放射免疫治疗的最佳放射性缀合物。

方法

在由两种仅在FR表达上不同的细胞系A431FR和A431MK组成的异种移植小鼠模型中，比较了用β发射体（131）I、（90）Y和（177）Lu标记的MOv18的药代动力学、生物分布、长期治疗效果和毒性。

结果

与（131）I-MOv18相比，观察到（90）Y-和（177）Lu-MOv18的血液清除时间更短，肿瘤摄取更高，并且在携带A431FR的动物中记录到血液药代动力学更短。在等毒性最大耐受剂量下，（131）I-和（90）Y-MOv18的全身照射对A431FR产生强烈的靶向作用，对A431MK肿瘤产生非靶向作用，而（177）Lu-MOv18能够根除表达感兴趣抗原的小尺寸肿瘤块，仅产生轻微的非靶向作用。