Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
Nucl Med Biol. 2011 Aug;38(6):885-96. doi: 10.1016/j.nucmedbio.2011.02.013. Epub 2011 Apr 21.
Mesothelin is expressed in many cancers, especially in mesothelioma and lung, pancreatic and ovarian cancers. In the present study, we evaluate (111)In labeled antimesothelin antibodies as an imaging bioprobe for the SPECT imaging of mesothelin-expressing tumors.
We radiolabeled the antimesothelin antibodies mAbMB and mAbK1 with (111)In using the p-SCN-bn-DTPA chelator. The immunoreactivity, affinity (K(d)) and internalization properties of the resulting two (111)In labeled antibodies were evaluated in vitro using mesothelin-expressing A431K5 cells. The biodistribution and microSPECT/CT imaging studies with (111)In labeled antibodies were performed in mice bearing both mesothelin positive (A431K5) and mesothelin negative (A431) tumors.
In vitro studies demonstrated that (111)In-mAbMB bound with a higher affinity (K(d)=3.6±1.7 nM) to the mesothelin-expressing A431K5 cells than did the (111)In-mAbK1 (K(d)=29.3±2.3 nM). (111)In-mAbMB was also internalized at a greater rate and extent into the A431K5 cells than was the (111)In-mAbK1. Biodistribution studies showed that (111)In-mAbMB was preferentially localized in A431K5 tumors when compared to A431 tumors. At the low dose, the peak A431K5 tumor uptake of 9.65±2.65% ID/g (injected dose per gram) occurred at 48 h, while at high dose tumor uptake peaked with 14.29±6.18% ID/g at 72 h. Non-specific localization of (111)In-mAbMB was mainly observed in spleen.(111)In-mAbK1 also showed superior localization in A431K5 tumors than in A431 tumors, but the peak uptake was only 3.04±0.68% ID/g at 24 h. MicroSPECT/CT studies confirmed better visualization of A431K5 tumors with (111)In-mAbMB, than with (111)In-mAbK1.
SPECT imaging of mesothelin expressing tumors was demonstrated successfully. Our findings indicate that the antimesothelin antibody mAbMB has the potential to be developed into a diagnostic agent for imaging mesothelin-expressing cancers.
间皮素在许多癌症中表达，特别是间皮瘤、肺癌、胰腺癌和卵巢癌。在本研究中，我们评估了（111）In 标记的抗间皮素抗体作为间皮素表达肿瘤 SPECT 成像的成像生物探针。
我们使用 p-SCN-bn-DTPA 螯合剂标记抗间皮素抗体 mAbMB 和 mAbK1。使用表达间皮素的 A431K5 细胞评估所得两种（111）In 标记抗体的体外免疫反应性、亲和力（Kd）和内化特性。用（111）In 标记抗体进行的生物分布和 microSPECT/CT 成像研究在同时表达间皮素的（A431K5）和不表达间皮素的（A431）肿瘤的小鼠中进行。
体外研究表明，（111）In-mAbMB 与表达间皮素的 A431K5 细胞的结合亲和力（Kd）为 3.6±1.7 nM，高于（111）In-mAbK1（Kd）为 29.3±2.3 nM。（111）In-mAbMB 也以更高的速率和程度内化到 A431K5 细胞中，而（111）In-mAbK1 则不然。生物分布研究表明，与 A431 肿瘤相比，（111）In-mAbMB 优先定位于 A431K5 肿瘤。在低剂量下，48 小时时 A431K5 肿瘤摄取峰值为 9.65±2.65% ID/g（注入剂量/克），而高剂量时肿瘤摄取峰值为 14.29±6.18% ID/g 在 72 小时。（111）In-mAbMB 的非特异性定位主要在脾脏中观察到。（111）In-mAbK1 也显示出在 A431K5 肿瘤中的定位优于 A431 肿瘤，但在 24 小时时仅达到 3.04±0.68% ID/g 的峰值摄取。MicroSPECT/CT 研究证实，（111）In-mAbMB 对 A431K5 肿瘤的可视化效果优于（111）In-mAbK1。
成功地进行了间皮素表达肿瘤的 SPECT 成像。我们的研究结果表明，抗间皮素抗体 mAbMB 有可能被开发为成像间皮素表达癌症的诊断剂。
