Quantitative PET imaging of Met-expressing human cancer xenografts with 89Zr-labelled monoclonal antibody DN30
Quantitative PET imaging of Met-expressing human cancer xenografts with 89Zr-labelled monoclonal antibody DN30
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DOI：
10.1007/s00259-008-0774-5
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发表时间：
2008-10-01
影响因子：
9.1
通讯作者：
van Dongen, Guus A. M. S.
中科院分区：
文献类型：
--
作者：
Perk, Lars R.;Walsum, Marijke Stigter-van;van Dongen, Guus A. M. S.
目的c-Met受体在肿瘤的侵袭和转移过程中起重要作用，因此单克隆抗体靶向c-Met受体是肿瘤诊断和治疗的一种有效方法。正电子发射断层扫描（PET）可能是一个强大的工具，用于指导治疗与抗Met单克隆抗体，如最近描述的单克隆抗体DN 30，因为它允许准确的定量成像肿瘤靶向（免疫PET）。我们考虑了具有Zr-89标记的PET的潜力，（残留放射性核素）或I-124标记材料和方法将共注射的Zr-89-DN 30和碘标记的DN 30的生物分布在携带人胃癌细胞系GLT-16的裸鼠中进行比较，（高Met表达）或头颈癌细胞系FaDu（低Met表达）。在两种异种移植物模型中采集PET图像，直至注射后（p.i.）并用于定量肿瘤吸收。结果GTL-16荷瘤小鼠的生物分布研究表明，Zr-89-DN 30比碘标记的DN 30实现了更高的肿瘤吸收水平（例如，19.6%ID/g vs 5.3%ID/g，注射后5天），而血液水平相似，表明DN 30的内化。因此，选择Zr-89-DN 30用于携带GLT-16的小鼠的PET成像。小至11 mg的肿瘤很容易用免疫PET可视化。与GTL-16异种移植物相比，在FaDu中观察到明显较低的Zr-89摄取（例如7.8%ID/g对18.1%ID/g，注射后3天）。然而，用Zr-89-DN 30免疫PET也清楚地可视化FaDu异种移植物。PET图像衍生的Zr-89肿瘤摄取和离体评估的Zr-89肿瘤摄取之间存在良好的相关性（R-2=0.98）。结论长寿命正电子发射体Zr-89似乎对PET引导的治疗性抗c-Met单克隆抗体的开发具有吸引力。
Purpose Targeting the c-Met receptor with monoclonal antibodies (MAbs) is an appealing approach for cancer diagnosis and treatment because this receptor plays a prominent role in tumour invasion and metastasis. Positron emission tomography (PET) might be a powerful tool for guidance of therapy with anti-Met MAbs like the recently described MAb DN30 because it allows accurate quantitative imaging of tumour targeting (immuno-PET). We considered the potential of PET with either Zr-89-labelled (residualising radionuclide) or I-124-labelled (non-residualising radionuclide) DN30 for imaging of Met-expressing tumours.Materials and methods The biodistribution of co-injected Zr-89-DN30 and iodine-labelled DN30 was compared in nude mice bearing either the human gastric cancer line GLT-16 (high Met expression) or the head-and-neck cancer line FaDu (low Met expression). PET images were acquired in both xenograft models up to 4 days post-injection (p.i.) and used for quantification of tumour uptake.Results Biodistribution studies in GTL-16-tumour-bearing mice revealed that Zr-89-DN30 achieved much higher tumour uptake levels than iodine-labelled DN30 (e.g. 19.6%ID/g vs 5.3%ID/g, 5 days p.i.), while blood levels were similar, indicating internalisation of DN30. Therefore, Zr-89-DN30 was selected for PET imaging of GLT-16-bearing mice. Tumours as small as 11 mg were readily visualised with immuno-PET. A distinctive lower Zr-89 uptake was observed in FaDu compared to GTL-16 xenografts (e.g. 7.8%ID/g vs 18.1%ID/g, 3 days p.i.). Nevertheless, FaDu xenografts were also clearly visualised with Zr-89-DN30 immuno-PET. An excellent correlation was found between PET-image-derived Zr-89 tumour uptake and ex-vivo-assessed Zr-89 tumour uptake (R-2=0.98).Conclusions The long-lived positron emitter Zr-89 seems attractive for PET-guided development of therapeutic anti-c-Met MAbs.