PET and MRI of metastatic peritoneal and pulmonary colorectal cancer in mice with human epidermal growth factor receptor 1-targeted 89Zr-labeled panitumumab.
PET and MRI of metastatic peritoneal and pulmonary colorectal cancer in mice with human epidermal growth factor receptor 1-targeted 89Zr-labeled panitumumab.
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DOI：
10.2967/jnumed.111.094169
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Brechbiel MW
中科院分区：
文献类型：
--
作者：
Nayak TK;Garmestani K;Milenic DE;Brechbiel MW
人表皮生长因子受体（HER 1）在结直肠癌（CRC）的发病机制中起重要作用。帕尼单抗是一种获批用于CRC的抗HER 1单克隆抗体。然而，关于相应远处转移灶中的HER 1状态的数据很少，关于帕尼单抗在原发性和转移性病灶中的定位的信息也很少。本研究介绍了使用89 Zr-帕尼单抗的PET和MRI在使用不同转移模型评估远处转移瘤中HER 1状态的效用。在表达HER 1的LS-174 T和HER 1阴性A375肿瘤异种移植物中进行了体内生物分布和PET研究。此外，在不同的腹膜内和肺转移模型中进行了研究。对转移模型进行MRI研究，以表征89 Zr-帕尼单抗在不同病变部位的靶向潜力。在所有HER 1表达模型中均实现了HER 1介导的靶向。LS-174 T肿瘤曲线下面积（AUC）是A375的AUC的3.7倍。LS-174 T肿瘤AUC为204.13 ± 9.67，显著高于（p < 0.001）共注射0.1 mg帕尼单抗阻断靶点的小鼠获得的LS-174 T肿瘤AUC 36.45 ± 1.39。两种模型腹腔给药后的肿瘤摄取量存在差异，肿瘤负荷3 d组的肿瘤摄取量是肿瘤负荷7 d组的2倍以上。PET和MRI研究显示，在所有转移模型中，HER 1介导的肿瘤靶向。然而，在不同的LS 174 T肿瘤模型之间观察到显著差异。对于皮下肿瘤模型，在注射后3-4天观察到约40%ID/g的峰值肿瘤摄取，而对于胸部肿瘤，在注射后2天观察到约75%ID/g，对于腹膜内肿瘤，在注射后1-2天观察到约95%ID/g。本研究证明了89 Zr-帕尼单抗在评估远处转移瘤的HER 1状态和了解不同病变部位抗体摄取变化方面的潜在效用。89 Zr-帕尼单抗在患者分层和免疫治疗中起着至关重要的作用，因此需要进一步研究临床转化。
Human Epidermal growth factor receptor (HER1) plays an important role in the pathogenesis of colorectal cancer (CRC). Panitumumab is an anti-HER1 monoclonal antibody approved for use in CRC. However, little data exists regarding HER1 status in the corresponding distant metastases and corresponding little information is available regarding the localization of panitumumab at primary and metastatic lesions. The utility of PET and MRI using 89Zr-panitumumab to assess the status of HER1 in distant metastases using different metastases models is presented in this study. In vivo biodistribution and PET studies were performed in HER1-expressing LS-174T and HER1-negative A375 tumor xenografts. Additionally, studies were performed in different models of intraperitoneal and pulmonary metastases. MRI studies were performed for metastatic models to characterize the targeting potential of 89Zr-panitumumab at different lesion sites. HER1-mediated targeting was achieved in all HER1-expressing models. The LS-174T tumor area under the curve (AUC)was 3.7-fold greater than the AUC for A375. The LS-174T tumor AUC of 204.13 ± 9.67 was significantly greater ( p < 0.001) than LS-174T tumor AUC of 36.45 ± 1.39 obtained from mice coinjected with 0.1 mg panitumumab for blocking the target. Differences were observed in two models of intraperitoneal models; tumor uptake in mice with 3 d tumor burden group was more than 2-fold greater than the mice with 7 d tumor burden. PET and MRI studies revealed HER1-mediated tumor targeting in all metastatic models. However, significant differences were observed between different LS174T tumor models. Peak tumor uptake of approximately 40 % ID/g was observed at 3–4 d after injection for the subcutaneous tumor model in contrast to approximately 75 % ID/g at 2 d after injection for the thoracic tumors and approximately 95 % ID/g at 1–2 d after injection for the intraperitoneal tumors. The potential utility of 89Zr-panitumumab in assessing HER1 status in distant metastases and understanding the variations in antibody uptake at different lesion sites is demonstrated in this study. 89Zr-panitumumab can play a vital role in patient stratification and immunotherapy and therefore warrants further investigation for clinical translation.
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影响因子：
3.7
作者：
Nayak TK;Garmestani K;Milenic DE;Baidoo KE;Brechbiel MW
通讯作者：
Brechbiel MW
影响因子：
2.3
作者：
Hebbar, Mohamed;Wacrenier, Agnes;Pruvot, Francois-Rene
通讯作者：
Pruvot, Francois-Rene
DOI：
10.2967/jnumed.109.061820
发表时间：
2009-07
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Niu G;Li Z;Xie J;Le QT;Chen X
通讯作者：
Chen X
影响因子：
2.9
作者：
MEARES, CF;MCCALL, MJ;MCTIGUE, M
通讯作者：
MCTIGUE, M
DOI：
10.2967/jnumed.109.071290
发表时间：
2010-06
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Nayak TK;Garmestani K;Baidoo KE;Milenic DE;Brechbiel MW
通讯作者：
Brechbiel MW