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Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples
PLOS ONE ( IF 2.9 ) Pub Date : 2019-01-15 , DOI: 10.1371/journal.pone.0210905
Clément Morgat , Romain Schollhammer , Gaétan Macgrogan , Nicole Barthe , Valérie Vélasco , Delphine Vimont , Anne-Laure Cazeau , Philippe Fernandez , Elif Hindié

The Gastrin-Releasing Peptide Receptor (GRPR) is over-expressed in estrogen receptor (ER) positive breast tumors and related metastatic lymph nodes offering the opportunity of imaging and therapy of luminal tumors. 68Ga-RM2 binding and 18F-FDG binding in tumoral zones were measured and compared using tissue micro-imaging with a beta imager on 14 breast cancer samples (10 primaries and 4 associated metastatic lymph nodes). Results were then assessed against ER expression, progesterone receptor (PR) expression, HER2 over-expression or not and Ki-67 expression. GRPR immunohistochemistry (IHC) was also performed on all samples. We also retrospectively compared 68Ga-RM2 and 18F-FDG bindings to 18F-FDG SUVmax on the pre-therapeutic PET/CT examination, if available. 68Ga-RM2 binding was significantly higher in tumors expressing GRPR on IHC than in GRPR-negative tumors (P = 0.022). In ER+ tumors, binding of 68Ga-RM2 was significantly higher than 18F-FDG (P = 0.015). In tumors with low Ki-67, 68Ga-RM2 binding was also significantly increased compared to 18F-FDG (P = 0.029). Overall, the binding of 68Ga-RM2 and 18F-FDG displayed an opposite pattern in tumor samples and 68Ga-RM2 binding was significantly higher in tumors that had low 18F-FDG binding (P = 0.021). This inverse correlation was also documented in the few patients in whom a 18F-FDG PET/CT examination before surgery was available. Findings from this in vitro study suggest that GRPR targeting can be an alternative to 18F-FDG imaging in ER+ breast tumors. Moreover, because GRPR antagonists can also be labeled with lutetium-177 this opens new avenues for targeted radionuclide therapy in the subset of patients with progressive metastatic disease following conventional treatments.



中文翻译:

乳腺癌样品中胃泌素释放肽受体(GRP-R)拮抗剂68 Ga-RM2和18 F-FDG结合的比较

胃泌素释放肽受体(GRPR)在雌激素受体(ER)阳性乳腺肿瘤和相关的转移性淋巴结中过表达,从而为管腔肿瘤的成像和治疗提供了机会。测量了肿瘤区域中的68 Ga-RM2结合和18 F-FDG结合,并使用带有β成像仪的组织微成像对14个乳腺癌样品(10个原发灶和4个相关的转移性淋巴结)进行了比较。然后针对ER表达,孕激素受体(PR)表达,HER2过表达与否以及Ki-67表达对结果进行评估。还对所有样品进行了GRPR免疫组织化学(IHC)。我们还回顾性地比较了68 Ga-RM2和18 F-FDG与18 F-FDG SUV的结合马克斯在治疗前PET / CT检查,如果有的话。在IHC上表达GRPR的肿瘤中,68 Ga-RM2的结合显着高于GRPR阴性的肿瘤(P = 0.022)。在ER +肿瘤中,68 Ga-RM2的结合显着高于18 F-FDG(P = 0.015)。与18 F-FDG相比,在Ki-67低的肿瘤中68 Ga-RM2的结合也显着增加(P = 0.029)。总体而言,68 Ga-RM2和18 F-FDG的结合在肿瘤样品和68中显示出相反的模式。在具有低18 F-FDG结合的肿瘤中,Ga-RM2结合显着更高(P = 0.021)。在少数患者术前可进行18 F-FDG PET / CT检查的患者中,也发现了这种负相关关系。这项体外研究的结果表明,在ER +乳腺肿瘤中,GRPR靶向治疗可以替代18 F-FDG成像。此外,因为GRPR拮抗剂也可以用-177标记,这为常规治疗后进行性转移性疾病患者亚组中靶向放射性核素治疗开辟了新途径。

更新日期:2019-01-16
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