Yingjun Zhi, Rudolf A Werner, Andreas Schirbel, Takahiro Higuchi, Andreas K Buck, Aleksander Kosmala, Thorsten A Bley, Rudolf Hagen, Stephan Hackenberg, Andreas Rosenwald, Agmal Scherzad, Elena Gerhard-Hartmann, Sebastian E Serfling
{"title":"C-X-C基序趋化因子受体4定向PET/CT在新诊断的头颈部鳞状细胞癌中的诊断效果-与[18F]FDG的直接比较。","authors":"Yingjun Zhi, Rudolf A Werner, Andreas Schirbel, Takahiro Higuchi, Andreas K Buck, Aleksander Kosmala, Thorsten A Bley, Rudolf Hagen, Stephan Hackenberg, Andreas Rosenwald, Agmal Scherzad, Elena Gerhard-Hartmann, Sebastian E Serfling","doi":"","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to determine the read-out capabilities of the novel C-X-C motif chemokine receptor 4 (CXCR4)-targeting radiotracer [<sup>68</sup>Ga]Ga-PentixaFor compared to the reference radiotracer [<sup>18</sup>F]FDG in untreated individuals with head and neck squamous cell carcinoma (HNSCC).</p><p><strong>Material and methods: </strong>12 patients with histologically confirmed HNSCC were scheduled for [<sup>18</sup>F]FDG and [<sup>68</sup>Ga]Ga-PentixaFor PET/CT. Maximum standardized uptake values (SUV<sub>max</sub>) and target-to-background ratios (TBR) were applied with vena cava superior serving as reference. In addition, we compared [<sup>68</sup>Ga]Ga-PentixaFor-PET findings with immunohistochemical (IHC) results of CXCR4 expression.</p><p><strong>Results: </strong>On visual assessment, [<sup>18</sup>F]FDG identified more sites of disease, with increased detection rates for both the primary tumor ([<sup>18</sup>F]FDG, 12/12 [100%] vs. [<sup>68</sup>Ga]Ga-PentixaFor, 10/12 [83%]) and LN metastases ([<sup>18</sup>F]FDG, 9/12 [75%] vs. [<sup>68</sup>Ga]Ga-PentixaFor, 8/12 [67%]). Indicative for improved image contrast using [<sup>18</sup>F]FDG, quantification showed a higher TBR for the latter radiotracer, when compared to [<sup>68</sup>Ga]Ga-PentixaFor for all lesions ([<sup>18</sup>F]FDG, 11.7 ± 8.5 vs. [<sup>68</sup>Ga]Ga-PentixaFor, 4.3 ± 1.3; P=0.03), primary tumors ([<sup>18</sup>F]FDG, 13.6 ± 8.7 vs. [<sup>68</sup>Ga]Ga-PentixaFor, 4.4 ± 1.4; P<0.01), and LN lesions ([<sup>18</sup>F]FDG, 9.3 ± 10.6 vs. [<sup>68</sup>Ga]Ga-PentixaFor, 4.7 ± 1.5; P=0.3). IHC showed variable CXCR4 expression in the primary and LN, along with no associations between ex-vivo CXCR4 upregulation and [<sup>68</sup>Ga]Ga-PentixaFor-based TBR (R=0.33, P=0.39) or SUV<sub>max</sub> (R=0.44, P=0.2). Of note, IHC also revealed heterogeneous expression of CXCR4 in immune cells in the tumor microenvironment and in germinal centers, indicative for inflammatory reactions.</p><p><strong>Conclusions: </strong>In HNSCC, [<sup>18</sup>F]FDG demonstrated superior diagnostic performance relative to [<sup>68</sup>Ga]Ga-PentixaFor, in particular for assessment of the primary. Based on the IHC analyses, these findings may be explained by CXCR4 upregulation not only by tumor but also by immune cells in the tumor microenvironment.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":null,"pages":null},"PeriodicalIF":2.0000,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10656626/pdf/","citationCount":"0","resultStr":"{\"title\":\"Diagnostic efficacy of C-X-C motif chemokine receptor 4-directed PET/CT in newly diagnosed head and neck squamous cell carcinoma - a head-to-head comparison with [<sup>18</sup>F]FDG.\",\"authors\":\"Yingjun Zhi, Rudolf A Werner, Andreas Schirbel, Takahiro Higuchi, Andreas K Buck, Aleksander Kosmala, Thorsten A Bley, Rudolf Hagen, Stephan Hackenberg, Andreas Rosenwald, Agmal Scherzad, Elena Gerhard-Hartmann, Sebastian E Serfling\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The aim of this study was to determine the read-out capabilities of the novel C-X-C motif chemokine receptor 4 (CXCR4)-targeting radiotracer [<sup>68</sup>Ga]Ga-PentixaFor compared to the reference radiotracer [<sup>18</sup>F]FDG in untreated individuals with head and neck squamous cell carcinoma (HNSCC).</p><p><strong>Material and methods: </strong>12 patients with histologically confirmed HNSCC were scheduled for [<sup>18</sup>F]FDG and [<sup>68</sup>Ga]Ga-PentixaFor PET/CT. Maximum standardized uptake values (SUV<sub>max</sub>) and target-to-background ratios (TBR) were applied with vena cava superior serving as reference. In addition, we compared [<sup>68</sup>Ga]Ga-PentixaFor-PET findings with immunohistochemical (IHC) results of CXCR4 expression.</p><p><strong>Results: </strong>On visual assessment, [<sup>18</sup>F]FDG identified more sites of disease, with increased detection rates for both the primary tumor ([<sup>18</sup>F]FDG, 12/12 [100%] vs. [<sup>68</sup>Ga]Ga-PentixaFor, 10/12 [83%]) and LN metastases ([<sup>18</sup>F]FDG, 9/12 [75%] vs. [<sup>68</sup>Ga]Ga-PentixaFor, 8/12 [67%]). Indicative for improved image contrast using [<sup>18</sup>F]FDG, quantification showed a higher TBR for the latter radiotracer, when compared to [<sup>68</sup>Ga]Ga-PentixaFor for all lesions ([<sup>18</sup>F]FDG, 11.7 ± 8.5 vs. [<sup>68</sup>Ga]Ga-PentixaFor, 4.3 ± 1.3; P=0.03), primary tumors ([<sup>18</sup>F]FDG, 13.6 ± 8.7 vs. [<sup>68</sup>Ga]Ga-PentixaFor, 4.4 ± 1.4; P<0.01), and LN lesions ([<sup>18</sup>F]FDG, 9.3 ± 10.6 vs. [<sup>68</sup>Ga]Ga-PentixaFor, 4.7 ± 1.5; P=0.3). IHC showed variable CXCR4 expression in the primary and LN, along with no associations between ex-vivo CXCR4 upregulation and [<sup>68</sup>Ga]Ga-PentixaFor-based TBR (R=0.33, P=0.39) or SUV<sub>max</sub> (R=0.44, P=0.2). Of note, IHC also revealed heterogeneous expression of CXCR4 in immune cells in the tumor microenvironment and in germinal centers, indicative for inflammatory reactions.</p><p><strong>Conclusions: </strong>In HNSCC, [<sup>18</sup>F]FDG demonstrated superior diagnostic performance relative to [<sup>68</sup>Ga]Ga-PentixaFor, in particular for assessment of the primary. Based on the IHC analyses, these findings may be explained by CXCR4 upregulation not only by tumor but also by immune cells in the tumor microenvironment.</p>\",\"PeriodicalId\":7572,\"journal\":{\"name\":\"American journal of nuclear medicine and molecular imaging\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2023-10-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10656626/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American journal of nuclear medicine and molecular imaging\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of nuclear medicine and molecular imaging","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
引用次数: 0
摘要
背景:本研究的目的是确定新型C-X-C基序列趋化因子受体4 (CXCR4)靶向放射性示踪剂[68Ga]Ga-PentixaFor与参考放射性示踪剂[18F]FDG在未治疗的头颈部鳞状细胞癌(HNSCC)患者中的读取能力。材料与方法:对12例经组织学证实的HNSCC患者进行[18F]FDG和[68Ga]Ga-PentixaFor PET/CT检查。最大标准摄取值(SUVmax)和目标-背景比(TBR)以上腔静脉为参照。此外,我们比较了[68Ga] ga - pentixa - for - pet结果与CXCR4表达的免疫组化(IHC)结果。结果:在目测方面,[18F]FDG识别出更多的疾病部位,原发肿瘤的检出率([18F]FDG, 12/12 [100%] vs. [68Ga]Ga-PentixaFor, 10/12[83%])和LN转移瘤的检出率([18F]FDG, 9/12 [75%] vs. [68Ga]Ga-PentixaFor, 8/12[67%])均有所增加。定量显示,与[68Ga]Ga-PentixaFor相比,[18F]FDG改善了图像对比度,后一种放射性示踪剂的TBR更高,对于所有病变([18F]FDG, 11.7±8.5比[68Ga]Ga-PentixaFor, 4.3±1.3;P=0.03),原发肿瘤([18F]FDG, 13.6±8.7 vs. [68Ga]Ga-PentixaFor, 4.4±1.4;P18F]FDG, 9.3±10.6 vs. [68Ga]Ga-PentixaFor, 4.7±1.5;P = 0.3)。IHC显示原发性和LN中CXCR4表达变化,体外CXCR4上调与[68Ga] ga - pentixafortbr (R=0.33, P=0.39)或SUVmax (R=0.44, P=0.2)之间无关联。值得注意的是,免疫组化还揭示了CXCR4在肿瘤微环境和生发中心的免疫细胞中的异质表达,表明了炎症反应。结论:在HNSCC中,[18F]FDG相对于[68Ga]Ga-PentixaFor表现出更好的诊断性能,特别是在原发性肿瘤的评估方面。基于免疫组化分析,这些发现可以解释为肿瘤和肿瘤微环境中的免疫细胞中CXCR4的上调。
Diagnostic efficacy of C-X-C motif chemokine receptor 4-directed PET/CT in newly diagnosed head and neck squamous cell carcinoma - a head-to-head comparison with [18F]FDG.
Background: The aim of this study was to determine the read-out capabilities of the novel C-X-C motif chemokine receptor 4 (CXCR4)-targeting radiotracer [68Ga]Ga-PentixaFor compared to the reference radiotracer [18F]FDG in untreated individuals with head and neck squamous cell carcinoma (HNSCC).
Material and methods: 12 patients with histologically confirmed HNSCC were scheduled for [18F]FDG and [68Ga]Ga-PentixaFor PET/CT. Maximum standardized uptake values (SUVmax) and target-to-background ratios (TBR) were applied with vena cava superior serving as reference. In addition, we compared [68Ga]Ga-PentixaFor-PET findings with immunohistochemical (IHC) results of CXCR4 expression.
Results: On visual assessment, [18F]FDG identified more sites of disease, with increased detection rates for both the primary tumor ([18F]FDG, 12/12 [100%] vs. [68Ga]Ga-PentixaFor, 10/12 [83%]) and LN metastases ([18F]FDG, 9/12 [75%] vs. [68Ga]Ga-PentixaFor, 8/12 [67%]). Indicative for improved image contrast using [18F]FDG, quantification showed a higher TBR for the latter radiotracer, when compared to [68Ga]Ga-PentixaFor for all lesions ([18F]FDG, 11.7 ± 8.5 vs. [68Ga]Ga-PentixaFor, 4.3 ± 1.3; P=0.03), primary tumors ([18F]FDG, 13.6 ± 8.7 vs. [68Ga]Ga-PentixaFor, 4.4 ± 1.4; P<0.01), and LN lesions ([18F]FDG, 9.3 ± 10.6 vs. [68Ga]Ga-PentixaFor, 4.7 ± 1.5; P=0.3). IHC showed variable CXCR4 expression in the primary and LN, along with no associations between ex-vivo CXCR4 upregulation and [68Ga]Ga-PentixaFor-based TBR (R=0.33, P=0.39) or SUVmax (R=0.44, P=0.2). Of note, IHC also revealed heterogeneous expression of CXCR4 in immune cells in the tumor microenvironment and in germinal centers, indicative for inflammatory reactions.
Conclusions: In HNSCC, [18F]FDG demonstrated superior diagnostic performance relative to [68Ga]Ga-PentixaFor, in particular for assessment of the primary. Based on the IHC analyses, these findings may be explained by CXCR4 upregulation not only by tumor but also by immune cells in the tumor microenvironment.
期刊介绍:
The scope of AJNMMI encompasses all areas of molecular imaging, including but not limited to: positron emission tomography (PET), single-photon emission computed tomography (SPECT), molecular magnetic resonance imaging, magnetic resonance spectroscopy, optical bioluminescence, optical fluorescence, targeted ultrasound, photoacoustic imaging, etc. AJNMMI welcomes original and review articles on both clinical investigation and preclinical research. Occasionally, special topic issues, short communications, editorials, and invited perspectives will also be published. Manuscripts, including figures and tables, must be original and not under consideration by another journal.