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Abstract：
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is common, and its incidence is increasing, particularly in HIV-infected individuals who present with more aggressive disease. Despite aggressive treatment, the prognosis remains poor because of resistance to chemoradiation therapy. So far, studies report very low [68Ga]Ga-Pentixafor avidity in HNSCC. This study investigated the diagnostic performance of CXCR4-directed imaging of carcinoma of the oral cavity, oropharynx, and nasopharynx with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine ligand [68Ga]Ga-Pentixafor and explored its ability to quantify CXCR4 expression in vivo.
METHODS: In this prospective cross-sectional study, twenty-three (23) patients aged 52.9 ± 10.4 (19.6), 17 males and 6 females with primarily diagnosed (n = 17) or pre-treated (n = 6) SCC of the oral cavity (OCSCC, n = 11), oropharynx (OPSCC, n = 9), nasopharynx (NPSCC, n = 2) and unknown primary (n = 1) underwent imaging with [68Ga]Ga-Pentixafor-PET/CT. In 16/23 patients 2-[18F]fluoro-2-deoxy-D-glucose ([18F]F-FDG) served as a standard reference. All lesions were visually rated using a 5-point Likert scale. For both tracers, maximum standardized uptake values (SUVmax) and the total lesion uptake (TLU) were recorded and compared using the Wilcox-signed rank test. In addition, the tumor-to-background ratios were derived using the liver (TLR), spleen (TSR), and posterior cervical muscles (TMR) as background. The relationships between the SUVs of the two tracers were assessed using the Spearman correlation. CXCR4 immunohistochemistry (IHC) staining was correlated with 68Ga-Pentixafor-PET/CT in 21/23 patients.
RESULTS: Ninety-one percent (21/23) of tumors were visually detected on [68Ga]Ga-Pentixafor; however, [68Ga]Ga-Pentixafor was less intense compared with [18F]F-FDG-PET. Quantitative analysis showed higher [18F]F-FDG SUVmax in comparison with [68Ga]Ga-Pentixafor (16 ± 6.7 vs. 5.8 ± 2.6 g/mL, p = 0.011) and SUVmean (9.3 ± 4.1 vs. 3± 1.6 g/mL, p < 0.001) and TBR 4.9 ± 2.3 vs. 2.36 ± 1.4 p = 0.014. Nasopharyngeal cancer demonstrated more intense tracer accumulation than oropharyngeal and oral cavity malignancies. CXCR4 IHC staining was positive in 15/21 patients, and there was a statistically significant correlation between IHC staining and [68Ga]Ga-Pentixafor SUVmean r = 0.5 p = 0.027, and performance status r = 0.83 p = 0.0104.
CONCLUSIONS: In conclusion, although [68Ga]Ga-Pentixafor cannot replace [18F]F-FDG as a diagnostic tool because of its lower avidity, the correlation between CXCR4 targeted 68Ga-Pentixafor PET imaging and CXCR4 IHC staining indicates the potential of 68Ga-Pentixafor as an effective tool for selecting patients who may benefit from therapies targeting CXCR4. In addition, [68Ga]Ga-Pentixafor has no physiological brown fat uptake, which often obscures cervical lesions on [18F]F-FDG PET/CT imaging.
METHODS: In this prospective cross-sectional study, twenty-three (23) patients aged 52.9 ± 10.4 (19.6), 17 males and 6 females with primarily diagnosed (n = 17) or pre-treated (n = 6) SCC of the oral cavity (OCSCC, n = 11), oropharynx (OPSCC, n = 9), nasopharynx (NPSCC, n = 2) and unknown primary (n = 1) underwent imaging with [68Ga]Ga-Pentixafor-PET/CT. In 16/23 patients 2-[18F]fluoro-2-deoxy-D-glucose ([18F]F-FDG) served as a standard reference. All lesions were visually rated using a 5-point Likert scale. For both tracers, maximum standardized uptake values (SUVmax) and the total lesion uptake (TLU) were recorded and compared using the Wilcox-signed rank test. In addition, the tumor-to-background ratios were derived using the liver (TLR), spleen (TSR), and posterior cervical muscles (TMR) as background. The relationships between the SUVs of the two tracers were assessed using the Spearman correlation. CXCR4 immunohistochemistry (IHC) staining was correlated with 68Ga-Pentixafor-PET/CT in 21/23 patients.
RESULTS: Ninety-one percent (21/23) of tumors were visually detected on [68Ga]Ga-Pentixafor; however, [68Ga]Ga-Pentixafor was less intense compared with [18F]F-FDG-PET. Quantitative analysis showed higher [18F]F-FDG SUVmax in comparison with [68Ga]Ga-Pentixafor (16 ± 6.7 vs. 5.8 ± 2.6 g/mL, p = 0.011) and SUVmean (9.3 ± 4.1 vs. 3± 1.6 g/mL, p < 0.001) and TBR 4.9 ± 2.3 vs. 2.36 ± 1.4 p = 0.014. Nasopharyngeal cancer demonstrated more intense tracer accumulation than oropharyngeal and oral cavity malignancies. CXCR4 IHC staining was positive in 15/21 patients, and there was a statistically significant correlation between IHC staining and [68Ga]Ga-Pentixafor SUVmean r = 0.5 p = 0.027, and performance status r = 0.83 p = 0.0104.
CONCLUSIONS: In conclusion, although [68Ga]Ga-Pentixafor cannot replace [18F]F-FDG as a diagnostic tool because of its lower avidity, the correlation between CXCR4 targeted 68Ga-Pentixafor PET imaging and CXCR4 IHC staining indicates the potential of 68Ga-Pentixafor as an effective tool for selecting patients who may benefit from therapies targeting CXCR4. In addition, [68Ga]Ga-Pentixafor has no physiological brown fat uptake, which often obscures cervical lesions on [18F]F-FDG PET/CT imaging.
摘要：
背景：头颈部鳞状细胞癌（HNSCC）很常见，它的发病率在增加，特别是在艾滋病毒感染的个体谁表现出更积极的疾病。尽管积极治疗，由于对放化疗的耐药性，预后仍然较差。到目前为止,研究报告HNSCC中[68Ga]Ga-Pentixa的亲和力非常低。这项研究调查了CXCR4定向成像对口腔癌的诊断性能，口咽,使用放射性标记的趋化因子配体[68Ga]Ga-Pentixafor进行正电子发射断层扫描/计算机断层扫描（PET/CT）的鼻咽，并探索了其在体内量化CXCR4表达的能力。
方法：在这项前瞻性横断面研究中，23名患者，年龄52.9±10.4（19.6），17名男性和6名女性，主要诊断（n=17）或治疗前（n=6）口腔SCC（OCSCC，n=11),口咽（OPSCC，n=9),鼻咽（NPSCC，n=2）和未知的原发性（n=1）使用[68Ga]Ga-Pentixafor-PET/CT进行了成像。在16/23患者中，2-[18F]氟-2-脱氧-D-葡萄糖（[18F]F-FDG）用作标准参考。使用5点Likert量表对所有病变进行视觉评估。对于两个示踪剂，使用Wilcox符号秩检验记录并比较最大标准化摄取值(SUVmax)和总病变摄取(TLU).此外,肿瘤背景比使用肝脏（TLR），脾脏(TSR),和颈后肌（TMR）作为背景。使用Spearman相关性评估了两种示踪剂的SUV之间的关系。在21/23例患者中，CXCR4免疫组织化学（IHC）染色与68Ga-Pentixafor-PET/CT相关。
结果：在[68Ga]Ga-Pentixafor上目视检测到百分之九十一（21/23）的肿瘤；然而，[68Ga]Ga-Pentixafor与[18F]F-FDG-PET相比强度较低。定量分析显示，与[68Ga]Ga-Pentixafor相比，[18F]F-FDGSUVmax更高（16±6.7vs.5.8±2.6g/mL，p=0.011）和SUVmean（9.3±4.1vs.3±1.6g/mL，p<0.001）和TBR4.9±2.3vs.2.36±1.4p=0.014。鼻咽癌表现出比口咽和口腔恶性肿瘤更强烈的示踪剂积累。15/21例患者CXCR4IHC染色阳性，IHC染色与[68Ga]Ga-Pentixa之间的SUVmeanr=0.5p=0.027，性能状态r=0.83p=0.0104之间存在统计学上的显着相关性。
结论：结论：虽然[68Ga]Ga-Pentixafor不能取代[18F]F-FDG作为诊断工具，因为它的亲和力较低，CXCR4靶向68Ga-PentixaforPET成像和CXCR4IHC染色之间的相关性表明68Ga-Pentixafor作为选择可能受益于CXCR4靶向治疗的患者的有效工具的潜力.此外,[68Ga]Ga-Pentixafor没有生理棕色脂肪摄取，通常在[18F]F-FDGPET/CT成像上掩盖宫颈病变。
方法：在这项前瞻性横断面研究中，23名患者，年龄52.9±10.4（19.6），17名男性和6名女性，主要诊断（n=17）或治疗前（n=6）口腔SCC（OCSCC，n=11),口咽（OPSCC，n=9),鼻咽（NPSCC，n=2）和未知的原发性（n=1）使用[68Ga]Ga-Pentixafor-PET/CT进行了成像。在16/23患者中，2-[18F]氟-2-脱氧-D-葡萄糖（[18F]F-FDG）用作标准参考。使用5点Likert量表对所有病变进行视觉评估。对于两个示踪剂，使用Wilcox符号秩检验记录并比较最大标准化摄取值(SUVmax)和总病变摄取(TLU).此外,肿瘤背景比使用肝脏（TLR），脾脏(TSR),和颈后肌（TMR）作为背景。使用Spearman相关性评估了两种示踪剂的SUV之间的关系。在21/23例患者中，CXCR4免疫组织化学（IHC）染色与68Ga-Pentixafor-PET/CT相关。
结果：在[68Ga]Ga-Pentixafor上目视检测到百分之九十一（21/23）的肿瘤；然而，[68Ga]Ga-Pentixafor与[18F]F-FDG-PET相比强度较低。定量分析显示，与[68Ga]Ga-Pentixafor相比，[18F]F-FDGSUVmax更高（16±6.7vs.5.8±2.6g/mL，p=0.011）和SUVmean（9.3±4.1vs.3±1.6g/mL，p<0.001）和TBR4.9±2.3vs.2.36±1.4p=0.014。鼻咽癌表现出比口咽和口腔恶性肿瘤更强烈的示踪剂积累。15/21例患者CXCR4IHC染色阳性，IHC染色与[68Ga]Ga-Pentixa之间的SUVmeanr=0.5p=0.027，性能状态r=0.83p=0.0104之间存在统计学上的显着相关性。
结论：结论：虽然[68Ga]Ga-Pentixafor不能取代[18F]F-FDG作为诊断工具，因为它的亲和力较低，CXCR4靶向68Ga-PentixaforPET成像和CXCR4IHC染色之间的相关性表明68Ga-Pentixafor作为选择可能受益于CXCR4靶向治疗的患者的有效工具的潜力.此外,[68Ga]Ga-Pentixafor没有生理棕色脂肪摄取，通常在[18F]F-FDGPET/CT成像上掩盖宫颈病变。
