Hadebe Bawinile, Harry Lerwine, Gabela Lerato, Masikane Siphelele, Patel Maryam, Zwane Sizwe, Pillay Venesen, Bipath Presha, Cebekhulu Nonhlanhla, Nyakale Nozipho, Ramdass Prathima, Msimang Mpumelelo, Aldous Colleen, Sathekge Mike, Vorster Mariza
Department of Nuclear Medicine, College of Health Sciences, University of KwaZulu Natal, Private Bag X54001, Durban 4001, South Africa.
Inkosi Albert Luthuli Central Hospital, Durban 4001, South Africa.
Diagnostics (Basel). 2024 Jun 28;14(13):1375. doi: 10.3390/diagnostics14131375.
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 [Ga]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 [Ga]Ga-Pentixafor and explored its ability to quantify CXCR4 expression in vivo.
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 ( = 17) or pre-treated ( = 6) SCC of the oral cavity (OCSCC, = 11), oropharynx (OPSCC, = 9), nasopharynx (NPSCC, = 2) and unknown primary ( = 1) underwent imaging with [Ga]Ga-Pentixafor-PET/CT. In 16/23 patients 2-[18F]fluoro-2-deoxy-D-glucose ([F]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 Ga-Pentixafor-PET/CT in 21/23 patients.
Ninety-one percent (21/23) of tumors were visually detected on [Ga]Ga-Pentixafor; however, [Ga]Ga-Pentixafor was less intense compared with [F]F-FDG-PET. Quantitative analysis showed higher [F]F-FDG SUVmax in comparison with [Ga]Ga-Pentixafor (16 ± 6.7 vs. 5.8 ± 2.6 g/mL, 0.011) and SUVmean (9.3 ± 4.1 vs. 3± 1.6 g/mL, 0.001) and TBR 4.9 ± 2.3 vs. 2.36 ± 1.4 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 [Ga]Ga-Pentixafor SUVmean r = 0.5 = 0.027, and performance status r = 0.83 = 0.0104.
In conclusion, although [Ga]Ga-Pentixafor cannot replace [F]F-FDG as a diagnostic tool because of its lower avidity, the correlation between CXCR4 targeted Ga-Pentixafor PET imaging and CXCR4 IHC staining indicates the potential of Ga-Pentixafor as an effective tool for selecting patients who may benefit from therapies targeting CXCR4. In addition, [Ga]Ga-Pentixafor has no physiological brown fat uptake, which often obscures cervical lesions on [F]F-FDG PET/CT imaging.
头颈部鳞状细胞癌（HNSCC）很常见，且其发病率正在上升，尤其是在感染HIV且疾病侵袭性更强的个体中。尽管进行了积极治疗，但由于对放化疗产生耐药性，预后仍然很差。到目前为止，研究报告显示[镓]Ga-喷替沙氟在HNSCC中的亲和力非常低。本研究使用放射性标记的趋化因子配体[镓]Ga-喷替沙氟，通过正电子发射断层扫描/计算机断层扫描（PET/CT）研究了CXCR4导向成像在口腔、口咽和鼻咽癌中的诊断性能，并探讨了其在体内定量CXCR4表达的能力。
在这项前瞻性横断面研究中，23例年龄为52.9±10.4（19.6）岁的患者（17例男性和6例女性），主要为初诊（n = 17）或经治疗（n = 6）的口腔鳞状细胞癌（OCSCC，n = 11）、口咽鳞状细胞癌（OPSCC，n = 9）、鼻咽鳞状细胞癌（NPSCC，n = 2）和原发灶不明（n = 1）的患者接受了[镓]Ga-喷替沙氟-PET/CT成像。在23例患者中的16例中，2-[18F]氟-2-脱氧-D-葡萄糖（[F]F-FDG）用作标准对照。所有病变均使用5分李克特量表进行视觉评分。对于两种示踪剂，记录最大标准化摄取值（SUVmax）和总病变摄取量（TLU），并使用Wilcox符号秩检验进行比较。此外，使用肝脏（TLR）、脾脏（TSR）和颈后肌肉（TMR）作为背景得出肿瘤与背景比值。使用Spearman相关性评估两种示踪剂SUV之间的关系。在23例患者中的21例中，CXCR4免疫组织化学（IHC）染色与镓-喷替沙氟-PET/CT相关。
91%（21/23）的肿瘤在[镓]Ga-喷替沙氟上可被视觉检测到；然而，与[F]F-FDG-PET相比，[镓]Ga-喷替沙氟的强度较低。定量分析显示，与[镓]Ga-喷替沙氟相比，[F]F-FDG的SUVmax更高（16±6.7 vs. 5.8±2.6 g/mL，P = 0.011）和SUVmean更高（9.3±4.1 vs. 3±1.6 g/mL，P = 0.001）以及TBR更高（4.9±2.3 vs. 2.36±1.4，P = 0.014）。鼻咽癌显示出比口咽和口腔恶性肿瘤更强的示踪剂积聚。CXCR4 IHC染色在21例患者中的15例中呈阳性，IHC染色与[镓]Ga-喷替沙氟SUVmean之间存在统计学显著相关性（r = 0.5，P = 0.027），与体能状态之间也存在相关性（r = 0.83，P = 0.0104）。
总之，尽管由于[镓]Ga-喷替沙氟的亲和力较低，其不能替代[F]F-FDG作为诊断工具，但CXCR4靶向的镓-喷替沙氟PET成像与CXCR4 IHC染色之间的相关性表明，镓-喷替沙氟有潜力作为一种有效的工具，用于选择可能从靶向CXCR4的治疗中获益的患者。此外，[镓]Ga-喷替沙氟没有生理性棕色脂肪摄取，而这在[F]F-FDG PET/CT成像中常常会掩盖颈部病变。
