Background. CXCR4 is a chemokine receptor that is frequently overexpressed in invasive breast cancer and plays a major role in tumor proliferation, aggressiveness and metastasis. The aim of this prospective study was to establish the value of CXCR4-directed PET imaging in patients with breast cancer using the novel CXCR4-targeted PET probe68Ga-Pentixafor by comparing it with18F-FDG PET/CT (n= 40).Materials and methods. In this prospective cross-sectional study, fifty-one patients with breast cancer aged 36–81 (median (Q1-Q3) 51 (42.5–63)),n= 47 (92%) with initially diagnosed andn= 4 (8%) patients with recurrent breast cancer, underwent CXCR4-targeted PET imaging using68Ga-Pentixafor. Maximum standardized uptake values (SUVmax), total lesion glycolysis (TLG) or total lesion uptake (TLU), metabolic tumor volume (MTV) and tumor-to-background ratios (TBR) of tumor lesions were measured and correlated with pathological prognostic factors, molecular subtypes and CXCR4 immunohistochemistry (IHC) staining.18F-FDG PET/CT images were available in 40 of 51 cases (82%) and were compared semi-quantitatively. The patients were followed up for a median of 11 months (range 4–80 months) to determine whether CXCR4 expression correlated with survival.Results.68Ga-Pentixafor-PET/CT was visually positive in 49/51 (96%) of the cases; in addition, [18F]FDG demonstrated a higher SUVmax compared to68Ga-Pentixafor. The mean SUVmax was 7.26 ± 2.84 and 18.8 ± 9.1 for68Ga-Pentixafor and [18F]FDG, respectively. Thirty-seven percent (18/51) of patients had triple-negative breast cancer and 25/51 (49%) had estrogen receptor (ER+) disease. There was a statistically significant correlation between tumor grade, proliferative index (Ki-67) and SUVmax obtained from68Ga-Pentixafor PETp= 0.002. There was no correlation between the SUVmax obtained from68Ga-Pentixafor and PET molecular subtypes, estrogen receptor (ER), progesterone receptor (PR) or human epidermal growth factor receptor 2 (HER2) status; however, triple-negative breast cancers had more avid68Ga-Pentixafor accumulation compared to luminals A and B. The median (Q1–Q3)68Ga-Pentixafor TLU was significantly higher in HIV-positive (376 (219–881)) compared to HIV-negative (174 (105–557)) breast cancer patients.Conclusions. In conclusion,68Ga-Pentixafor had a sensitivity of 96% and a specificity of 100% for detecting primary breast cancer; in addition,68Ga-Pentixafor exhibited significantly higher uptake in patients with higher tumor grade, high proliferative index and triple-negative breast cancer (TNBC), as well as HIV-infected breast cancer patients, highlighting the potential clinical utility and prognostic role of CXCR4-targeted PET imaging in aggressive breast cancer. Notably,68Ga-Pentixafor complements18F-FDG by detecting more metastasis in the brain and the skull where FDG has limitations, while18F-FDG remains superior for detecting skeletal metastasis. Future research should further explore the potential of CXCR4-targeted PET imaging in selecting patients with triple-negative breast cancer and high-grade breast cancer who may benefit from CXCR4-targeted therapies, particularly in the context of HIV co-infection.
背景：CXCR4是一种趋化因子受体，在侵袭性乳腺癌中常过度表达，并在肿瘤增殖、侵袭和转移中起主要作用。本研究旨在通过比较新型CXCR4靶向PET探针68Ga-Pentixafor与18F-FDG PET/CT（n=40），评估CXCR4导向PET成像在乳腺癌患者中的价值。 材料与方法：在这项前瞻性横断面研究中，51例年龄36-81岁（中位数（Q1-Q3）51（42.5-63））的乳腺癌患者，包括初诊患者47例（92%）和复发患者4例（8%），接受了68Ga-Pentixafor CXCR4靶向PET成像。测量肿瘤病灶的最大标准化摄取值（SUVmax）、总病灶糖酵解（TLG）或总病灶摄取（TLU）、代谢肿瘤体积（MTV）和肿瘤背景比（TBR），并与病理预后因素、分子亚型和CXCR4免疫组化（IHC）染色进行相关性分析。51例中有40例（82%）可获得18F-FDG PET/CT图像，并进行半定量比较。对患者进行了中位11个月（范围4-80个月）的随访，以确定CXCR4表达是否与生存相关。 结果：68Ga-Pentixafor-PET/CT在49/51例（96%）中视觉呈阳性；此外，与68Ga-Pentixafor相比，[18F]FDG显示出更高的SUVmax。68Ga-Pentixafor和[18F]FDG的平均SUVmax分别为7.26 ± 2.84和18.8 ± 9.1。37%（18/51）的患者为三阴性乳腺癌，25/51例（49%）为雌激素受体阳性（ER+）疾病。肿瘤分级、增殖指数（Ki-67）与68Ga-Pentixafor PET获得的SUVmax之间存在统计学显著相关性（p=0.002）。68Ga-Pentixafor PET获得的SUVmax与分子亚型、雌激素受体（ER）、孕激素受体（PR）或人表皮生长因子受体2（HER2）状态无相关性；然而，与Luminal A和B型相比，三阴性乳腺癌的68Ga-Pentixafor摄取更显著。HIV阳性乳腺癌患者的中位（Q1-Q3）68Ga-Pentixafor TLU（376（219-881））显著高于HIV阴性患者（174（105-557））。 结论：总之，68Ga-Pentixafor检测原发性乳腺癌的敏感性为96%，特异性为100%；此外，在肿瘤分级更高、增殖指数更高和三阴性乳腺癌（TNBC）患者以及HIV感染的乳腺癌患者中，68Ga-Pentixafor摄取显著更高，凸显了CXCR4靶向PET成像在侵袭性乳腺癌中的潜在临床效用和预后作用。值得注意的是，68Ga-Pentixafor通过检测FDG有局限性的脑部和颅骨更多转移灶，补充了18F-FDG，而18F-FDG在检测骨转移方面仍更优。未来研究应进一步探索CXCR4靶向PET成像在筛选可能受益于CXCR4靶向治疗的三阴性乳腺癌和高级别乳腺癌患者中的潜力，特别是在HIV合并感染的背景下。
肿瘤(癌症)患者之家