Department of Small Animal Clinical Sciences, Michigan State University, East Lansing, MI 48824, USA.
BMC Cancer. 2013 Apr 30;13:218. doi: 10.1186/1471-2407-13-218.
Human and feline head and neck squamous cell carcinoma (HNSCC) share histology, certain molecular features, as well as locally aggressive and highly recurrent clinical behavior. In human HNSCC, the presence of significant hypoxia within these tumors is considered an important factor in the development of a more aggressive phenotype and poor response to therapy. We hypothesized that feline head and neck tumors, particularly HNSCC, would exhibit hypoxia and that ⁶⁴Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) positron emission tomography/computed tomography (PET/CT) would permit detection of intratumoral hypoxia.
12 cats with measureable head and neck tumors were given ⁶⁴Cu-ATSM and iodinated contrast for PET/CT scan. The presence or absence of hypoxia was also assessed using an intratumoral fluorescent life-time probe to quantitate pO₂ and pimonidazole immunohistochemical staining in biopsy specimens. In two cats, intratumoral O₂ and ⁶⁴Cu-ATSM uptake was measured before and after treatment with anti-angiogenic agents to determine the effect of these agents on hypoxia.
Eleven of twelve feline tumors demonstrated significant ⁶⁴Cu-ATSM uptake, regardless of malignant or benign etiology. The presence (and absence) of hypoxia was confirmed using the fluorescent O₂ detection probe in nine tumors, and using pimonidazole staining in three tumors. Squamous cell carcinomas (HNSCC) demonstrated the highest degree of hypoxia, with Tmax/M ratios ranging from 4.3 to 21.8. Additional non-neoplastic tissues exhibited ⁶⁴Cu-ATSM uptake suggestive of hypoxia including reactive draining lymph nodes, non-malignant thyroid pathology, a tooth root abscess, and otitis media. In two cats with HNSCC that received anti-vascular agents, the pattern of ⁶⁴Cu-ATSM uptake was altered after treatment, demonstrating the potential of the feline model to study the modulation of tumor oxygenation.
Feline HNSCC serves as a clinically relevant model for the investigation of intratumoral hypoxia including its measurement, modulation and targeting.
人类和猫科动物的头颈部鳞状细胞癌（HNSCC）具有相同的组织学、某些分子特征，以及局部侵袭性和高度复发性的临床行为。在人类 HNSCC 中，肿瘤内存在显著的缺氧被认为是发展为侵袭性表型和对治疗反应不良的重要因素。我们假设猫科动物的头颈部肿瘤，特别是 HNSCC，会表现出缺氧，并且 ⁶⁴Cu-二乙酰基双（N4-甲基硫代半卡巴腙）（Cu-ATSM）正电子发射断层扫描/计算机断层扫描（PET/CT）将允许检测肿瘤内缺氧。
12 只可测量的头颈部肿瘤猫接受了 ⁶⁴Cu-ATSM 和碘对比剂进行 PET/CT 扫描。还使用肿瘤内荧光寿命探针来评估缺氧的存在或不存在，以定量评估活检标本中的 pO₂ 和 pimonidazole 免疫组织化学染色。在两只猫中，在使用抗血管生成剂治疗前后测量肿瘤内的 O₂ 和 ⁶⁴Cu-ATSM 摄取，以确定这些药物对缺氧的影响。
12 只猫中的 11 只肿瘤显示出明显的 ⁶⁴Cu-ATSM 摄取，无论其恶性或良性病因如何。在 9 个肿瘤中使用荧光 O₂ 检测探针，在 3 个肿瘤中使用 pimonidazole 染色来确认缺氧的存在（和不存在）。鳞状细胞癌（HNSCC）表现出最高程度的缺氧，Tmax/M 比值范围为 4.3 至 21.8。其他非肿瘤组织也表现出摄取 ⁶⁴Cu-ATSM 的迹象，提示缺氧，包括反应性引流淋巴结、非恶性甲状腺病变、牙根脓肿和中耳炎。在接受抗血管生成剂治疗的两只患有 HNSCC 的猫中，治疗后 ⁶⁴Cu-ATSM 的摄取模式发生改变，证明了这种猫模型在研究肿瘤氧合的调节方面的潜力。
猫科动物的 HNSCC 是研究肿瘤内缺氧的一种临床相关模型，包括其测量、调节和靶向。
