Yapp Donald T T, Woo Janet, Kartono Aileen, Sy Jonathan, Oliver Thomas, Skov Kirsten A, Koch Cameron J, Adomat Hans, Dragowska Wieslawa H, Fazli Ladan, Ruth Thomas, Adam Michael J, Green David, Gleave Martin
The Department of Advanced Therapeutics, BC Cancer Agency, Vancouver, Canada.
BJU Int. 2007 May;99(5):1154-60. doi: 10.1111/j.1464-410X.2007.06761.x. Epub 2007 Feb 19.
To evaluate hypoxia non-invasively in androgen-dependent (AD), regressing (6-days after castration, RG) and androgen-independent (AI) Shionogi tumours, using the radiolabelled tracer for hypoxia, 18F-EF5, and positron emission tomography (PET).
Groups of mice bearing AD, RG and AI Shionogi tumours were co-injected with 18F-EF5 and unlabelled EF5. The mice were imaged non-invasively with PET to examine the accumulation of 18F-EF5 in hypoxic regions of the tumour. The tumours were subsequently placed in a gamma-counter, or disaggregated for flow cytometry, to determine the levels of 18F-EF5 and the percentage of hypoxic cells present in the tumour, respectively.
The mean (sd) levels of hypoxia in AD Shionogi tumours decreased significantly 6 days after androgen ablation as measured by flow cytometry, from 17.1 (4.77) to 1.74 (0.46)% (P=0.003). There were no significant differences in the levels of 18F-EF5 in the tissue between AD and RG tumours using region-of-interest analysis of PET images or gamma-counting, although the differences were significant when measured by flow cytometry. However, mean (sd) levels of hypoxia in AI Shionogi tumours were significantly higher than in AD tumours regardless of the analysis method; PET, 10.5 (4.93)x10(-5)) Bq/cm2 (P=0.017), flow cytometry, 42.98 (3.35)% (P<0.001), well count, 6.81 (1.17)x10(4) and 13.1 (1.99)x10(4) cpm/g, for AD and AI tumours, respectively (P<0.001).
Differences in hypoxia between AD and AI, but not RG, Shionogi tumours can be detected non-invasively with 18F-EF5 and PET. As prostate tumours are hypoxic and the oxygen levels can change with androgen ablation, noninvasive imaging of hypoxia with PET and 18F-EF5 might ultimately have a prognostic and/or diagnostic role in the clinical management of the disease.
使用放射性标记的缺氧示踪剂18F-EF5和正电子发射断层扫描（PET），对雄激素依赖型（AD）、消退期（去势后6天，RG）和雄激素非依赖型（AI）的小鼠子宫癌肿瘤中的缺氧情况进行无创评估。
将携带AD、RG和AI小鼠子宫癌肿瘤的小鼠分组，同时注射18F-EF5和未标记的EF5。对小鼠进行PET无创成像，以检查肿瘤缺氧区域中18F-EF5的蓄积情况。随后将肿瘤置于γ计数器中，或进行解离以用于流式细胞术分析，分别测定肿瘤中18F-EF5的水平和缺氧细胞的百分比。
通过流式细胞术测定，雄激素去除6天后，AD小鼠子宫癌肿瘤中的平均（标准差）缺氧水平显著降低，从17.1（4.77）%降至1.74（0.46）%（P = 0.003）。使用PET图像的感兴趣区分析或γ计数法时，AD和RG肿瘤组织中18F-EF5的水平无显著差异，尽管通过流式细胞术测量时差异显著。然而，无论采用何种分析方法，AI小鼠子宫癌肿瘤中的平均（标准差）缺氧水平均显著高于AD肿瘤；PET测量结果，AD肿瘤为10.5（4.93）×10(-5) Bq/cm2（P = 0.017），AI肿瘤为42.98（3.35）%（P < 0.001）；γ计数法测量结果，AD肿瘤为6.81（1.17）×10(4) cpm/g，AI肿瘤为13.1（1.99）×10(4) cpm/g（P < 0.001）。
利用18F-EF5和PET可无创检测AD与AI小鼠子宫癌肿瘤之间的缺氧差异，但无法检测AD与RG肿瘤之间的差异。由于前列腺肿瘤存在缺氧情况，且氧水平会随雄激素去除而变化，因此PET和18F-EF5对缺氧进行无创成像最终可能在该疾病的临床管理中具有预后和/或诊断作用。
