Imaging of treatment response to the combination of carboplatin and paclitaxel in human ovarian cancer xenograft tumors in mice using FDG and FLT PET.
Imaging of treatment response to the combination of carboplatin and paclitaxel in human ovarian cancer xenograft tumors in mice using FDG and FLT PET.
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DOI：
10.1371/journal.pone.0085126
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kjær A
中科院分区：
文献类型：
--
作者：
Munk Jensen M;Erichsen KD;Björkling F;Madsen J;Jensen PB;Sehested M;Højgaard L;Kjær A
卡铂和紫杉醇的组合通常用作治疗卵巢癌的一线化疗。因此，在治疗开始后早期使用成像生物标志物来确定治疗敏感性对于从无应答者中识别应答者将是有价值的。在这项研究中，我们描述了使用2-脱氧-2-[18 F]氟-D-葡萄糖（FDG）和3 '-脱氧-3'-[18 F]氟胸苷（FLT）进行葡萄糖摄取和细胞增殖的非侵入性PET成像，用于早期评估卡铂和紫杉醇治疗的人卵巢癌临床前小鼠模型的治疗反应。 在用卡铂和紫杉醇（CaP）治疗之前和治疗开始后第1、4和8天重复测定小鼠（A2780）中人卵巢癌异种移植物中FLT和FDG的体内摄取。使用小动物PET/CT定量示踪剂摄取。将示踪剂摄取与Ki 67、TK 1、GLUT 1、HK 1和HK 2的基因表达进行比较。在第8天，CaP组中的肿瘤显著小于对照组（p=0.03）。在第4天，CaP组的FDG SUVmax比显著低于对照组（105±4% vs 138±9%; p=0.002），在第8天，CaP组的FDG SUVmax比低于对照组（125±13% vs 167±13%; p=0.05）。第1天，CaP组的FLT SUVmax摄取率为89±9%，对照组为109±6%;但差异无统计学显著性（p=0.08）。 我们的数据表明，FDG和FLT PET可用于评估卡铂和紫杉醇联合治疗卵巢癌的抗肿瘤作用。FLT提供早期和短暂的信号，FDG提供较晚和更长时间的反应。这强调了治疗和FLT或FDG成像之间的最佳时机的重要性，因为否则可能会忽略治疗反应。
A combination of carboplatin and paclitaxel is often used as first line chemotherapy for treatment of ovarian cancer. Therefore the use of imaging biomarkers early after initiation of treatment to determine treatment sensitivity would be valuable in order to identify responders from non-responders. In this study we describe the non-invasive PET imaging of glucose uptake and cell proliferation using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and 3’-deoxy-3’-[18F]fluorothymidine (FLT) for early assessment of treatment response in a pre-clinical mouse model of human ovarian cancer treated with carboplatin and paclitaxel. In vivo uptake of FLT and FDG in human ovarian cancer xenografts in mice (A2780) was determined before treatment with carboplatin and paclitaxel (CaP) and repeatedday 1, 4 and 8 after treatment start. Tracer uptake was quantified using small animal PET/CT. Tracer uptake was compared with gene expression of Ki67, TK1, GLUT1, HK1 and HK2. Tumors in the CaP group was significantly smaller than in the control group (p=0.03) on day 8. On day 4 FDG SUVmax ratio was significantly lower in the CaP group compared to the control group (105±4% vs 138±9%; p=0.002) and on day 8 the FDG SUVmax ratio was lower in the CaP compared to the control group (125±13% vs 167±13%; p=0.05). On day 1 the uptake of FLT SUVmax ratio was 89±9% in the CaP group and 109±6% in the control group; however the difference was not statistically significant (p=0.08). Our data suggest that both FDG and FLT PET may be used for the assessment of anti-tumor effects of a combination of carboplatin and paclitaxel in the treatment of ovarian cancer. FLT provides an early and transient signal and FDG a later and more prolonged response. This underscores the importance of optimal timing between treatment and FLT or FDG imaging since treatment response may otherwise be overlooked.
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影响因子：
8.8
作者：
通讯作者：
--
影响因子：
3.7
作者：
Munk Jensen M;Erichsen KD;Björkling F;Madsen J;Jensen PB;Sehested M;Højgaard L;Kjær A
通讯作者：
Kjær A
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影响因子：
3.8
作者：
Jensen MM;Erichsen KD;Johnbeck CB;Björkling F;Madsen J;Jensen PB;Sehested M;Højgaard L;Kjær A
通讯作者：
Kjær A
影响因子：
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通讯作者：
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