[18F]FLT PET for non-invasive assessment of tumor sensitivity to chemotherapy: studies with experimental chemotherapy TP202377 in human cancer xenografts in mice.

[18F]FLT PET for non-invasive assessment of tumor sensitivity to chemotherapy: studies with experimental chemotherapy TP202377 in human cancer xenografts in mice.
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DOI:
10.1371/journal.pone.0050618
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Kjær A
Kjær A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Munk Jensen M;Erichsen KD;Björkling F;Madsen J;Jensen PB;Sehested M;Højgaard L;Kjær A

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3′-脱氧-3 ′-[18 F]氟胸苷([18 F]FLT)是一种用于评估体内细胞增殖的示踪剂。该研究的目的是使用[18F]FLT正电子发射断层扫描(PET)来研究实验性化疗剂TP 202377在敏感和耐药肿瘤中的非侵入性早期抗增殖作用。使用来自3种人癌细胞系的小鼠中的异种移植物:TP 202377敏感性A2780卵巢癌细胞系(n = 8-16个肿瘤/组)、诱导抗性A2780/Top216细胞系(n = 8-12个肿瘤/组)和天然抗性SW 620结肠癌细胞系(n = 10个肿瘤/组)。      在基线时以及TP 202377给药(40 mg/kg i. v.)后6小时、第1天和第6天重复研究[18 F]FLT的体内摄取。被发起。使用小动物PET/CT定量示踪剂摄取。与对照组相比,TP 202377(40 mg/kg,0小时)在第6天对敏感的A2780肿瘤模型产生生长抑制(P<0.001)。在A2780肿瘤模型中,与基线摄取相比,TP 202377给药导致给药开始后6小时(-46%; P<0.001)和第1天(-44%; P<0.001)的[18 F]FLT摄取显著降低。第6天的摄取与基线相当。在耐药A2780/Top216和SW 620肿瘤模型中,TP 202377给药未影响肿瘤生长或[18 F]FLT摄取。在所有对照组中,[18 F]FLT的摄取量均未发生变化。Ki 67基因表达抑制[18F]FLT摄取。用TP 202377(单次静脉给药)处理小鼠A2780异种移植物导致6小时后通过[18 F]FLT PET评估的细胞增殖显著降低。抑制在第1天持续存在;然而,细胞增殖在第6天恢复至基线。在耐药A2780/Top216和SW 620肿瘤模型中,给药后[18 F]FLT的摄取没有变化。使用[18 F]FLT PET,在治疗开始后6小时就可以无创性地区分敏感和耐药肿瘤。
3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) is a tracer used to assess cell proliferation in vivo. The aim of the study was to use [18F]FLT positron emission tomography (PET) to study non-invasively early anti-proliferative effects of the experimental chemotherapeutic agent TP202377 in both sensitive and resistant tumors. Xenografts in mice from 3 human cancer cell lines were used: the TP202377 sensitive A2780 ovary cancer cell line (n = 8–16 tumors/group), the induced resistant A2780/Top216 cell line (n = 8–12 tumors/group) and the natural resistant SW620 colon cancer cell line (n = 10 tumors/group). In vivo uptake of [18F]FLT was studied at baseline and repeated 6 hours, Day 1, and Day 6 after TP202377 treatment (40 mg/kg i.v.) was initiated. Tracer uptake was quantified using small animal PET/CT. TP202377 (40 mg/kg at 0 hours) caused growth inhibition at Day 6 in the sensitive A2780 tumor model compared to the control group (P<0.001). In the A2780 tumor model TP202377 treatment caused significant decrease in uptake of [18F]FLT at 6 hours (-46%; P<0.001) and Day 1 (-44%; P<0.001) after treatment start compared to baseline uptake. At Day 6 uptake was comparable to baseline. Treatment with TP202377 did not influence tumor growth or [18F]FLT uptake in the resistant A2780/Top216 and SW620 tumor models. In all control groups uptake of [18F]FLT did not change. Ki67 gene expression paralleled [18F]FLT uptake. Treatment of A2780 xenografts in mice with TP202377 (single dose i.v.) caused a significant decrease in cell proliferation assessed by [18F]FLT PET after 6 hours. Inhibition persisted at Day 1; however, cell proliferation had returned to baseline at Day 6. In the resistant A2780/Top216 and SW620 tumor models uptake of [18F]FLT did not change after treatment. With [18F]FLT PET it was possible to distinguish non-invasively between sensitive and resistant tumors already 6 hours after treatment initiation.
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期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
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Shah C;Miller TW;Wyatt SK;McKinley ET;Olivares MG;Sanchez V;Nolting DD;Buck JR;Zhao P;Ansari MS;Baldwin RM;Gore JC;Schiff R;Arteaga CL;Manning HC
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