Section of Nuclear Medicine, Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):554-60. doi: 10.1016/j.ijrobp.2010.11.007. Epub 2011 Jan 13.
A growing body of in vitro evidence links alterations of the intermediary metabolism in cancer to treatment outcome. This study aimed to characterize tumor oxidative metabolism and perfusion in vivo using dynamic positron emission tomography (PET) with 1- [(11)C]-acetate (ACE) during radiotherapy.
Nine patients with head-and-neck cancer were studied. Oxidative metabolic rate (k(mono)) and perfusion (rF) of the primary tumors were assessed by dynamic ACE-PET at baseline and after 15, 30, and 55 Gy was delivered. Tumor glucose uptake (Tglu) was evaluated with [(18)F]-fluorodeoxyglucose PET at baseline. Patients were grouped into complete (CR, n = 6) and partial responders (PR, n = 3) to radiotherapy.
The 3 PR patients died within a median follow-up period of 33 months. Baseline k(mono) was almost twice as high in CR as in PR (p = 0.02) and Tglu was lower in CR than in PR (p = 0.04). k(mono) increased during radiotherapy in PR (p = 0.004) but remained unchanged in CR. There were no differences in rF between CR and PR at any dosage. k(mono) and rF were coupled in CR (p = 0.001), but not in PR.
This study shows that radiosensitive tumors might rely predominantly on oxidative metabolism for their bioenergetic needs. The impairment of oxidative metabolism in radioresistant tumors is potentially reversible, suggesting that therapies targeting the intermediary metabolism might improve treatment outcome.
越来越多的体外证据表明,癌症中间代谢的改变与治疗结果有关。本研究旨在使用 1- [(11)C]-乙酸盐(ACE)通过动态正电子发射断层扫描(PET)来描述肿瘤的氧化代谢和灌注在放射治疗过程中的变化。
研究了 9 例头颈部癌症患者。在基线和接受 15、30 和 55 Gy 照射后,通过动态 ACE-PET 评估原发性肿瘤的氧化代谢率(k(mono))和灌注(rF)。在基线时使用 [(18)F]-氟脱氧葡萄糖 PET 评估肿瘤葡萄糖摄取(Tglu)。根据放射治疗的反应将患者分为完全缓解(CR,n = 6)和部分缓解(PR,n = 3)。
3 例 PR 患者在中位随访 33 个月内死亡。CR 的基线 k(mono)几乎是 PR 的两倍(p = 0.02),CR 的 Tglu 低于 PR(p = 0.04)。PR 患者在放射治疗过程中 k(mono)增加(p = 0.004),但 CR 患者则保持不变。在任何剂量下,CR 和 PR 之间 rF 没有差异。CR 中 k(mono)和 rF 相关(p = 0.001),但 PR 中则不相关。
本研究表明,对放疗敏感的肿瘤可能主要依赖氧化代谢来满足其生物能量需求。在放射抵抗肿瘤中氧化代谢的损伤是潜在可逆转的,这表明针对中间代谢的治疗方法可能会改善治疗结果。