Characterization of positron emission tomography hypoxia tracer uptake and tissue oxygenation via electrochemical modeling.
Characterization of positron emission tomography hypoxia tracer uptake and tissue oxygenation via electrochemical modeling.
复制标题
DOI：
10.1016/j.nucmedbio.2011.02.002
复制
发表时间：
2011-08
影响因子：
3.1
通讯作者：
Jeraj R
中科院分区：
文献类型：
--
作者：
Bowen SR;van der Kogel AJ;Nordsmark M;Bentzen SM;Jeraj R
PET缺氧示踪剂独特的摄取和保留机制使它们之间的体内比较具有挑战性。两种常见的低氧放射性示踪剂[61Cu]Cu-ATSM和[18F]FMISO的成像摄取差异通过计算模型来表征，以应对这些挑战。描述这些示踪剂在稳态条件下的生物还原保留机制的电化学公式被用来将时间平均活性浓度与组织偏氧分压(PO2)联系起来，PO2是衡量缺氧的常用指标。根据文献报道的有关反应的自由能变化和还原电位，确定了产物浓度与反应物浓度之比的化学平衡常数。结果示踪剂摄取和PO2之间的转换函数与临床前模型中的实测值进行了比较。此外，根据12例头颈部鳞状细胞癌(HNSCC)患者的铜-ATSM示踪剂活性成像浓度计算的PO2分布与69例HNSCC患者的微电极PO2测量结果进行了验证。铜-ASTM和FMISO模拟的氧分压转换函数在单一偏差可信区间内与临床前实测值一致。在患者群体中模拟的PO2分布和测量的分布之间有很高的相关性(R2=0.94，p<；0.05)。平均而言，微电极缺氧阈值(2.5 mm Hg和5.0 mm Hg)对应于较高的铜-ATSM摄取量(2.5和2.0 SUV)和较低的FMISO摄取量(2.0和1.4 SUV)。1模型中的不确定性主要是由估算的比活度和细胞内酸度的变化决定的。结果表明，铜-ATSM吸收的高动态范围代表了低氧分压的小范围，其值取决于微环境的酸度，而FMISO的吸收代表了与酸度无关的较大范围的PO2值。这些模型阐明了这些差异的可能原因，特别是与图像对比度有关的原因，并可能被证明是量化其他缺氧示踪剂之间关系的有用方法。在治疗前和治疗后对肿瘤缺氧进行全面和可靠的评估可能最好通过多个缺氧标志物的成像来提供，这些标志物提供补充而不是可互换的信息。
Unique uptake and retention mechanisms of PET hypoxia tracers make in vivo comparison between them challenging. Differences in imaged uptake of two common hypoxia radiotracers, [61Cu]Cu-ATSM and [18F]FMISO, were characterized via computational modeling to address these challenges. An electrochemical formalism describing bioreductive retention mechanisms of these tracers under steady-state conditions was adopted to relate time-averaged activity concentration to tissue partial oxygen tension (PO2), a common metric of hypoxia. Chemical equilibrium constants of product concentration to reactant concentration ratios were determined from free energy changes and reduction potentials of pertinent reactions reported in the literature. Resulting transformation functions between tracer uptake and PO2 were compared against measured values in preclinical models. Additionally, calculated PO2 distributions from imaged Cu-ATSM tracer activity concentrations of 12 head and neck squamous cell carcinoma (HNSCC) patients were validated against microelectrode PO2 measurements in 69 HNSCC patients. Both Cu-ASTM and FMISO modeled PO2 transformation functions were in agreement with preclinical measured values within single deviation confidence intervals. High correlation (r2=0.94, p<0.05) was achieved between modeled PO2 distributions and measured distributions in the patient populations. On average, microelectrode hypoxia thresholds (2.5 mmHg and 5.0 mmHg) corresponded to higher Cu-ATSM uptake (2.5 and 2.0 SUV) and lower FMISO uptake (2.0 and 1.4 SUV). Uncertainties in the 1 models were dominated by variations in the estimated specific activity and intracellular acidity. Results indicated that the high dynamic range of Cu-ATSM uptake was representative of a narrow range of low oxygen tension whose values were dependent on microenvironment acidity while FMISO uptake was representative of a wide range of PO2 values that were independent of acidity. The models shed light on possible causes for these discrepancies, particularly as it pertains to image contrast, and may prove to be a useful methodology in quantifying relationships between other hypoxia tracers. Comprehensive and robust assessment of tumor hypoxia prior to as well as in response to therapy may be best-provided by imaging of multiple hypoxia markers that provide complementary rather than interchangeable information.
登录
查看更多内容
DOI：
10.1016/0360-3016(89)90146-6
发表时间：
1989-11-01
影响因子：
7
作者：
RASEY, JS;KOH, WJ;KROHN, KA
通讯作者：
KROHN, KA
某些人类肺癌的组织学结构以及对放射疗法的可能影响。
影响因子：
8.8
作者：
THOMLINSON, R H;GRAY, L H
通讯作者：
GRAY, L H
影响因子：
5.7
作者：
Nordsmark, M;Bentzen, SM;Overgaard, J
通讯作者：
Overgaard, J
DOI：
10.1007/s00259-009-1195-9
发表时间：
2009-10
影响因子：
9.1
作者：
Mees, Gilles;Dierckx, Rudi;Vangestel, Christel;Van de Wiele, Christophe
通讯作者：
Van de Wiele, Christophe
影响因子：
2.6
作者：
Nilsson, J;Lind, BK;Brahme, A
通讯作者：
Brahme, A