PET measurements of myocardial glucose metabolism with 1-11C-glucose and kinetic modeling
PET measurements of myocardial glucose metabolism with 1-11C-glucose and kinetic modeling
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DOI：
10.2967/jnumed.106.037598
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发表时间：
2007-06-01
影响因子：
9.3
通讯作者：
Gropler, Robert J.
中科院分区：
文献类型：
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作者：
Herrero, Pilar;Kisrieva-Ware, Zulfia;Gropler, Robert J.
本研究的目的是探讨1-C-11-葡萄糖PET动力学的房室模型是否可以用于心肌葡萄糖代谢的非侵入性测量，而不是最初的提取。方法：22只杂种犬在多种代谢状态下同时注射1-C-11-葡萄糖和U-(13)C葡萄糖，然后进行1h的PET数据采集。心脏组织标本分析C-13-糖原含量(nmoL/g)。测定动脉血和冠状静脉窦血(ART/CS)中葡萄糖(MU/L)、C-11-葡萄糖、(CO2)-C-11和C-11-总酸性代谢物(C-11-乳酸[LA]+(CO2)-C-11)(计数/分钟/毫升)，并计算心肌(A)葡萄糖和1-C-11-葡萄糖萃取物的分数、EF(GLU)和EF(C-11-GLU)；(B)C-11-GLU和C-11-LA氧化，((11)C-GLU)和((11)C-LA)；(C)C-11-糖酵解，GCF(C-11-GLU)；和(D)C-11-糖原含量，GNF(C-11-GLU)。在此基础上，建立了一个考虑外源性C-11-LA对心肌C-11活性贡献的房室模型(M)，用来测量M-EF(GLU)、M-GCF(GLU)、M-OF(GLU)、M-GNF(GLU)，以及以糖原形式储存的心肌葡萄糖比例M-GNF(GLU)/M-EF(GLU)。结果：ART/CS数据显示：(1)EF(C-11-Glu)与EF(Glu)有很强的相关性(r=0.92，P<0.0001；斜率=0.95，P=1)。(2)在高糖提取和氧化干预中，(C-11-GLU)对总氧化的贡献高于(C-11-LA)(P<；0.01)。相反，在葡萄糖摄取和氧化被抑制的干预中，(C-11-LA)高于(C-11-GLU)(P<；0.05)。(3)GnF(C-11-Glu)/EF(Glu)与直接测定C-13-糖原含量之间有很强的相关性(r=0.96P<；0.0001)。M-EF(Glu)、M-Gcf(Glu)和M-of(Glu)分别与EF(Glu)(斜率=0.92r=0.95P<；0.0001)、GCF(斜率=0.79，r=0.97P<；0.0001)和(C-11-Glu)(斜率=0.70r=0.96P<；0.0001)显著相关。M-GnF(Glu)/M-EF(Glu)与C-13含量显著相关(r=0.92P<；0.0001)。结论：在非缺血条件下，用1-C-11-葡萄糖和考虑二次标记外源性C-11-乳酸摄取和氧化的隔室模拟方法，可以无创地测量心肌的葡萄糖代谢。
The aim of this study was to investigate whether compartmental modeling of 1-C-11-glucose PET kinetics can be used for noninvasive measurements of myocardial glucose metabolism beyond its initial extraction. Methods: 1-C-11-Glucose and U-(13)Cglucose were injected simultaneously into 22 mongrel dogs under a wide range of metabolic states; this was followed by 1 h of PET data acquisition. Heart tissue samples were analyzed for C-13-glycogen content (nmol/g). Arterial and coronary sinus blood samples (ART/CS) were analyzed for glucose (mu mol/mL), C-11-glucose, (CO2)-C-11, and C-11-total acidic metabolites (C-11-lactate [LA] + (CO2)-C-11) (counts/min/mL) and were used to calculate myocardial fractions of (a) glucose and 1-C-11-glucose extractions, EF(GLU) and EF(C-11-GLU); (b) C-11-GLU and C-11-LA oxidation, OF((11) C-GLU) and OF((11) C-LA); (c) C-11-glycolsysis, GCF(C-11-GLU); and (d) C-11-glycogen content, GNF(C-11-GLU). On the basis of these measurements, a compartmental model (M) that accounts for the contribution of exogenous C-11-LA to myocardial C-11 activity was implemented to measure M-EF(GLU), M-GCF(GLU), M-OF(GLU), M-GNF(GLU), and the fraction of myocardial glucose stored as glycogen M-GNF(GLU)/M-EF(GLU)). Results: ART/CS data showed the following: (a) A strong correlation was found between EF(C-11-GLU) and EF(GLU) (r = 0.92, P < 0.0001; slope = 0.95, P = not significantly different from 1). (b) In interventions with high glucose extraction and oxidation, the contribution of OF(C-11-GLU) to total oxidation was higher than that of OF(C-11-LA) (P < 0.01). In contrast, in interventions in which glucose uptake and oxidation were inhibited, OF(C-11-LA) was higher than OF(C-11-GLU) (P < 0.05). (c) A strong correlation was found between GNF(C-11-GLU)/EF(GLU) and direct measurements of fractional C-13-glycogen content, (r = 0.96, P < 0.0001). Model-derived PET measurements of M-EF(GLU), M-GCF(GLU), and M-OF(GLU) strongly correlated with EF(GLU) (slope = 0.92, r = 0.95, P < 0.0001), GCF(C-11-GLU) (slope = 0.79, r = 0.97, P < 0.0001), and OF(C-11-GLU) (slope = 0.70, r = 0.96, P < 0.0001), respectively. M-GNF(GLU)/M-EF(GLU) strongly correlated with fractional C-13-content (r = 0.92, P < 0.0001). Conclusion: Under nonischemic conditions, it is feasible to measure myocardial glucose metabolism noninvasively beyond its initial extraction with PET using 1-C-11-glucose and a compartmental modeling approach that takes into account uptake and oxidation of secondarily labeled exogenous C-11-lactate.