Department of Radiotherapy and Radiooncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
J Nucl Med. 2010 Sep;51(9):1386-94. doi: 10.2967/jnumed.109.074336. Epub 2010 Aug 18.
Several kinetic models have been proposed to assess the underlying oxygenation status behind hypoxia tracer uptake and have shown advantages, compared with static analysis, in discriminating hypoxic regions. However, the quantitative assessment of mathematic models that take into consideration clinical applications and their biologic nature is still challenging. We performed a feasibility study to assess hypoxia kinetic models using voxelwise cross-analysis between the uptake of the perfusion tracer (15)O-H(2)O and the hypoxia tracer (18)F-fluoroazomycin arabinoside ((18)F-FAZA).
Five patients with advanced head and neck cancer were included. For each patient, dynamic sequences of (15)O-H(2)O for 5 min and (18)F-FAZA for 60 min were acquired consecutively after injections of approximately 1 GBq and 300 MBq of each tracer, respectively. The compartment model, Thorwarth model, Patlak plot, Logan plot, and Cho model were applied to model the process of tracer transport and accumulation under hypoxic conditions. The standard 1-tissue-compartment model was used to compute a perfusion map for each patient. The hypoxia kinetic models were based on the assumption of a positive correlation between tracer delivery and perfusion and a negative (inverse) correlation between tracer accumulation (hypoxia) and perfusion.
Positive correlations between tracer delivery and perfusion were observed for the Thorwarth and Cho models in all patients and for the reversible and irreversible 2-compartment models in 4 patients. Negative correlations between tracer accumulation and perfusion were observed for the reversible 2-compartment model in all patients and for the irreversible 2-compartment model and Cho model in 4 patients. When applied to normal skeletal muscle, the smallest correlation variance over all 5 patients was observed for the reversible 2-compartment model.
Hypoxia kinetic modeling delivers different information from static measurements. Different models generate different results for the same patient, and they even can lead to opposite physiologic interpretations. On the basis of our assessment of physiologic precision and robustness, the reversible 2-compartment model corresponds better to the expectations of our assumptions than the other investigated models.
评估使用灌注示踪剂（15）O-H2O 和缺氧示踪剂（18）F-氟代阿霉素阿拉伯糖苷（（18）F-FAZA）之间体素交叉分析评估缺氧动力学模型的可行性。
纳入 5 例晚期头颈部癌症患者。每位患者分别静脉注射约 1GBq 和 300MBq 的（15）O-H2O 和（18）F-FAZA 后，连续采集 5min 的（15）O-H2O 动态序列和 60min 的（18）F-FAZA 动态序列。分别应用房室模型、Thorwarth 模型、Patlak 图、Logan 图和 Cho 模型来模拟缺氧条件下示踪剂转运和积累的过程。标准的 1 组织室模型用于计算每位患者的灌注图。缺氧动力学模型基于示踪剂输送与灌注之间的正相关和示踪剂积累（缺氧）与灌注之间的负（逆）相关的假设。
在所有患者中，Thorwarth 和 Cho 模型均观察到示踪剂输送与灌注之间存在正相关，在 4 例患者中，可逆和不可逆的 2 室模型也观察到了这种相关性。在所有患者中，可逆 2 室模型观察到示踪剂积累与灌注之间存在负相关，在 4 例患者中，不可逆 2 室模型和 Cho 模型也观察到了这种相关性。当应用于正常骨骼肌时，5 例患者的相关性方差最小的是可逆 2 室模型。
缺氧动力学模型提供的信息与静态测量不同。对于同一患者，不同的模型会产生不同的结果，甚至可能导致相反的生理解释。基于我们对生理精度和稳健性的评估，与其他研究模型相比，可逆 2 室模型更符合我们假设的预期。
