一种缺氧 PET 示踪剂 [¹⁸F]HX4、[¹⁸F]FAZA 和 [¹⁸F]FMISO 在临床前肿瘤模型中的比较研究。

A comparative study of the hypoxia PET tracers [¹⁸F]HX4, [¹⁸F]FAZA, and [¹⁸F]FMISO in a preclinical tumor model.

机构信息

Department of Radiation Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.

出版信息

Int J Radiat Oncol Biol Phys. 2015 Feb 1;91(2):351-9. doi: 10.1016/j.ijrobp.2014.09.045. Epub 2014 Dec 6.

DOI:10.1016/j.ijrobp.2014.09.045

PMID:25491505

Abstract

PURPOSE

Several individual clinical and preclinical studies have shown the possibility of evaluating tumor hypoxia by using noninvasive positron emission tomography (PET). The current study compared 3 hypoxia PET tracers frequently used in the clinic, [(18)F]FMISO, [(18)F]FAZA, and [(18)F]HX4, in a preclinical tumor model. Tracer uptake was evaluated for the optimal time point for imaging, tumor-to-blood ratios (TBR), spatial reproducibility, and sensitivity to oxygen modification.

METHODS AND MATERIALS

PET/computed tomography (CT) images of rhabdomyosarcoma R1-bearing WAG/Rij rats were acquired at multiple time points post injection (p.i.) with one of the hypoxia tracers. TBR values were calculated, and reproducibility was investigated by voxel-to-voxel analysis, represented as correlation coefficients (R) or Dice similarity coefficient of the high-uptake volume. Tumor oxygen modifications were induced by exposure to either carbogen/nicotinamide treatment or 7% oxygen breathing.

RESULTS

TBR was stabilized and maximal at 2 hours p.i. for [(18)F]FAZA (4.0 ± 0.5) and at 3 hours p.i. for [(18)F]HX4 (7.2 ± 0.7), whereas [(18)F]FMISO showed a constant increasing TBR (9.0 ± 0.8 at 6 hours p.i.). High spatial reproducibility was observed by voxel-to-voxel comparisons and Dice similarity coefficient calculations on the 30% highest uptake volume for both [(18)F]FMISO (R = 0.86; Dice coefficient = 0.76) and [(18)F]HX4 (R = 0.76; Dice coefficient = 0.70), whereas [(18)F]FAZA was less reproducible (R = 0.52; Dice coefficient = 0.49). Modifying the hypoxic fraction resulted in enhanced mean standardized uptake values for both [(18)F]HX4 and [(18)F]FAZA upon 7% oxygen breathing. Only [(18)F]FMISO uptake was found to be reversible upon exposure to nicotinamide and carbogen.

CONCLUSIONS

This study indicates that each tracer has its own strengths and, depending on the question to be answered, a different tracer can be put forward.

摘要

目的

多项临床前和临床研究表明，使用非侵入性正电子发射断层扫描（PET）评估肿瘤缺氧是可能的。本研究比较了三种在临床上常用的缺氧 PET 示踪剂，[18F]FMISO、[18F]FAZA 和[18F]HX4，在一个临床前肿瘤模型中。评估了最佳成像时间点、肿瘤与血液比值（TBR）、空间再现性和对氧修饰的敏感性。

方法和材料

在注射后多个时间点（p.i.），用其中一种缺氧示踪剂对横纹肌肉瘤 R1 荷瘤 WAG/Rij 大鼠进行正电子发射计算机断层扫描（PET/CT）成像。计算 TBR 值，并通过体素到体素分析研究再现性，用相关系数（R）或高摄取体积的 Dice 相似系数表示。通过暴露于卡泊芬净/烟酰胺治疗或 7%氧气呼吸来诱导肿瘤氧修饰。

结果

[18F]FAZA 的 TBR 在 2 小时 p.i.时稳定且最大（4.0 ± 0.5），[18F]HX4 在 3 小时 p.i.时最大（7.2 ± 0.7），而[18F]FMISO 的 TBR 则持续增加（6 小时 p.i.时为 9.0 ± 0.8）。通过体素到体素比较和 30%最高摄取体积的 Dice 相似系数计算，发现[18F]FMISO（R = 0.86；Dice 系数= 0.76）和[18F]HX4（R = 0.76；Dice 系数= 0.70）具有较高的空间再现性，而[18F]FAZA 的再现性较差（R = 0.52；Dice 系数= 0.49）。在 7%氧气呼吸时，缺氧分数的改变导致[18F]HX4 和[18F]FAZA 的平均标准化摄取值增加。只有[18F]FMISO 的摄取在暴露于烟酰胺和卡泊芬净时被发现是可逆的。