背景:缺氧是实体瘤的有害因素,导致攻击性和治疗抵抗。OMX,血红素一氧化氮/氧结合(H-NOX)蛋白家族的可调氧载体,有可能减少肿瘤缺氧。[18F]氟异硝唑([18F]FMISO)正电子发射断层扫描(PET)是最广泛使用和研究的肿瘤缺氧的非侵入性成像方法。在这项研究中,我们使用[18F]FMISOPET/CT(计算机断层扫描)评估OMX对自发性犬肿瘤缺氧的影响。
结果:将13例患有各种肿瘤的犬患者(n=14)随机分为两组,治疗组交替接受肿瘤内(IT)OMX注射(OMXIT组)和静脉(IV)OMX注射(OMXIV组)。如果最大肿瘤-肌肉比(TMRmax)大于1.4,则肿瘤被认为是缺氧。此外,在[18F]FMISOPET图像中,缺氧体积(HV)定义为肿瘤肌肉比大于1.4的区域.在OMXIT组中的6/7肿瘤和OMXIV注射组中的5/7肿瘤中检测到缺氧。尽管OMXIT组和IV组之间的基线缺氧没有显着差异,两组对OMX的反应不同.在OMXIV组中,缺氧肿瘤(n=5)表现出肿瘤缺氧的显著减少,如治疗后[18F]FMISOPET成像中TMRmax和HV降低所示。相比之下,OMXIT组(n=6)的低氧肿瘤显示[18F]FMISO摄取显着增加,TMRmax和HV变化。
结论:[18F]FMISOPET/CT成像是一种有前途的非侵入性方法,用于监测肿瘤缺氧并评估缺氧调节疗法在犬患者中的疗效。OMX在减少肿瘤缺氧方面显示出有希望的结果,特别是当静脉给药时,从[18F]FMISOPET成像中TMRmax和HV的降低可以看出。
BACKGROUND: Hypoxia is a detrimental factor in solid tumors, leading to aggressiveness and therapy resistance. OMX, a tunable oxygen carrier from the heme nitric oxide/oxygen-binding (H-NOX) protein family, has the potential to reduce tumor hypoxia. [18F]Fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) is the most widely used and investigated method for non-invasive imaging of tumor hypoxia. In this study, we used [18F]FMISO PET/CT (computed tomography) to assess the effect of OMX on tumor hypoxia in spontaneous canine tumors.
RESULTS: Thirteen canine patients with various tumors (n = 14) were randomly divided into blocks of two, with the treatment groups alternating between receiving intratumoral (IT) OMX injection (OMX IT group) and intravenous (IV) OMX injection (OMX IV group). Tumors were regarded as hypoxic if maximum tumor-to-muscle ratio (TMRmax) was greater than 1.4. In addition, hypoxic volume (HV) was defined as the region with tumor-to-muscle ratio greater than 1.4 on [18F]FMISO PET images. Hypoxia was detected in 6/7 tumors in the OMX IT group and 5/7 tumors in the OMX IV injection group. Although there was no significant difference in baseline hypoxia between the OMX IT and IV groups, the two groups showed different responses to OMX. In the OMX IV group, hypoxic tumors (n = 5) exhibited significant reductions in tumor hypoxia, as indicated by decreased TMRmax and HV in [18F]FMISO PET imaging after treatment. In contrast, hypoxic tumors in the OMX IT group (n = 6) displayed a significant increase in [18F]FMISO uptake and variable changes in TMRmax and HV.
CONCLUSIONS: [18F]FMISO PET/CT imaging presents a promising non-invasive procedure for monitoring tumor hypoxia and assessing the efficacy of hypoxia-modulating therapies in canine patients. OMX has shown promising outcomes in reducing tumor hypoxia, especially when administered intravenously, as evident from reductions in both TMRmax and HV in [18F]FMISO PET imaging.