The Quarterly Journal of Nuclear Medicine and Molecular Imaging 2020 Apr 14

DOI: 10.23736/S1824-4785.20.03208-2

Copyright © 2020 EDIZIONI MINERVA MEDICA

lingua: Inglese

Characterization of heterogeneity of hypoxia with 18FMISO PET/CT, BOLD fMRI and immunohistochemistry in human breast tumor xenograft: initial study

Jingyi CHENG ^{1, 2, 3, 4, 5}, Jianping ZHANG ^{1, 2, 3, 4, 5}, Simin HE ^{1, 2, 3, 4, 5}, Ming QI ^{1, 2, 3, 4, 5}, Yongping ZHANG ^{1, 2, 3, 4, 5}, Xiaoli ZHU ^{2, 6}, Yingjian ZHANG ^{1, 2, 3, 4, 5}, Jun ZHANG ^{7, 8}, Daoying GENG ^{7, 8} ✉

¹ Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China; ² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; ³ Center for Biomedical Imaging, Fudan University, Shanghai, China; ⁴ Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China; ⁵ Key Laboratory of Nuclear Physics and Ion-beam Application (MOE), Fudan University, Shanghai, China; ⁶ Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China; ⁷ Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China; ⁸ Institute of Functional and Molecular Medical Imaging, Fudan University, Shanghai, China

BACKGROUND: To demonstrate that both 18F-fluoromisonidazole positron emission tomography computed tomography (18F-MISO PET/CT) and function magnetic resonance imaging blood oxygenation level dependent (fMRI BOLD) can map intratumoral sub-region of hypoxia consistently.
METHODS: The MCF-7 xenograft was established and hypoxia were divided into three subtypes by animal 18F-MISO PET/CT scan. Using tumor to background ratio (TBR) >1.40 and hypoxia sub-volume (HSV) / tumor volume (TV) ≧ 50% as threshold, hypoxia was divided into non-hypoxia (NH), diffused-hypoxia (DH) and localized-hypoxia (LH). For NH and DH, unselective ROIs were delineated to calculate ΔT2*. For LH tumor, MIM software was used to fuse the PET/CT and MRI images rigidly and the selective ROIs were delineated to calculate ΔT2*. The ΔT2* of three hypoxic subtypes were compared each other. Finally, hypoxia-inducible factor (HIF)- 1α was assayed.
RESULTS: 62 xenografts were divided into 23 NHs, 11 DHs and 28 LHs. The ΔT2* of NH xenografts (62.80%±21.60%) were significantly different to ΔT2* of DH (15.10%±5.30%) and ΔT2* of hypoxic sub-regions in LH xenografts (16.60%±10.10%) (P<0.001 both). In LH xenografts, ΔT2* of nonhypoxic and hypoxic sub-regions were 50.07%±16.60% and 16.60%±10.10% respectively, which represented a significant difference (t=13.00, P<0.001). There were significant correlations between TBRs and HIF-1α scores in NH group (r=0.52, P=0.024) and DH group (r= 0.47, P=0.045), but not in LH group (r= -0.22, P=0.262).
CONCLUSIONS: Combining with TBR and HSV, hypoxic sub-region could be described more particularly and demonstrated by animal 18F-MISO PET/CT, animal BOLD fMRI and immunohistochemically analysis consistently.

KEY WORDS: Tumor hypoxia; Heterogeneity; Fluoromisonidazole; Positron emission tomography computed tomography; Magnetic resonance imaging