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Article Open Access

Tumor visualization and evaluation of glioblastoma in mice using small animal 9.4T MRI and PET‑CT with high resolution

  • Authors:
    • Shuangyi Li
    • Wenjiao Gu
    • Ying Jiang
    • Ting Liu
    • Limei Shuai
    • Yujie Wei
    • Youming Shi
    • Havyarimana Juvenal
    • Zhimin Wang
    • Yucai Wei
    • Bofan Wu
    • Xiaochun Zhou
    • Yumin Li
    • Futian Tang
  • View Affiliations / Copyright

    Affiliations: Department of Cardiovascular Disease, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu 730030, P.R. China, Gansu Province Key Laboratory of Environmental Oncology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu 730030, P.R. China, Department of PET/CT Center, Gansu Provincial People's Hospital, Lanzhou, Gansu 730030, P.R. China, Wuhan United Imaging Life Science Instrument Co., Ltd., Wuhan, Hubei 430206, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 71
    |
    Published online on: February 12, 2026
       https://doi.org/10.3892/or.2026.9076
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Abstract

Glioblastoma (GBM) is the most prevalent type of malignant primary brain tumor. Preclinical research serves a key role in investigating the development and mechanism of GBM tumor. However, the dynamic and non‑invasive evaluation of tumors in animals faces challenges, such as the limited sensitivity of clinical instruments and insufficient spatial resolution for mouse brain tumors. The present study aimed to establish an in vivo mouse GBM model and evaluate the model using high resolution small animal positron emission tomography‑computed tomography (PET‑CT) and magnetic resonance imaging (MRI). Metabolism was compared between the normal brain and tumor tissue by using 1H‑magnetic resonance spectroscopy (1H‑MRS). T2‑weighted imaging (T2WI) MRI detected the tumor in the brain 7 days after injection of GL261 cells, with tumor sizes of 1.263, 4.917 and 13.85 mm3 on days 7, 14 and 21, respectively. 1H‑MRS demonstrated that the levels of tissue metabolites such as lactate and total choline increased, while those representing neurological function of the brain such as total N‑acetylaspartate decreased in tumor compared with the normal brain tissues. PET‑CT imaging confirmed the tumor detected by MRI. At 6‑120 min post 18F‑fluorodeoxyglucose (FDG) administration, the standard uptake value (SUV) in tumor tissue gradually increased, while the SUV value in normal brain tissue gradually decreased. SUV in the liver and kidneys decreased, while SUV in the bladder increased in a time‑dependent manner. Pharmacokinetic analysis showed that the distribution of FDG in brain and tumor tissue conformed to a two‑tissue compartment model. This model consists of a plasma compartment and two tissue compartments representing free FDG and phosphorylated FDG within brain or tumor tissue. The model parameters are defined as follows: Fractional blood volume (vB)=3.6%, k1 (forward transport rate)=1.844, k2 (reverse transport rate)=3.844 and k3 (phosphorylation rate)=0.280 in brain and vB=2.3%, k1=0.797, k2=2.722 and k3=0.319 in tumor tissue, respectively. The tumors observed by MRI and PET‑CT imaging were ultimately confirmed through morphological and pathological analysis. Compared with normal brain tissue, glioma tissue exhibited significantly elevated glucose transporter type 1 protein levels. In conclusion, the model was confirmed by high‑resolution small animal PET‑CT and MRI, as well as morphological and pathological approaches.
View Figures

Figure 1

Experimental design. A total of 6
mice were orthotopically implanted with GL261 cells. A total of 7
days later, the tumor volume was determined using T2WI (red, tumor
ROI; yellow, normal tissue ROI). Spectra were acquired with a short
echo time point-resolved spectroscopy sequence. Small animal PET-CT
was used to evaluate the model by injecting FDG via tail vein and
analyze the pharmacokinetics of FDG. Western blot assay was
performed for molecular-level analysis of GLUT1 protein expression.
Morphological and pathological analyses were used to confirm the
final result. FDG, 18F-fluorodeoxyglucose; T2WI,
T2-weighted imaging; ROI, region of interest; GLUT1, glucose
transporter type1; 1H-MRS, 1H-magnetic
resonance spectroscopy.

Figure 2

Model of FDG metabolism in
glioblastoma mice. Two-compartments (plasma and brain tissue) and
the corresponding forward transfer coefficients (k1, k2, k3, and
k4) are used in the metabolism model of FDG. It is assumed that the
phosphorylation of FDG (k3) is a one-way process without
dephosphorylation (k4) and the forward transfer coefficient from
the precursor pool in brain tissue back into the plasma is
negligible as phosphorylated glucose and FDG are unable to cross
the blood-brain barrier. Figure adapted from (31). k1, the transport rate of FDG from
plasma into tissue; k2, the transport rate of free FDG from tissue
back to plasma; FDG-6-P, fluorodeoxyglucose-6-phosphate.

Figure 3

Dynamic and non-invasive evaluation
of GBM growth by MRI. Representative T2-weighted images of brain
for (A) normal C57 mice and gliomas from model mice at (B) 7, (C)
14 and (D) 21 days following cell injection (arrows indicate tumor
regions). (E) At day 21, mice had a significantly increased tumor
volume compared with days 7 and 14. n=6; *P<0.05. GBM,
glioblastoma.

Figure 4

Mean metabolite concentration and
ratios with tCr in normal and GBM mice. The peak area measurements
of the metabolites were used to calculate the metabolite
concentrations and ratios relative to (A): tCho, (B) tCr and (C)
tNAA concentration and (D) tNAA/tCr, (E) tCho/tCr, (F) tNAA/tCho
(F); Lip1.3/tCr ratio (G); Lac/tCr ratio (H); mI/tCr ratio (I).
n=6. *P<0.05. Group 1, normal mouse; group 2, normal
contralateral brain tissue of GBM mouse; group 3, tumor tissue of
GBM mouse. tCr, total creatine; GBM, glioblastoma; tCho, total
choline; tNAA, total N-acetylaspartate; Lip1.3, lipids at 1.3 ppm;
Lac, lactate; mI, myo-inositol.

Figure 5

Characteristics of FDG imaging in
tumor and normal mouse. (A) Normal and (B) tumor mice. Arrow, tumor
regions. FDG was specifically and selectively distributed in tumor
tissue rather than in normal brain tissue after extending the scan
time to 2 h. There was a time-dependent increase in the T/B ratio
(C). Comparison of T/B ratios at 1 and 2 h after FDG injection
revealed that the 2 h T/B ratio was significantly higher than the 1
h T/B ratio (D). FDG was rapidly distributed throughout the body of
the mice (E), but in the brain on the tumor side, FDG was absent
for the first 6 min, after which the FDG content in the tumor
tissue increased (F). SUV values in the normal mice kidneys (G),
tumor mice kidneys (H), normal mice livers (I) and tumor mice
livers (J) gradually decreased over time. Conversely, SUV values in
the normal mice bladders (K) and tumor mice bladders (L) exhibited
a time dependent upward trend. n=3. *P<0.05. T/B, tumor
tissue/background; FDG, 18F-fluorodeoxyglucose; SUV,
standardized uptake value; ID, injected dose.

Figure 6

Protein expression of GLUT1. (A)
Western blotting was performed to determine (B) expression of GLUT1
protein. n=3. *P<0.05. GLUT1, glucose transporter type1.

Figure 7

Gross and microscopic pathology of
glioma and brain tissue. Brain tissue of (A) normal mice was
structurally intact, while that of (B) tumor-bearing mice was
incomplete, and the tumor tissue was accompanied by necrotic
hemorrhage. Hematoxylin-eosin staining of (C) brain, (D) peritumor
and (E) tumor tissue showed heterogeneity of tumor cells (tumor
cells varied in size, distinct nucleoli, abundant and eosinophilic
cytoplasm, mitotic figures), accompanied by focal necrosis.
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Copy and paste a formatted citation
Spandidos Publications style
Li S, Gu W, Jiang Y, Liu T, Shuai L, Wei Y, Shi Y, Juvenal H, Wang Z, Wei Y, Wei Y, et al: Tumor visualization and evaluation of glioblastoma in mice using small animal 9.4T MRI and PET‑CT with high resolution. Oncol Rep 55: 71, 2026.
APA
Li, S., Gu, W., Jiang, Y., Liu, T., Shuai, L., Wei, Y. ... Tang, F. (2026). Tumor visualization and evaluation of glioblastoma in mice using small animal 9.4T MRI and PET‑CT with high resolution. Oncology Reports, 55, 71. https://doi.org/10.3892/or.2026.9076
MLA
Li, S., Gu, W., Jiang, Y., Liu, T., Shuai, L., Wei, Y., Shi, Y., Juvenal, H., Wang, Z., Wei, Y., Wu, B., Zhou, X., Li, Y., Tang, F."Tumor visualization and evaluation of glioblastoma in mice using small animal 9.4T MRI and PET‑CT with high resolution". Oncology Reports 55.4 (2026): 71.
Chicago
Li, S., Gu, W., Jiang, Y., Liu, T., Shuai, L., Wei, Y., Shi, Y., Juvenal, H., Wang, Z., Wei, Y., Wu, B., Zhou, X., Li, Y., Tang, F."Tumor visualization and evaluation of glioblastoma in mice using small animal 9.4T MRI and PET‑CT with high resolution". Oncology Reports 55, no. 4 (2026): 71. https://doi.org/10.3892/or.2026.9076
Copy and paste a formatted citation
x
Spandidos Publications style
Li S, Gu W, Jiang Y, Liu T, Shuai L, Wei Y, Shi Y, Juvenal H, Wang Z, Wei Y, Wei Y, et al: Tumor visualization and evaluation of glioblastoma in mice using small animal 9.4T MRI and PET‑CT with high resolution. Oncol Rep 55: 71, 2026.
APA
Li, S., Gu, W., Jiang, Y., Liu, T., Shuai, L., Wei, Y. ... Tang, F. (2026). Tumor visualization and evaluation of glioblastoma in mice using small animal 9.4T MRI and PET‑CT with high resolution. Oncology Reports, 55, 71. https://doi.org/10.3892/or.2026.9076
MLA
Li, S., Gu, W., Jiang, Y., Liu, T., Shuai, L., Wei, Y., Shi, Y., Juvenal, H., Wang, Z., Wei, Y., Wu, B., Zhou, X., Li, Y., Tang, F."Tumor visualization and evaluation of glioblastoma in mice using small animal 9.4T MRI and PET‑CT with high resolution". Oncology Reports 55.4 (2026): 71.
Chicago
Li, S., Gu, W., Jiang, Y., Liu, T., Shuai, L., Wei, Y., Shi, Y., Juvenal, H., Wang, Z., Wei, Y., Wu, B., Zhou, X., Li, Y., Tang, F."Tumor visualization and evaluation of glioblastoma in mice using small animal 9.4T MRI and PET‑CT with high resolution". Oncology Reports 55, no. 4 (2026): 71. https://doi.org/10.3892/or.2026.9076
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