Correlation of volumetric perfusion CT parameters with hypoxia inducible factor-1 alpha expression in a rabbit VX2 tumor model.
BACKGROUND
Hypoxia inducible factor-1 alpha (HIF-1α) plays a critical role in tumoral angiogenesis and HIF-1α overexpression is associated with an increased risk of patient mortality in many cancers. A number of studies have introduced perfusion computed tomography (CT) as a monitoring modality for antiangiogenic therapy.


OBJECTIVE
To investigate significance of volumetric perfusion CT parameters in relationship to HIF-1α expression in VX2 tumor rabbit models.


METHODS
Twenty VX2 carcinoma tumors of bilateral back muscles of 10 rabbits were evaluated with serial volumetric perfusion CT in 7, 10, and 14 days after tumor implantation. CT perfusion data were analyzed to calculate blood flow (BF), blood volume (BV), and permeability surface area product (PS) of whole tumor and non-necrotic peripheral area (periphery). Immunohistochemical analysis of HIF-1α expression and microvessel density (MVD) was performed.


RESULTS
HIF-1α was expressed in 12 tumors; two, three, and seven tumors classified as scores 1, 2 and 3, respectively. Mean MVD was 24.85 ± 13.7. PS of both the whole tumor and periphery showed positive correlations with HIF-1α score (r = 0.41, P = 0.046; r = 0.43, P = 0.002, respectively). BV of periphery showed a negative correlation with HIF-1α (r = -0.48, P = 0.040). There was strong positive correlation between HIF-1α expression and MVD (r = 0.82, P < 0.001).


CONCLUSIONS
In VX2 tumors, volumetric perfusion CT parameters were of limited value for the prediction of HIF-1α activity although HIF-1α expression was found to be weakly positively correlated with PS and negatively correlated with BV.
Department of Radiology, Seoul National University College of Medicine, and Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea Department of Radiology, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul, Republic of Korea.
Jung Im
JI
Kim
Department of Radiology, Seoul National University College of Medicine, and Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea leehyunju00@gmail.com.
Hyun-Ju
HJ
Lee
Department of Radiology, Seoul National University College of Medicine, and Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea.
Jin Mo
JM
Goo
Department of Pathology, Seoul National University College of Medicine, and Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea.
Min A
MA
Kim
Department of Pathology, Seoul National University College of Medicine, and Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea.
Doo Hyun
DH
Chung
D000818:Animals; D054893:Cone-Beam Computed Tomography; D003287:Contrast Media; D004195:Disease Models, Animal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D007472:Iohexol / Q000031:analogs & derivatives; D055806:Microvessels; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D011817:Rabbits; D012983:Soft Tissue Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*
D003287:Contrast Media; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007472:Iohexol; C038192:iopromide
Hypoxia inducible factor-1 alpha (HIF-1α); angiogenesis; microvessel density; perfusion computed tomography (CT)