Multiparametric monitoring of early response to antiangiogenic therapy: a sequential perfusion CT and PET/CT study in a rabbit VX2 tumor model.
OBJECTIVE
To perform dual analysis of tumor perfusion and glucose metabolism using perfusion CT and FDG-PET/CT for the purpose of monitoring the early response to bevacizumab therapy in rabbit VX2 tumor models and to assess added value of FDG-PET to perfusion CT.


METHODS
Twenty-four VX2 carcinoma tumors implanted in bilateral back muscles of 12 rabbits were evaluated. Serial concurrent perfusion CT and FDG-PET/CT were performed before and 3, 7, and 14 days after bevacizumab therapy (treatment group) or saline infusion (control group). Perfusion CT was analyzed to calculate blood flow (BF), blood volume (BV), and permeability surface area product (PS); FDG-PET was analyzed to calculate SUVmax, SUVmean, total lesion glycolysis (TLG), entropy, and homogeneity. The flow-metabolic ratio (FMR) was also calculated and immunohistochemical analysis of microvessel density (MVD) was performed.


RESULTS
On day 14, BF and BV in the treatment group were significantly lower than in the control group. There were no significant differences in all FDG-PET-derived parameters between both groups. In the treatment group, FMR prominently decreased after therapy and was positively correlated with MVD.


CONCLUSIONS
In VX2 tumors, FMR could provide further insight into the early antiangiogenic effect reflecting a mismatch in intratumor blood flow and metabolism.
Department of Radiology and Institute of Radiation Medicine, Seoul National University College of Medicine & Clinical Research Institute, Seoul National University Hospital, 101 Daehangno, Jongno-gu, Seoul 110-744, Republic of Korea ; Department of Radiology, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, 892 Dongnam-ro, Gangdong-gu, Seoul 134- 727, Republic of Korea.
Jung Im
0000-0001-6242-486X
JI
Kim
Department of Radiology and Institute of Radiation Medicine, Seoul National University College of Medicine & Clinical Research Institute, Seoul National University Hospital, 101 Daehangno, Jongno-gu, Seoul 110-744, Republic of Korea.
Hyun-Ju
HJ
Lee
Biomedical Engineering Branch, Division of Convergence Technology, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-769, Republic of Korea.
Young Jae
0000-0003-0443-0051
YJ
Kim
Biomedical Engineering Branch, Division of Convergence Technology, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-769, Republic of Korea.
Kwang Gi
0000-0001-9714-6038
KG
Kim
Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, 173 Beon-Gil, Bundang-Gu, Gyeonggi-do 463-707, Republic of Korea.
Kyung Won
KW
Lee
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, 173 Beon-Gil, Bundang-Gu, Gyeonggi-do 463-707, Republic of Korea.
Jae Ho
0000-0002-4766-1231
JH
Lee
Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, 173 Beon-Gil, Bundang-Gu, Gyeonggi-do 463-707, Republic of Korea.
Hak Jong
HJ
Lee
Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, 173 Beon-Gil, Bundang-Gu, Gyeonggi-do 463-707, Republic of Korea.
Won Woo
WW
Lee
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000068258:Bevacizumab; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D006801:Humans; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D010477:Perfusion; D049268:Positron-Emission Tomography; D011817:Rabbits; D014057:Tomography, X-Ray Computed
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D005947:Glucose