Using dual-tracer PET to predict the biologic behavior of human colorectal cancer.
(18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) have been proven useful in diagnosing and staging many types of cancer but with emphasis on different aspects of tumor biology. The aim of the current study was to evaluate whether (18)F-FDG and (18)F-FLT can be used complementarily in monitoring the biologic characteristics of colorectal cancer (CRC).


METHODS
Human CRC cell lines SW480 and SW620 of the same genetic origin but different metastatic potential were cultured and implanted into nude mice to create CRC models. Uptake of (18)F-FDG and (18)F-FLT in SW480 and SW620 cells in vitro was assessed after incubation with radiotracers for 0, 30, 60, 90, and 120 min. In vivo imaging of SW480 and SW620 tumor-bearing mice was performed using small-animal PET/CT at 60 min after injection of each tracer. A region of interest was drawn over tumor and background to calculate the tumor-to-nontumor ratio (T/NT) using software on reconstructed images. Tumor growth rate, metastatic status, and survival time were assessed in tumor-bearing mice. The relationship between uptake of the tracers, metastatic capability, and tumor marker expression was evaluated using linear regression.


RESULTS
SW480 tumors grew more quickly than SW620 tumors (t = 3.332, P = 0.004). A higher incidence of lung and liver metastases was noted for SW480 than for SW620 (P = 0.023). Uptake in SW480 and SW620 cells was significantly different between (18)F-FDG and (18)F-FLT (t = 2.507, P = 0.021, vs. t = 3.497, P = 0.002). In the small-animal PET study, the T/NT of (18)F-FDG did not differ between SW480 and SW620 tumors (2.69 +/- 0.98 vs. 3.09 +/- 1.26, P = 0.524), but the T/NT of (18)F-FLT differed significantly between SW480 and SW620 tumors (3.65 +/- 0.51 vs. 2.22 +/- 0.42, P < 0.001). Heat shock protein 27 (HSP27) expression and integrin beta(3) expression were higher, whereas vascular endothelial growth factor receptor 2 (VEGFR2) expression and Ki67 expression were lower, in SW480 cells than in SW620 cells. For SW480, metastases in lung and liver correlated significantly with (18)F-FLT uptake in tumors (r = 0.763, P = 0.005) and with expression of HSP27 (r = 0.894, P = 0.008) and integrin beta(3) (r = 0.635, P = 0.088). A correlation was also found between (18)F-FLT uptake and expression of HSP27 (r = 0.924, P = 0.004) and integrin beta(3) (r = 0.813, P = 0.025). No correlation was found between (18)F-FDG uptake in tumors and metastasis in lung and liver (r = -0.111, P = 0.388). However, there was a significantly negative correlation between (18)F-FDG uptake and the survival time of tumor-bearing mice (r = -0.500, P = 0.017), to which (18)F-FLT did not relate (r = 0.262, P = 0.182).


CONCLUSIONS
High uptake of (18)F-FDG and (18)F-FLT may reflect poorer survival and a higher metastatic potential for CRC in mice. Combining (18)F-FDG with (18)F-FLT PET would be helpful in better predicting the biologic behavior of CRC.
Wang
Hui
H
Nuclear Medicine Department, General Hospital of the Chinese People's Liberation Army and Military Medical Postgraduate College, Beijing, China.
Zhang
Jinming
J
Tian
Jiahe
J
Qu
Baolin
B
Li
Tianran
T
Chen
Yingmao
Y
Liu
Jian
J
Wang
Shan
S
D000818:Animals; D001692:Biological Transport; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D015224:Dideoxynucleosides / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016014:Linear Models; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography; D011849:Radioactive Tracers; D014057:Tomography, X-Ray Computed
D015224:Dideoxynucleosides; D011849:Radioactive Tracers; D019788:Fluorodeoxyglucose F18; C002854:alovudine