Abstract
BackgroundMetastasis-associated in colon cancer 1 (MACC1) and Spondin2 (SPON2) are newly discovered oncogenes, but little is known about their role in colorectal cancer(CRC) liver metastases. PET has become an important molecular imaging technology due to its high sensitivity and quantifiability. In particular, its targeted, specific molecular probes can detect biological behaviors. This study was designed to evaluate the different biological properties of 18F-FDG, 18F-FLT, and 18F-FMISO PET. The value of the CRC liver metastasis model explores the correlation and potential mechanisms of three tracers uptakes with tumor-related biological characteristics.MethodsHuman CRC cell lines(LoVo and HCT8), were cultured for in vitro radionuclide uptake experiments to compare the molecular imaging features of colorectal cancer cells with different metastatic potentials. Two kinds of cells were injected into the spleen of nude mice to establish a liver metastasis model. After the tumor formation, three kinds of tracer PET images were performed to evaluate the characteristics of live PET imaging of high and low liver metastasis colorectal cancer models. The expression levels of MACC1 and SPON2 in tissues were detected by immunohistochemistry and Western blot. Correlation between tracer uptake and expression of MACC1 and SPON2 in liver metastases was assessed by linear regression analysis.ResultsThe uptake rate of in vitro three tracers uptake experiments was LoVo > HCT8. Micro-PET scan showed no significant difference between the 18F-FDG SUV values of the two cells (P > 0.05); there was significant difference between the 18F-FLT and 18F-FMISO SUV values (P < 0.05). All in vivo FLT and FMISO SUV values were significantly higher in LoVo tumors than in HCT8 tumors. The results of Western blot and immunohistochemistry showed that the expression levels of MACC1 and SPON2 in LoVo liver metastasis were higher than those in HCT8 (P < 0.05). The 18F-FLT SUVmax ratio was significantly correlated with the expression of MACC1 and SPON2 in hepatic metastases (r = 0.737, P = 0.0026; r = 0.842, P = 0.0002). The 18F-FMISO SUVmax ratio was only significantly correlated with the expression of MACC1 in hepatic metastasis (r = 0.770, P = 0.0013).ConclusionsEarly screening with 18F-FLT and 18F-FMISO tracers has important clinical value for the efficient diagnosis and treatment of colorectal cancer liver metastases.
Highlights
According to global cancer statistics in 2018, colorectal cancer (CRC) has become the fourth leading cause of death from cancer in the world, accounting for 10% of Extended author information available on the last page of the article the total number of cancers diagnosed and cancer-related deaths each year, and is the second most common cancer among women and men It is the third most common cancer, causing nearly 900,000 deaths each year
Our group established a correlation between GLUT-1 and HIF-1α by establishing molecular imaging features of liver metastasis nodules (18F-FMISO and 18F-FDG), in order to achieve early diagnosis of colorectal cancer liver metastasis [19]
Based on this study, the new tumor metastasis markers Metastasis-associated in colon cancer 1 (MACC1) and SPON2 were combined to detect the physiological function of liver metastasis of colorectal cancer
Summary
According to global cancer statistics in 2018, colorectal cancer (CRC) has become the fourth leading cause of death from cancer in the world, accounting for 10% of Extended author information available on the last page of the article the total number of cancers diagnosed and cancer-related deaths each year, and is the second most common cancer among women and men It is the third most common cancer, causing nearly 900,000 deaths each year. PET can display biological features within tumors in vivo at functional and molecular levels by means of targeted probes We can use this characteristic of PET to evaluate the biological characteristics (invasion and metastasis) of tumors, and to identify the high invasion and metastasis characteristics of colorectal cancer in advance, which is helpful for the appropriate treatment of liver metastasis of colorectal cancer. The value of the CRC liver metastasis model explores the correlation and potential mechanisms of three tracers uptakes with tumor-related biological characteristics. The results of Western blot and immunohistochemistry showed that the expression levels of MACC1 and SPON2 in LoVo liver metastasis were higher than those in HCT8 (P < 0.05). Conclusions Early screening with 18F-FLT and 18F-FMISO tracers has important clinical value for the efficient diagnosis and treatment of colorectal cancer liver metastases
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