Screening of radiotracer for diagnosis of colorectal cancer liver metastasis based on MACC1-SPON2

Metastasis-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.

Human 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.

The 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).

Early screening with ¹⁸F-FLT and ¹⁸F-FMISO tracers has important clinical value for the efficient diagnosis and treatment of colorectal cancer liver metastases.