BACKGROUND: Chemokine receptor 4(CXCR4) plays an important role in the potential growth of pancreatic tumor and its ability to develop metastasis. Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles offer strong contrast-enhancing effect for MR imaging of pancreatic tissue. PURPOSE: To establish a biomarker-targeted nanoparticulate contrast agent CXCR4-USPIO for pancreatic cancer cell MR imaging and to investigate the relationship between in vitro MR T2 enhancement ratio, ΔR2 values, and the cellular CXCR4 expression levels. MATERIAL AND METHODS: The CXCR4 monoclonal antibody and bovine serum albumin (BSA) were bioconjugated with USPIO using carbodiimide. The T2 and T2* values of CXCR4-USPIO, BSA-USPIO, and USPIO were evaluated at the same iron concentration levels. After incubating four pancreatic cancer cell lines (AsPC-1, BxPC-3, CFPAC-1, PANC-1) with CXCR4-USPIO and BSA-USPIO, respectively, changes of T2 values were measured with a clinical 1.5-T MRI scanner. Western blot and immunofluorescence tests were applied to semi-quantitatively analyze the expression levels of CXCR4 in the four cell lines. RESULTS: MR imaging revealed a linear correlation between ΔR2 and ΔR2* values of CXCR4-USPIO nanoparticles and the iron concentrations. The T2 enhancement ratio and ΔR2 values of AsPC-1, BxPC-3, CFPAC-1, PANC-1 cell lines in the CXCR4-USPIO group exhibited strong correlation with the CXCR4 peptide relative grey values measured by western blot (r = 0.976, P = 0.024; r = 0.959, P = 0.041, respectively) and the mean fluorescence signal intensity detected by laser scanning confocal microscopy (r = 0.996, P = 0.004; r = 0.962, P = 0.038, respectively). CONCLUSION: The targeted probe CXCR4-USPIO was created for MR molecular imaging of pancreatic cancer cell lines. The T2 enhancement ratio and ΔR2 values of CXCR4-USPIO nanoparticles could semi-quantitatively assess the cellular CXCR4 expression levels.
BACKGROUND: Chemokine receptor 4(CXCR4) plays an important role in the potential growth of pancreatic tumor and its ability to develop metastasis. Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles offer strong contrast-enhancing effect for MR imaging of pancreatic tissue. PURPOSE: To establish a biomarker-targeted nanoparticulate contrast agent CXCR4-USPIO for pancreatic cancer cell MR imaging and to investigate the relationship between in vitro MR T2 enhancement ratio, ΔR2 values, and the cellular CXCR4 expression levels. MATERIAL AND METHODS: The CXCR4 monoclonal antibody and bovineserum albumin (BSA) were bioconjugated with USPIO using carbodiimide. The T2 and T2* values of CXCR4-USPIO, BSA-USPIO, and USPIO were evaluated at the same iron concentration levels. After incubating four pancreatic cancer cell lines (AsPC-1, BxPC-3, CFPAC-1, PANC-1) with CXCR4-USPIO and BSA-USPIO, respectively, changes of T2 values were measured with a clinical 1.5-T MRI scanner. Western blot and immunofluorescence tests were applied to semi-quantitatively analyze the expression levels of CXCR4 in the four cell lines. RESULTS: MR imaging revealed a linear correlation between ΔR2 and ΔR2* values of CXCR4-USPIO nanoparticles and the iron concentrations. The T2 enhancement ratio and ΔR2 values of AsPC-1, BxPC-3, CFPAC-1, PANC-1 cell lines in the CXCR4-USPIO group exhibited strong correlation with the CXCR4 peptide relative grey values measured by western blot (r = 0.976, P = 0.024; r = 0.959, P = 0.041, respectively) and the mean fluorescence signal intensity detected by laser scanning confocal microscopy (r = 0.996, P = 0.004; r = 0.962, P = 0.038, respectively). CONCLUSION: The targeted probe CXCR4-USPIO was created for MR molecular imaging of pancreatic cancer cell lines. The T2 enhancement ratio and ΔR2 values of CXCR4-USPIO nanoparticles could semi-quantitatively assess the cellular CXCR4 expression levels.
Authors: Ole Tietz; Nazila Kamaly; Graham Smith; Elham Shamsaei; Kishore K Bhakoo; Nicholas J Long; Eric O Aboagye Journal: Am J Nucl Med Mol Imaging Date: 2013-07-10