Abstract: Background and purpose: Transferrin (Tf) receptor (TfR) is expressed broadly in malignant cells, and has been developed as a target for anti-tumor therapy. This study aimed to investigate the feasibility of ^99mTc-Tf-DTPA-Gd noninvasively detecting tumor TfR expression in vivo. Methods: We established 10 xenograft tumor models with mice. ^99mTc-Tf-DTPA-Gd and Tf-DTPA-Gd were injected into mice via tail vein respectively, and 4 hours later single-photon emission computed tomography (SPECT)/ computed tomography (CT) and magnetic resonance imaging (MRI) were acquired. The values of target-to-muscle ratios (T/M) and relative signal enhancement (rSE) were calculated by drawing regions of interest (ROI) in tumors. H-E staining and immunohistochemistry detection were applied when imaging was completed. Statistical analysis was performed using two-sample t test. Results: The tumors were clearly visible except PC-3 after administration with ^99mTc-Tf-DTPA-Gd. The value of T/M between MDA-MB-468 and PC-3 showed statistically significant difference (t=6.919, P=0.002). In MRI experiment, the tumor of MDAMB-468 was enhanced distinctly, while the signal of PC-3 tumor approximated the pre-injection. The rSE between MDA-MB-468 and PC-3 also showed statistically significant difference (t=8.441, P=0.001). Immunohistochemistry staining showed 9 of these xenograft tumor models expressing TfR in various degree rather than PC-3 tumor. Conclusion: ^99mTc-Tf-DTPA-Gd could serve as an ideal probe for detecting tumor TfR expression in vivo noninvasively.

Key words: Transferrin receptor, Molecular imaging, Dual-modality, Magnetic resonance imaging, Immunohistochemistry