Synthesis and characterization of poly(HPMA)‐APMA‐DTPA‐99mTc for imaging‐guided drug delivery in hepatocellular carcinoma

To develop a theranostic agent for diagnostic imaging and treatment of  hepatocellular carcinoma (HCC), poly(HPMA)-APMA-DTPA-99mTc (HPMA: N-(2-hydroxypropyl methacrylamide; APMA: N-(3-aminopropyl)methacrylamide; DTPA: diethylenetriaminepentaacetic acid) and DTPA-99mTc were synthesized and characterized, and their HCC targeting was tested by in vitro cellular uptake and in vivo tumor imaging in this study. Radioactivity of HCC cells incubated with poly(HPMA)-APMA-DTPA-99mTc was significant higher (16.40%) than that of the cells incubated with DTPA-99mTc (2.98%). Scintigraphic images of HCC in mice obtained at 8 h after injection of poly(HPMA)-APMA-DTPA-99mTc showed increased radioactivity compared with that in mice injected with DTPA-99mTc. The results of postmortem tissue radioactivity assay demonstrated higher radioactivity of HCC tumor tissues (2.69 ± 0.15% ID/g) from the tumor-bearing mice injected with poly(HPMA)-APMA-DTPA-99mTc compared with that of HCC tumor tissues in the tumor-bearing mice injected with DTPA-99mTc (0.83 ± 0.03 %ID/g), (P <0.001). These results first directly confirm the significant passive hepatocellular tumor targeting of HPMA copolymer. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013