Interventional radionuclide therapy of hepatocellular carcinoma: Assessment of intratumoral retention of HPMA copolymers
2013
To develop new radiopharmaceuticals for the interventional radionuclide therapy of recurrent hepatocellular carcinoma, poly(HPMA)-APMA-DTPA[HPMA=N-(2-hydroxypropyl) methacrylamide; APMA=N-(3-aminopropyl)methacrylamide; DTPA=diethylenetriaminepentaacetic acid] was synthesized by free radical precipitation polymerization in acetone/dimethylsulfoxide with N,N′-azobis(isobutyronitrile) as the initiator. The copolymers were characterized with nuclear magnetic resonance(NMR) spectroscopy and gel permeation chromatography(GPC, M n=2.2×104, M w/M n=1.38). Subsequently, poly(HPMA)-APMA-DTPA was conjugated with 99mTc radionuclide. Prolonged retention of poly(HPMA)-APMA-DTPA conjugate within the tumor tissues was demonstrated by single-photon emission computed tomography computed tomography(SPECT-CT) at 1, 2, 4 and 24 h following intra-tumoral injection of the conjugate to hepatocellular carcinoma xenografts in mice. DTPA-99mTc was also synthesized and characterized for comparison. The data suggest that the poly(HPMA)-APMA-DTPA conjugates might be useful for the interventional radionuclide therapy of recurrent hepatocellular carcinoma in humans.
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