Porphyrins typically show preferential uptake and retention by tumor tissues via receptor-mediated endocytosis of low-density lipoproteins. To investigate the relative importance of active and passive targeting strategies, the synthesis, characterization, in vitro uptake, and in vivo biodistribution of specific targeting porphyrin HPMA [HPMA: N-(2-hydroxypropyl)methacrylamide] copolymer tracer poly(HPMA)-porphyrin-DTPA-(99m)Tc (DTPA: diethylenetriaminepentaacetic acid), nonspecific targeting HPMA copolymer tracer poly(HPMA)-DTPA-(99m)Tc, and nontargeting tracer DTPA-(99m)Tc are described in this study. The results showed that the cellular accumulation of poly(HPMA)-porphyrin-DTPA-(99m)Tc complex was found to be time-dependent. The uptake of poly(HPMA)-porphyrin-DTPA-(99m)Tc was significantly higher than that of poly(HPMA)-DTPA-(99m)Tc, indicating that uptake of the poly(HPMA)-porphyrin-DTPA-(99m)Tc was active binding. The uptake of poly(HPMA)-DTPA-(99m)Tc was significantly higher than that of DTPA-(99m)Tc, suggesting that uptake of the poly(HPMA)-DTPA-(99m)Tc was passive binding. Twenty-four hour necropsy data in the hepatocellular carcinoma tumor model showed significantly higher (p < 0.001) tumor localization for poly(HPMA)-porphyrin-DTPA-(99m)Tc (5.18 ± 0.50% ID/g [percentage injected dose per gram tissue]) compared with poly(HPMA)-DTPA-(99m)Tc (2.69 ± 0.15% ID/g) and DTPA-(99m)Tc (0.83 ± 0.03% ID/g). Moreover, higher T/B for poly(HPMA)-porphyrin-DTPA-(99m)Tc indicated reduced extravasation of the targeted polymeric conjugates in normal tissues. Thus, the poly(HPMA)-porphyrin-DTPA-(99m)Tc is a potential macromolecular tumor targeting molecular agent.
Keywords: HPMA copolymers; biodistribution; macromolecular targeting carrier; porphyrin; specific targeting ligand.