title: Tumor targeting HPMA-porphyrin-99mTc copolymer molecular imaging agent.
abstract: 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.
authors.affiliation: a Department of Medicinal Chemistry , School of Pharmacy, Shandong University , Jinan 250012 , Shandong , China.
authors.forename: Long
authors.initials: L
authors.lastname: Yuan
authors.forename: Yabing
authors.initials: Y
authors.lastname: Ma
authors.forename: Jianchao
authors.initials: J
authors.lastname: Yuan
mesh_terms: D000178:Acrylamides / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000473:pathology; D045744:Cell Line, Tumor; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D004369:Pentetic Acid / Q000737:chemistry; D011166:Porphyrins / Q000737:chemistry*; D013667:Technetium
chemical_list: D000178:Acrylamides; D011166:Porphyrins; D013667:Technetium; D004369:Pentetic Acid; C032976:N-(2-hydroxypropyl)methacrylamide
keywords: HPMA copolymers; biodistribution; macromolecular targeting carrier; porphyrin; specific targeting ligand