Sage Journals: Discover world-class research

Abstract

Tumor-selective macromolecular ligands containing 5-(p-Carbonyloxyphenyl)-10,15,20-triphenylporphyrin (HPTP) moiety (PHEA-DTPAHPTP and PAEA-DTPA-HPTP) were prepared by the incorporation of diethylenetriaminepentaacetic acid (DTPA) and 5-(p-hydroxylphenyl)-10,15, 20-triphenylporphyrin (HPTP) as the tumor-selective group in poly [α,β-(N-(2-hydroxyethyl)-L-aspartamide)] (PHEA) and poly-[α-β-(N-(2-aminoethy1)-L-aspartamide)] (PAEA). These ligands were further complexed with gadolinium chloride to form two tumor-selective macromolecular MRI contrast agents PHEA-Gd-DTPA-HPTP and PAEA-Gd-DTPA-HPTP. Relaxivity studies showed that both the polyaspartamide-gadolinium complexes possess higher relaxation effectiveness than that of the clinically used Gd-DTPA. Magnetic resonance imaging of tumors in mice indicated that these two polyaspartamide MRI contrast agents containing 5-(p-Carbonlyoxyphenyl)-10,15,20-triphenylporphyrin moiety can significantly enhance the contrast MRIs of Hepatoma (H₂₂) and Ehrlich ascites carcinoma after injection and are taken up selectively by these cancers in mice.

Get full access to this article

View all access options for this article.

References

1. Caravan, P. , Ellison, J.J. , Mcmurry, T.J. and Lauffer, R.B. (1999). Gadolinium (III) chelates as MRI contrast agents: structure, dynamics, and applications. Chem. Rev., 99: 2293–2352.

2. Lauffer, R.B. (1987). Paramagnetic metal complexes as water proton relaxation agents for NMR imaging: theory and design. Chem. Rev., 87: 901–927.

3. Wen, J. , Zhuo, R.X. and Wang, L. (1998). Aromatic DTPA-bis(amide) gadolinium complexes as hepatobiliary contrast agents for magnetic resonance imaging. Chin. J. Magn. Reson., 15: 217–221.

4. Yan, G.P. and Zhuo, R.X. (2001). Research progress of magnetic resonance imaging contrast agents. Chinese Science Bulletin, 46: 531–538.

5. Waldmann, T.A. (1991). Monoclonal antibodies in diagnosis and therapy. Science, 252: 1657–1662.

6. Kearney, A.S. (1996). Prodrugs and targeted drug delivery. Advanced Drug Delivery Review 19: 225–239.

7. Wiener, E.C. , Konda, S. , Shadron, A. , Brechbiel, M. and Gansow, O. (1997). Targeting dendrimer-chelates to tumors and tumor cells expressing the high-affinity folate receptor. Invest. Radiol., 32: 748–754.

8. Young, S.W. , Wright, M. , Sessler, J.L. , Mody, T.D. and Magda, D. (1997). Texaphyrin-lipophilic molecule-vesicle complexes, membrane incorporation of texaphyrins, and use in diagnosis and therapy. PCT Int. Appl. WO 97 46, 262-262 (Dec.11.

9. Luo, Y. , Mei, E.W. and Zhuo, R.X. (1995). Studies on water-soluble metalloporphyrins as tumor targeting magnetic resonance imaging contrast agents. Chemical Journal of Chinese Universities, 16: 1629–1632.

10.

10. Shi, Z.J. , He, K.X. , Gao, X.H. and Zhang, X.L. (1993). Synthesis and pharmacologic effect of α, β-poly-DL-asparimide containing MTX and HPD, a potential polymer targeting antitumor drug. Chinese Journal of Pharmaceuticals, 24: 352–354.

11.

11. Giammona, G. , Carlisi, B. and Palazzo, S. (1987).α, β-Poly (N-hydroxyethyl) DL-aspartamide with derivatives of carboxylic acids. J. Polym. Sci. Polym. Chem., 25: 2813–2818.

12.

12. Giammona, G. , Carlisi, B. , Cavallaro, G. , Donato, I. , Pinio F. and Turco Liveri, V. (1990). Calorimetric investigation of the interaction between, poly(N-hydroxyethyl)-DL-aspartamide and surfactants. Int. J. Pharm., 64: 239–242.

13.

13. Giammona, G. , Carlisi, B. , Pitarresi, G. and Fontana, G. (1991). Hydrophilic and hydropholic polymeric derivatives of antiinflammatory agents such as Alclofenac, Ketoprofen and Ibuprofen. J. Bioact. Compatible polym., 6: 129–141.

14.

14. Giammona, G. , Carlisi, B. , Pitarresi, G. , Cavallaro, G. and Turco Liveri, V. (1992). Water-soluble copolymers of an antiviral agent: Synthesis and their interaction with a biomembrane model. J. Control. Release, 22: 197–204.

15.

15. Giammona, G. , Cavallaro, G. , Fontana, G. , Pitarresi, G. and Carlisi, B. (1998). Coupling of the antiviral agent zidovudine to polyaspartamide and in vitro drug release studies. J. Control. Release, 54: 321–331.

16.

16. Saudek, V. , Drobnik, J. , Havranova, M. and Cechova, D. (1982). High molecular weight derivative of Trypsin-Kallikrein inhibitor for potential medical use: preparation and characterization. Macromol. Chem., 183: 1473–1484.

17.

17. Yan, G.P. , Zhuo, R.X. , Xu, M.Y. , Li, L.Y. and Tang, Y.F. (2001). Livertargeting macromolecular MRI contrast agents. Science in China (Series B), 44: 344–352.

18.

18. Yan, G.P. , Zhuo, R.X. and Zheng, C.Y. (2001). Study on the anticancer drug 5-fluorouracil-conjugated polyaspartamides containing hepatocyte-targeting group. J. Bioact. Compatible polym., 16: 277–293.

19.

19. Shi, F.Q. (1990). YiXue DongWu ShiYan FangFa, Chapter 4: 226–232.

20.

20. Li, P.Y. , Gao, C.Q. , Cheng, G.E. and Huang, S.Q. (1993). A study of porphyrin compounds (xx)–studies on synthesis and photoelectrochemical properties of 5-(p-hexadecyloxyphenyl)-10,15,20-triphenylporphyrin and 5-(p-hexadecanoyloxyphenyl)-10,15,20-triphenylporphyrin. Chemical Journal of Chinese Universities, 14: 360–362.

21.

21. Huang, W.D. and Chen, C.Q. (1985). Sythesis of polypeptides, pp. 14–15.

22.

22. Neuse, E.W. , Perlwitz, A.G. and Schmitt, S. (1991). Water-soluble polyamides as potential drug carriers. Macromol., 192: 35–50.

23.

23. Zhuo, R.X. , Fu, Y.J. and Liao, J. (1997). Synthesis, relaxivity and biodistribution of novel magnetic resonance imaging contrast agents: polylysine (Gd-DTPA/DOTA) with pendent galactose moieties as hepatocyte-targeting groups. Chin. Chem. Lett., 8: 157–160.

Tumor-Selective Macromolecular MRI Contrast Agents

Abstract

Get full access to this article

References