High rigid Gd (DO3VA) shows remarkable relaxivity: A novel class of MMI agent engineered for MR analysi
Vol 5, Issue 1, 2022
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Abstract
A novel dinuclear gadolinium(III) complex of an amide linked bispolyazatricarboxylate macrocycle (DO3VA) having 2-bromoisovaleric acid pendant arm is reported. The molecular longitudinal relaxivity of the dinuclear complex [Gd2{acamidoet(DO3VA)2}(H2O)2] is 13.23mM–1s–1 which corresponds to a “per Gd” relaxivity of 6.62 mM–1 s–1 (20 MHz, 37 ± 0.1 °C, pH 7). The “per Gd” r1p value is higher than the relaxivity of the clinically approved CAs. The transverse relaxivity (r2p) of [Gd2{acamidoet(DO3VA)2}(H2O)2] is 14.34 mM–1 s–1. The r2p/r1p values of 1.08 indicate that the complex is T1-weighted CAs. The 2-bromoisovaleric acid seems to be an excellent pendant arm for holding Gd(III) metal ion at any pH. The remarkable stability of the complex at various pH and in presence of protein shows that the ligand can be used as functionality in making new CAs for MRI and the amide core is a versatile core molecule for the creation of polynuclear gadolinium(III) chelates and dendrimeric CAs.
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1. Wahsner J, Gale EM, Rodriguez-Rodriguez A, et al. Chemistry of MRI contrast agents: Current challenges and new frontiers. Chemical Reviews 2019; 119: 957–1057.
2. Merbach AS, Helm L, Tóth E. The chemistry of contrast agents in medical magnetic resonance imaging; merbach. New York: John Wiley & Sons, Ltd.; 2001.
3. Shalviri A, Foltz DW, Cai P, et al. Multifunctional terpolymeric MRI contrast agent with superior signal enhancement in blood and tumor. Journal of Controlled Release 2013; 167: 11–20.
4. Jendrasiak LG, Smith LR, Ribeiro AA. The interaction of MRI contrast agents with phospholipids. Physics in Medicine and Biology 2000; 45: 3109–3122.
5. Louie AY, Huber MM, Ahrens ET, et al. Invivo visualization of gene expression using magnetic resonance imaging. Nature Biotechnology 2000; 18: 321–325.
6. Richardson JC, Bowtell RW, Mader K, et al. Pharmaceutical applications of magnetic resonance imaging (MRI). Advanced Drug Delivery Reviews 2005; 57: 1191–1209.
7. Caravan P. Strategies for increasing the sensitivity of gadolinium based MRI contrast agents. Chemical Society Reviews 2006; 35: 512–523.
8. Bianchi A, Calabi L, Corana F, et al. Thermodynamic and structural properties of Gd(III) complexes with polyamino-polycarboxylic ligands: basic compounds for the development of MRI contrast agents. Coordination Chemistry Reviews 2000; 204: 309–393.
9. Lauffer RE. Paramagnetic metal complexes as water proton relaxation agents for NMR imaging: Theory and design. Chemical Reviews 1987; 87: 901–927.
10. Aime S, Botta M, Terreno E. Gd(III)-based contrast agents for mri. Advances in Inorganic Chemistry 2005; 57: 173–237.
11. Kubicek V, Toth E. Design and function of metal complexes as contrast agents in MRI. Advances in Inorganic Chemistry 2009; 61: 63–129.
12. Terreno E, Castelli DD, Viale A, et al. Challenges for molecular magnetic resonance imaging. Chemical Reviews 2010; 110: 3019–3042.
13. Weinmann HJ, Brasch RC, Press WR, et al. Characteristics of gadolinium-DTPA complex: A potential NMR contrast agent. American Journal of Roentgenology 1984; 142: 619–624.
14. Penfield JG, Reilly RF. What nephrologists need to know about gadolinium. Nature Reviews Nephrology 2007; 3: 654–668.
15. Gu S, Kim H-K, Lee HG, et al. Gd-complexes of 1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′ -1,4,7,10-tetraacetic acid (DOTA) conjugates of tranexamates as a new class of blood-pool magnetic resonance imaging contrast agents. Journal of Medicinal Chemistry 2011; 54: 143–152.
16. Villaraza AJL, Bumb A, Brechbiel MW. Macromolecules, dendrimers, and nanomaterials in magnetic resonance imaging: The interplay between size, function, and pharmacokinetics. Chemical Reviews 2010; 110: 2921–2959.
17. Powell DH, Dhubhghaill OMN, Pubanz D, et al. Structural and dynamic parameters obtained from 17O NMR, EPR, and NMRD studies of monomeric and dimeric Gd3+ complexes of interest in magnetic resonance imaging: An Integrated and theoretically self-consistent approach. Journal of the American Chemical Society 1996; 118: 9333–9346.
18. Toth E, Helm L, Merbach AE. In: Merbach AE, Toth E (editors). The chemistry of contrast agents in medical magnetic resonance imaging. Weinheim, Germany: Wiley-VCH; 2001. p 45–119.
19. Caravan P. Protein-targeted gadolinium-based magnetic resonance imaging (MRI) contrast agents: Design and mechanism of action. Accounts of Chemical Research 2009; 42: 851–862.
20. Plush ES, Woods M, Zhou FY, et al. Nanoassembled capsules as delivery vehicles for large payloads of high relaxivity Gd3+ agents. Journal of the American Chemical Society 2009; 131: 15918–15923.
21. Wiener CE, Abadjian M-C, Sengar R, et al. Bifunctional chelates optimized for molecular MRI. Inorganic Chemistry 2014; 53: 6554−6568.
22. Jebasingh B, Alexander V. Synthesis and relaxivity studies of a tetranuclear gadolinium(III) complex of DO3A as a contrast-enhancing agent for MRI inorg. Chemistry 2005; 44: 9434–9443.
23. Roglin L, Lempens EHM, Meijer EW. A synthetic “tour de force”: Well‐defined multivalent and multimodal dendritic structures for biomedical applications. Angewandte Chemie International Edition 2011; 50: 102–112.
24. Mintzer MA, Grinstaff MW. Biomedical applications of dendrimers: A tutorial. Chemical Society Reviews 2011; 40: 173–190.
25. Floyd WC, Klemm PJ, Smiles DE, et al. Conjugation effects of various linkers on Gd(III) MRI contrast agents with dendrimers: Optimizing the hydroxy pyridinonate (HOPO) ligands with nontoxic, degradable esteramide (EA) dendrimers for high relaxivity. Journal of the American Chemical Society 2011; 133: 2390–2393.
26. Dawson RMC, Elliott DC, Elliott WH, et al. Data for biochemical research. Oxford: Oxford University Press; 1969. p. 475–508.
27. Pearse AGE. In: Pearse AGE (editors). Histochemistry, theoretical and applied. Churchill Livingstone: Edinburgh; 1980. p. 167.
28. Gomori G. In: Kaplan NO, Colowick SP (editors). Methods in enzymology. New York: Academic Press Inc; 1955. p. 138.
29. Pushparaj LT, Alexander V. Synthesis and relaxivity measurements of novel Gd(III) complex of DOTVA as MRA contrast agents. International Journal of Applied Biomedical Engineering 2014; 8: 1–8.
30. Pushparaj LT, Alexander V. Development of novel dinuclear [Gd(III)DO3VA] complexes decorated with isovaleric acid as MRI contrast agents for tumor diagnosis. International Journal of Applied Biomedical Engineering 2016; 10: 11–17.
31. Pushparaj LT, Alexander V. Synthesis, pH and HSA binding study of novel dinuclear [Gd(III)DO3VA] complex as magnetic resonance imaging contrast agent. International Journal of Scientific Engineering and Research 2016; 7: 1600–1605.
32. Pushparaj LT, Alexander V. Trinuclear Gd(III) metal complex with amide core display remarkable enhancement in relaxivity. Applied Magnetic Resonance 2017; 48: 813–825.
33. Furniss BS, Hannaford AJ, Rogers V, et al. Vogel’s textbook of practical organic chemistry. 4th ed. English Language Book Society; 1976. p. 457–458.
34. Paris J, Gameiro C, Humblet V, et al. Auto-assembling of ditopic macrocyclic lanthanide chelates with transition-metal ions. Rigid multimetallic high relaxivity contrast agents for magnetic resonance imaging. Inorganic Chemistry 2006; 45: 5092–5102.
35. Meiboom S, Gill D. Modified spinecho method for measuring nuclear relaxation times. Review of Scientific Instruments 1958; 29: 688–691.
36. Kubieck K, Rudovsky J, Kotek J, et al. Bisphosphonate monoamide analogue of dota: A potential agent for bone targeting. Journal of the American Chemical Society 2005; 127: 16477–16485.
37. Nakamoto K. Infrared and raman spectra of inorganic and coordination compounds. 4th ed. New York: John Wiley & Sons, Inc; 1986.
38. Silverstein RM, Bassler GC, Morrill TC. Spectrometric Identification of organic compounds. 5th ed. New York: John Wiley & Sons, Inc; 1991.
39. Ranganathan RS, Fernandez ME, Kang SI, et al. New multimeric magnetic resonance imaging agents. Investigative Radiology 1998; 33: 779–797.
40. Henig J, Toth E, Engelmann J, et al. Macrocyclic Gd3+ chelates attached to a silsesquioxane core as potential magnetic resonance imaging contrast agents: Synthesis, physicochemical characterization, and stability studies. Inorganic Chemistry 2010; 49: 6124–6138.
DOI: https://doi.org/10.24294/ace.v5i1.447
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