Abstract
MP-2269, the Gd(III) complex of 4-pcntylbicyclo[2.2.2] octane-l-carboxyl-di-L-aspartyl-lysinc-derived-DTPA, is a small Gd-agent that binds non-covalently to scrum albumin in vivo to assume the enhanced relaxivities associated with macromolecular agents, (due in part to increased rotational correlation time, τR). To further explore the fundamental parameters that govern the dynamics of water proton relaxation enhancement by this prototypical albumin-binding agent, the rotational correlation time (τR) for the deuterated La(III) analog of MP-2269 has been independently measured in the presence and absence of 4% albumin using2H-NMR approaches. The diamagnetic La(III) analog of MP-2269 was deuterated at the α-position of the carbonyl groups.2H-NMR studies were conducted at 7.05T (46 MHz) and 310°K on a Bruker NMR spectrometer. Spectral deconvolution permitted calculation of transverse relaxation rates, 1/T2, from the NMR linewidths and subsequently, τR. The results yielded a τR of the albumin bound complex of ∼ 8 ns. This value is intermediate between those earlier estimated by17O-NMR (∼ 1 ns) and1H-NMRD (∼ 20–50 ns) and significantly shorter than that of albumin. The2H-NMR study results also indicate that the exchange between free and albumin-bound forms of the La(III) analog is slow (exchange lifetimes > 1 ms). This slow exchange does not affect the water residence lifetimes (τM 140-280 ns).
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Toth E, Connac F, Helm L, Adzamli K, Merbach AE. Direct assessment of water exchange on a Gd(III) chelate bound to a protein. J Biol Inorg Chem 1998;3:606–13.
Adzamli K, Toth E, Periasamy MP, Koenig SH, Merbach AE, Adams MD.1H-NMRD and17O-NMR assessment of water exchange and rotational dynamics of two potential MRI agents: MP-1177 (an extracellular agent) and MP-2269 (a blood pool agent). MAGMA 1999;8:163–71.
Kellar KE, Henrichs PM, Spiller M, Koenig SH. Relaxation of solvent protons by solute Gd3+-chelates, revisited. Magn Reson Med 1997;37:730–5.
Powell DH, Dhubhghaill OM, Pubanz D, Helm L, Lebedev YS, Schlaepfer W, Merbach AE. Structural and dynamic parameters obtained from17O-NMR, EPR and NMRD studies of monomeric and dimeric Gd3+ complexes of interest in magnetic resonance imaging: an integrated and theoretically self-consistent approach. J Am Chem Soc 1996;118:9333–46.
Ogan MD, Schmiedl U, Moseley ME, Grodd W, Paajanen H, Brasch RC. Albumin labeled with Gd-DTPA: an intravascular contrast-enhancing agent for magnetic resonance blood pool imaging: preparation and characterization. Invest Radiol 1987;22:665–71.
Adam G, Neuerburg J, Spuntrup E, Muhler A, Scherer K. Gd-DTPA-cascade polymer: potential blood pool contrast agent for MRI. J Magn Reson Imaging 1994;4:462–6.
Lauffer RB. Brady TJ, Brown III RD, Baglin C, Koenig SH. 1 T1 NMRD profiles of solutions of Mn2+ and Gd3+ protein-chelate conjugates. Magn Reson Med 1986;3:541–8.
Wallace RA, Haar JP, Miller DB, et al. Synthesis and preliminary evaluation of a small-molecule blood pool MR contrast agent. Magn Reson Med 1998;39:733–9.
Lauffer RB, Parmelee DJ, Dunham SU, Ouellet HS, Dolan RP, Witte S, McMurry TJ, Walovitch RC. MS-325: albumin-targeted contrast agent for MR angiography. Radiology 1998;207:529–38.
Adzamli K, Spiller M, Koenig SH. Water-Proton Relaxation by a non-covalent albumin-binding Gadolinium-chelate: An NMRD study of a potential blood pool agent, Acad Radiol 2000. in press.
Muller RN, Radüchel B, Laurent S, Platzek J, Piérart C, Mareski P, Vander Elst L. Physicochemical characterization of MS-325, a new gadolinium complex, by multinuclear relaxometry, Eur J Inorg Chem 1999;1949-1955.
Vander Elst L, Maton F, Laurent S, Seghi F, Chapelle F, Muller RN. A multinuclear MR study of Gd-EOB-DTPA: comprehensive preclinical characterization of an organ specific MRI contrast agent. Magn Reson Med 1997;38:604–614.
Wheeler WD, Legg JI. Assignment of the deuteron NMR spectra of chromium (III) complexes with EDTA and related ligands. Inorg Chem 1985;24:1292–7.
Aime S, Chiaussa M, Digilio G. Gianolio E, Terreno E. Contrast agents for magnetic resonance angiographic applications:1H and17O-NMR relaxometric investigations on two gadolinium(III) DTPA-like chelates endowed with high binding affinity to human serum albumin. J Biol Inorg Chem 1999;4:766–74.
Caravan P. Buke JWM, Dunham SU, Amedio J, Lauffer RB. T1 and T2 NMRD studies of ANGIOMARK™ (MS-325). In: Proceedings of the International Society of Magnetic Resonance in Medicine. Seventh Annual Meeting, 1999, p.724.
Vander Elst et al. submitted to MAGMA.
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Adzamli, K., Vander Elst, L., Laurent, S. et al. Deuterium NMR study of the MP-2269: albumin interaction — a step forward to the dynamics of non-covalent binding. MAGMA 12, 92–95 (2001). https://doi.org/10.1007/BF02668088
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DOI: https://doi.org/10.1007/BF02668088