1. Gadolinium(III) Introduction to a Lanthanide MRI Contrast Agent
Rinck P., Magnetic Resonance in Medicine

2. About Gd(III) Lanthanide, considered a “hard” acid
Typical coordination number:
Paramagnetic, 7 unpaired electrons
Roughly same size as Ca(II) ~ 0.99 Å → toxicity issue
The Actinide Research Quarterly
Elster, A. D., 2016
Gd0 electronic configuration

3. What Makes Gadolinium Different?
Extracellular intravenous agent, in use since 1988
Paramagnetism is the main reason for the role of Gd(III) in MRI
9 coordination allows chelation specificity
Tissue distinction, blood brain barrier permeability
Chemical Name
Product Name
[Gd(DTPA)(H2O)]2-
Magnevist
[Gd(DOTA)(H2O)]-
Dotarem
[Gd(DTPA-BMA)(H2O)]
Omniscan
[Gd(HP-DO3A)(H2O)]
ProHance
[Gd(DO3A-butrol)(H2O)]
Gadovist
Magnevist
Lauffer R. B, 1987
Dotarem
Sherry, A. D.; et al. 2009

4. Some Gd(III) Chelates
Cyclic
Linear

5. Gd(III) Complexes [Gd(BOPTA)(H2O)]2- (MultiHance)
[Gd(DOTA)(H2O)]- (Dotarem)
[Gd(DOTA)(H2O)]-
[Gd(DTPA)(H2O)]2-
LogK = 24.7
LogK = 22.5
LogKeff, pH 7.4 = 17.2
LogKeff, pH 7.4 = 18.4
[Gd(DTPA)(H2O)]2- (Magnevist)
Caravan, P.; et al. 1999
Sherry A. D.; et al. 2009

6. New Lanthanide Geometry
Senn, F.; et al., 2012
[Gd(DOTA)(H2O)]- (Dotarem)
Caravan, P.; et al. 1999

7. Importance of Water Exchange and Ligand
Interaction of protons from water is key to contrast agent
Inner sphere: many exchanges per second, bulk water interaction
Ligand has effect on this exchange
Outer sphere: H bonding from complex etc.
[Gd(DTPA)]2-
[Gd(DTPA)(H2O)]2-
Inner Sphere
[Gd(DTPA)(H2O)]2-
Outer Sphere
Elster, A. D., 2016

8. What Does an MRI Contrast Agent Do?
MRI is NMR, signal is the reradiation of energy after perturbation of nuclei
Greater proton (water) density, larger signal
Paramagnetism decreases relaxation time, increasing signal intensity
[Gd(DTPA)(H2O)]2- (Magnevist)
Gilbert, P., 2013

9. What Does an MRI Contrast Agent Do?
Gadolinium contrast agent decreases T1 relaxation time
T1 and T2 relaxation times change with a paramagnetic agent present
T1: decay to equilibrium parallel to magnetic field, Z component
T2: decay to X and Y equilibrium
T1-weighted
T2-weighted
Gd(III) Concentration:
1) None
2) Low
3) High
Elster, A. D.; et al. 1990

10. Toxicity
Similar size as calcium(II) can interrupt signalling if Gd(III) is not chelated
Transmetallation can occur with other endogenous metals, displacing Gd(III)
Fe(III), Cu(II), Zn(II)
Zn(II) in highest concentrations
Gadolinium can precipitate as a phosphate salt
Nephrogenic Systemic Fibrosis (NSF)
Prone to those with acute kidney injury/disease
Swelling, tightening, thickening, hardening of skin
Muscle weakness, bone pain
Mayo Clinic

11. Current and Future Work in Gd(III) MRI Agents
Understand toxicity mechanism
Optimize relaxivity
Ligand studies, molecular weight component
Improve Targeting
Antibody, protein coupling
Functional agents
Zhou, Z.; et al. 2013

12. Works Cited
The Actinide Research Quarterly: 1st Quarter
Caravan, P.; Ellison, J. J.; Mcmurry, T. J.; Lauffer, R. B. Chemical Reviews 1999, 99 (9), 2293–2352.
Direct Evidence of Gadolinium Deposition in Brain Tissues Following MRI Exams
Elster, A. D.; Sobol, W. T.; Hinson, W. H. Radiology 1990, 174 (2), 379–381.
Elster, A.D.; Gadolinium,
Gaillard, F.; Jones, J. MRI sequences (overview), Radiopaedia.org
Gilbert, P. ”Gadolinium Neutron Capture Therapy” 2013,
Johnson, K. A. MR Signal Sources
Lauffer, R. B. Chemical Reviews 1987, 87 (5), 901–927.
Moore, T. “T1 Decay” 2011,
Nephrogenic systemic fibrosis Mayo Foundation for Medical Education and Research,
Rinck P. Magnetic Resonance in Medicine. The Basic Textbook of the European Magnetic Resonance Forum Electronic version 10.
Senn, F.; Helm, L.; Borel, A.; Daul, C. A. Comptes Rendus Chimie 2012, 15 (2-3), 250–254.
Sherry, A. D.; Caravan, P.; Lenkinski, R. E. Journal of Magnetic Resonance Imaging 2009, 30 (6), 1240–1248.
Takahashi, M.; Tsutsui, H.; Murayama, C.; Miyazawa, T.; Fritz-Zieroth, B. Magnetic Resonance Imaging 1996, 14 (6), 619–623.
Zhou, Z.; Lu, Z.-R. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 2013, 5 (2), 190–190.