Relaxivity R1 Research Articles

Colloidally Stable Monodisperse Fe Nanoparticles as T2 Contrast Agents for High-Field Clinical and Preclinical Magnetic Resonance Imaging

Iron nanoparticles (Fe NPs) produce negative contrast in magnetic resonance imaging (MRI) by shortening the transverse relaxation time (T2) of water protons at tissue sites. The high sensitivity of Fe toward oxidation under ambient conditions has challenged and impeded the development of stable Fe NPs for bioapplications compared to iron oxide nanoparticles (IONPs). This article demonstrates the synthesis of three batches of fairly monodisperse (size dispersion, <10%), colloidal Fe NPs with inorganic core diameters of 15.2, 12.0, and 8.8 nm. The 15.2 nm Fe NPs show high stability against oxidation, beyond 5 months, when dispersed in chloroform and deionized water. Upon dispersion in deionized water, these NPs gradually develop an amorphous iron oxide shell. On the contrary, upon transfer into water, the smaller Fe NPs oxidize to amorphous iron oxide eventually. The 15.2 nm Fe NPs exhibit much stronger shortening of the T2 relaxation time compared to the 12.0 and 8.8 nm Fe NPs at both high-field clinical 3 T and preclinical 9.4 T. The transverse relaxivity (r2) values of the 15.2 nm Fe NPs, based on per Fe ion concentration, were determined to be 167.9 mM–1 s–1 at 3 T and 236.4 mM–1 s–1 (higher than similarly sized IONPs) at 9.4 T. The respective r2/r1 ratios of 280 and 788 are high for a T2 contrast agent, although comprehensive MRI data for Fe NPs are not available in the literature for direct comparison. Fe NPs are promising MRI contrast agents for medical imaging.

Enhancing magnetic resonance imaging of bio-based nano-contrast via anchoring manganese on rod-shaped cellulose nanocrystals

Manganese-based nano materials used to enhance nano-contrasts in magnetic resonance imaging have low toxicity but suffer from a weak contrast imaging effect due to their low longitudinal relaxivity (r1). Moreover, the nanoparticle contrasts of manganese salt probably release manganese ions into the patient body during and after imaging process, causing potential toxicity problems. Thus, we took advantage of rod-shaped cellulose nanocrystals (CNCs) functionalized by diethylenetriamine pentaacetic dianhydride (coded as DCNCs) to anchor Mn2+ and improve its r1 for biocompatibility, highly chemical activity, and high specific area. Theoretical analysis indicated that the r1 could increase with the anchoring rate of Mn2+ on rod-shaped particles, and the large number of hydroxyl groups on CNCs made them able to carry as much as 5.9 mmol·g−1 of Mn2+. Then, we found the r1 increased linearly as the anchoring degree increased, up to 57.71 mM−1·s−1. The obtained DCNCs anchoring Mn2+ (Mn2+@DCNCs) nano-contrast showed low toxicity on RAW 264.7 and HUVEC, where the viability of the two cells was higher than 80%. Therefore, such a high r1 Mn2+-based material presents great advantage of commercial manganese and gadolinium contrasts, making the Mn2+@DCNCs of potential on diagnosing tumors and drug release.

Enhancing Tumor Accumulation and Cellular Uptake of Layered Double Hydroxide Nanoparticles by Coating/Detaching pH-Triggered Charge-Convertible Polymers.

Layered double hydroxide (LDH) nanoparticles are extensively explored as multifunctional nanocarriers due to their versatility in both the host layer and the interlayer anion. In this study, we report modification of positively charged Cu-containing LDH nanoparticles with a pH-responsive charge-changeable polymer to improve the particle colloidal stability in blood circulation, reduce the nonspecific uptake by normal cells in organs, and subsequently facilitate tumor accumulation and uptake by tumor cells in the acidic tumor microenvironment. In vitro experimental results demonstrate that this promising charge-convertible polymer–LDH nanocarrier well reduces the capture by macrophages in the physiologic medium (pH 7.4) but facilitates the uptake by tumor cells due to detaching of the coated polymer layer in the weakly acidic condition (pH 6.8). Cu-containing LDH nanoparticles also show pH-responsive magnetic resonance imaging (MRI) contrast capacity (i.e., r1 relaxivity). In vivo MRI further confirms effective tumor accumulation of the charge-convertible nanohybrids, with ∼4.8% of the injected dose accumulated at 24 h postintravenous injection, proving the potential as a versatile delivery nanocarrier to enhance the antitumor treatment.

Highly Potent MRI Contrast Agent Displaying Outstanding Sensitivity to Zinc Ions

AbstractZinc ions play an important role in numerous crucial biological processes in the human body. The ability to image the function of Zn2+ would be a significant asset to biomedical research for monitoring various physiopathologies dependent on its fate. To this end, we developed a novel Gd3+ chelate that can selectively recognize Zn2+ over other abundant endogenous metal ions and alter its paramagnetic properties. More specifically, this lanthanide chelate displayed an extraordinary increase in longitudinal relaxivity (r1) of over 400 % upon interaction with Zn2+ at 7 T and 25 °C, which is the greatest r1 enhancement observed for any of the metal ion‐responsive Gd‐based complexes at high magnetic field. A “turn‐on” mechanism responsible for these massive changes was confirmed through NMR and luminescence lifetime studies on a 13C‐labeled Eu3+ analogue. This molecular platform represents a new momentum in developing highly suitable magnetic resonance imaging contrast agents for functional molecular imaging studies of Zn2+.

Highly Potent MRI Contrast Agent Displaying Outstanding Sensitivity to Zinc Ions.

Zinc ions play an important role in numerous crucial biological processes in the human body. The ability to image the function of Zn2+ would be a significant asset to biomedical research for monitoring various physiopathologies dependent on its fate. To this end, we developed a novel Gd3+ chelate that can selectively recognize Zn2+ over other abundant endogenous metal ions and alter its paramagnetic properties. More specifically, this lanthanide chelate displayed an extraordinary increase in longitudinal relaxivity (r 1) of over 400 % upon interaction with Zn2+ at 7 T and 25 °C, which is the greatest r 1 enhancement observed for any of the metal ion‐responsive Gd‐based complexes at high magnetic field. A “turn‐on” mechanism responsible for these massive changes was confirmed through NMR and luminescence lifetime studies on a 13C‐labeled Eu3+ analogue. This molecular platform represents a new momentum in developing highly suitable magnetic resonance imaging contrast agents for functional molecular imaging studies of Zn2+.

Molecular-level insights into structure and dynamics in ionic liquids and polymer gel electrolytes

Designing new electrolytes requires a better understanding of the correlation between their transport properties and their molecular structure. In this work, we present a detailed study of ionic liquids and polymer gel electrolytes probing their structure and dynamics by nuclear magnetic resonance (NMR) spectroscopy. In particular, ammonium- and phosphonium-based ionic liquids (ILs) are combined with different LiTFSI concentrations, and then with different ratios of poly(methylmethacrylate) polymer. The temperature dependence of self-diffusion coefficients of mobile species, DLi+, DTFSI- and DP4441+ or DN4441+, measured by pulsed field gradient (PFG) NMR spectroscopy obeys the Arrhenius equation. Diffusivity of [P4441][TFSI] ILs is found to be greater than those of the [N4441][TFSI] ILs in both liquid and gel electrolytes. Solid state NMR experiments including 13C and 19F MAS, 13C{19F},13C{1H} CPMAS probe the local structure and molecular-level interactions between ions and polymer in gel electrolytes, particularly for samples with higher PMMA content (≥25 wt%). Finally, the fast field cycling relaxometry has been used to unveil the rotational and translational dynamics of P4441+ or N4441+ and TFSI− by measuring 1H and 19F R1 relaxation rate profiles at different temperatures. A comprehensive NMR analysis including relaxation studies at low magnetic field provides decisive new insights regarding the formation of ionic clusters and the interaction of ions with the polymer chain in the case of the gel electrolytes.

TEA-assistant synthesis of MOF-74 nanorods for drug delivery and in-vitro magnetic resonance imaging

Zn-MOF-74 nanorods with uniform diameters of about 200 nm were successfully prepared by a triethylamine (TEA) assistant solvothermal method. The effects of TEA on the sizes and morphologies of nanoscale particles were investigated. Guided by this method, bimetallic ZnxMn1-x-MOF-74s were facilely prepared to endow the nanomaterial with magnetic resonance imaging (MRI) ability. Nanoscale Zn0.7Mn0.3-MOF-74 were successfully produced with homogenous Mn dispersion. Magnetic resonance relaxivity studies using clinical MRI equipment proved that Zn0.7Mn0.3-MOF-74 nanoparticles show a satisfactory r1 relaxivity value of 6.5 mM−1 s−1. The saturated DOX loading capacity of Zn0.7Mn0.3-MOF-74 nanocarriers was evaluated to 113 mg g−1. After chitosan (CS) coating, cytotoxicity experiments showed that [email protected]0.7Mn0.3[email protected] nanocomposites featured adequate biotolerability and no interference with cellular metabolism. These results indicated great potential of the bimetallic ZnMn-MOF-74s as new biomedical materials integrating cellular drug delivery with MR imaging applications.

Multifunctional Core-Shell Tecto Dendrimers Incorporated with Gold Nanoparticles for Targeted Dual Mode CT/MR Imaging of Tumors.

Development of multifunctional nanoprobes with an excellent imaging performance for precision tumor imaging still remains a great challenge. Here, we report the creation of multifunctional core-shell tecto dendrimers (CSTDs) incorporated with gold nanoparticles (Au NPs) as a platform for dual-mode computed tomography (CT)/magnetic resonance (MR) imaging of tumors. In this work, β-cyclodextrin (CD)-modified generation 5 poly(amidoamine) (PAMAM) dendrimers were synthesized and entrapped with Au NPs as the core. Then, adamantine (Ad)-modified generation 3 PAMAM dendrimers acted as a shell to form Au NP-entrapped CSTDs (for short, Au CSTDs) through supramolecular host-guest recognition between CD and Ad. The formed Au CSTDs were sequentially modified with Arg-Gly-Asp (RGD) peptide through a spacer of polyethylene glycol (PEG), Gd chelator, and 1,3-propane sultone, followed by chelating Gd (III) ions. The synthesized multifunctional Au CSTDs with a mean size of 11.61 nm possess good colloidal stability, high X-ray attenuation property and high r1 relaxivity (9.414 mM-1 s-1), good antifouling property, and desired cytocompatibility. Due to the RGD-mediated targeting specificity to αvβ3 integrin-overexpressing cancer cells, the multifunctional Au CSTDs enable targeted CT/MR dual mode imaging of a breast cancer model in vivo and can be cleared out of body through metabolization pathway with good biosafety profile. The developed multifunctional CSTDs may be applied as an effective CT/MR dual mode imaging probe for accurate diagnosis of various αvβ3 integrin-overexpressing cancer types.

Structure-Relaxivity Mechanism of an Ultrasmall Ferrite Nanoparticle T1 MR Contrast Agent: The Impact of Dopants Controlled Crystalline Core and Surface Disordered Shell.

Ultrasmall ferrite nanoparticles (UFNPs) have emerged as powerful magnetic resonance imaging (MRI) T1 nanoprobe for noninvasive visualization of biological events. However, the structure-relaxivity relationship and regulatory mechanism of UFNPs remain elusive. Herein, we developed chemically engineered 3.8 nm ZnxFe3-xO4@ZnxMnyFe3-x-yO4 (denoted as ZnxF@ZnxMnyF) nanoparticles with precise dopants control in both crystalline core and disordered shell as a model system to assess the impact of dopants on the relaxometric properties of UFNPs. It is determined that the core-shell dopant architecture allows the optimal tuning of r1 relaxivity for Zn0.4F@Zn0.4Mn0.2F up to 20.22 mM-1 s-1, which is 5.2-fold and 6.5-fold larger than that of the original UFNPs and the clinically used Gd-DTPA. Moreover, the high-performing UFNPs nanoprobe, when conjugated with a targeting moiety AMD3100, enables the in vivo MRI detection of small lung metastasis with greatly enhanced sensitivity. Our results pave the way toward the chemical design of ultrasensitive T1 nanoprobe for advanced molecular imaging.

MnAl-Layered Double Hydroxide Nanosheets Infused with Fluorouracil for Cancer Diagnosis and Therapy

Nanotheranostic materials with a layered double hydrotalcite (LDH) structure, containing manganese as a contrast agent for MRI and fluorouracil (FU) as a model anticancer drug, were prepared. The manganese was rationally included in the two-dimensional (2D) LDH construction by co-precipitation (CP) at low suprasaturation at a theoretic Mn/Al ratio of 2. The anticancer drug was strategically introduced in the layered solid by two synthetic approaches, that is, CP at low suprasaturation and CP coupled with ion exchange (IE). The materials were extensively characterized for their composition, structure, texture, morphology, and oxidation state by AAS, XRD, N2 physisorption, FT-IR, SEM, TEM, TGA, DR UV−vis, and XPS. The results of physicochemical characterization revealed high-quality 2D materials in which manganese mainly exists as Mn2+ and Mn3+ while the mass loading of FU was 6.96 and 5.28% for the samples prepared by CP and CP coupled with IE, respectively. The nanomaterials exhibited high r1 and r2 relaxivities, particularly at pH = 7.4. The mathematical models used to fit the experimental data revealed a quasi-Fickian diffusion of the FU release from MnAl-LDH.

Versatile Surface Functionalization of Water-Dispersible Iron Oxide Nanoparticles with Precisely Controlled Sizes.

The synthesis of highly water-dispersible iron oxide nanoparticles with surface functional groups and precisely controlled sizes is essential for biomedical application. In this paper, we report a one-pot strategy for versatile surface functionalization. The iron oxide nanoparticles are first synthesized by thermal decomposition of iron(III) acetylacetonate (Fe(acac)3) in diethylene glycol (DEG), and their surfaces are modified by adding the surface ligands at the end of the reaction. The size of iron oxide nanoparticles can be precisely controlled in nanometer scale by continuous growth. This facile synthesis method enables the surface modification with different coating materials such as dopamine (DOPA), polyethylene glycol with thiol end group (thiol-PEG), and poly(acrylic acid) (PAA) onto the iron oxide nanoparticles, introducing new surface functionalities for future biomedical application. From transmission electron microscopy (TEM) and X-ray diffraction (XRD), the morphology and crystal structure are not changed during surface functionalization. The attachment of surface ligands is studied by Fourier transform infrared spectroscopy (FTIR) and Thermogravimetric Analysis (TGA). The surface functional groups are confirmed by X-ray Photoelectron Spectroscopy (XPS). In correlation with the change of hydrodynamic size, PAA coated nanoparticles are found to exhibit outstanding stability in aqueous solution. Furthermore, we demonstrate that the functional groups are available for conjugating with other molecules such as fluorescent dye, showing potential biological applications. Lastly, the magnetic resonance phantom studies demonstrate that iron oxide nanoparticles with PAA coating can be used as T1 and T2 dual-modality contrast agents. Both r1 and r2 relaxivities significantly increase after surface functionalization with PAA, indicating improved sensitivity.

Mn-based 2D layered nanomaterials for boosting the MRI signal

Manganese-based 2D nanoparticles with increased longitudinal relaxivity (r1) in MRI were synthesised by co-precipitation at low suprasaturation. The results of physico-chemical characterizations, i.e., XRD, FT-IR, DR UV–vis, N2 physisorption, and SEM, showed an excellent 2D nanomaterial in which manganese is predominantly incorporated as Mn2+ and Mn3+. The r1 relaxivity obtained on a 1.0 Tesla apparatus at pH = 7.4 is significantly improved (r1 = 1.298 mM−1 s−1) as compared with other similar layered materials containing manganese.

Exploring the Unique Contrast Properties of Aptamer-Gadolinium Conjugates in Magnetic Resonance Imaging for Targeted Imaging of Thrombi.

Objective: An important clinical question in the determination of the extent of thrombosis-related vascular conditions is the identification of blood clot location. Fibrin is a major molecular constituent of blood clots and can, therefore, be utilized in molecular imaging. In this proof-of-concept study, we sought to prepare a fibrin-targeting magnetic resonance imaging contrast agent, using a Gd(III)-loaded fibrinogen aptamer (FA) chelate conjugate (Gd(III)-NOTA-FA) (NOTA = 1,4,7-triazacyclononane-1,4,7-triacetic acid), to endow the ability to specifically accumulate at the location of blood clots, thereby enhancing contrast capabilities. Methods: The binding affinity of FA for fibrin was confirmed by fluorescence microscopy and microscale thermophoresis. The preparation and effective loading of the chelate-aptamer conjugates were confirmed by mass spectrometry and a xylenol orange colorimetric test. Longitudinal and transverse relaxivities and the effects of target binding were assessed using T1- and T2-map sequences at 7 T. T1- and T2-weighted images were acquired after blood clots were treated with Gd(III)-NOTA-FA. Collagen was used as the protein control, while an unrelated aptamer sequence, FB139, was used as the aptamer control. Results: FA demonstrated a high affinity and selectivity toward the polymeric protein, with a Kd of 16.6 nM, confirming an avidity over fibrinogen. The longitudinal (r1) and transverse (r2) relaxivities of Gd(III)-NOTA-FA demonstrated that conjugation to the long aptamer strand shortened T1 relaxation times and increased T2 relaxation times (3.04 and 38.7 mM-1 s-1, respectively). These effects were amplified by binding to the fibrin target (1.73 and 46.5 mM-1 s-1, respectively). In vitro studies with thrombin-polymerized human blood (clots) in whole blood showed an unexpected enhancement of signal intensity (hyperintense) produced exclusively at the location of the clot during the T2-weighted scan, while the presence of fibrinogen within a whole blood pool resulted in T1 signal intensity enhancement throughout the pool. This is advantageous, as simply reversing the type of a scan from a typical T1-weighted to a T2-weighted would allow to selectively highlight the location of blood clots. Conclusions: Gd(III)-NOTA-FA can be used for molecular imaging of thrombi, through fibrin-targeted delivery of contrast to the location of blood clots in T2-weighted scans.

Controllable synthesis of exceptionally small-sized superparamagnetic magnetite nanoparticles for ultrasensitive MR imaging and angiography.

The superparamagnetic magnetite nanoparticles have broad application prospects in the diagnosis and treatment of cancer. Herein, a series of monodispersed exceptionally small-sized superparamagnetic magnetite nanoparticles (ESM NPs) with tunable size were synthesized through thermal decomposition of an iron precursor by simply changing the reaction temperature and stabilizing agents. The underlying mechanisms of regulating the size and properties of ESM NPs were studied. The surface of hydrophobic ESM NPs was modified with a carboxyl-polyethylene glycol-phosphoric acid ligand, and the obtained water-soluble ESM NPs showed extremely high long-term stability under various aqueous environments and physiological conditions. The hemolysis and cytotoxicity evaluations showed that the ESM NPs had good blood compatibility and no obvious cytotoxicity. The 2.3 nm ESM NPs exhibited an extremely high longitudinal relaxivity (r1) of 6.0 mM-1 s-1, which was higher than that of the clinical gadolinium complex contrast agent (r1 = 3.8 mM-1 s-1), and had an appropriate r2/r1 ratio of 4.0. The in vivo results showed that the nanoparticles exhibited superior contrast effects in both T1 and T2 MR imaging, as well as high-resolution contrast in MR angiography. This study provides a general strategy for the controlled synthesis of ESM NPs and reveals the size and property regulation mechanisms, which undoubtedly provides the possibility of designing highly sensitive MR imaging probes based on small-sized magnetic nanoparticles for clinical diagnostic applications.

Silica-Coated Fe3O4 Nanoparticles as a Bifunctional Agent for Magnetic Resonance Imaging and ZnII Fluorescent Sensing.

Bifunctional magnetic/fluorescent core-shell silica nanospheres (MNPs) encapsulated with the magnetic Fe3O4 core and a derivate of 8-amimoquinoline (N-(quinolin-8-yl)-2-(3-(triethoxysilyl) propylamino) acetamide) (QTEPA) into the shell were synthesized. These functional MNPs were prepared with a modified stöber method and the formed Fe3O4@SiO2-QTEPA core-shell nanocomposites are biocompatible, water-dispersible, and stable. These prepared nanoparticles were characterized by X-ray power diffraction (XRD), transmission electron microscopy (TEM), thermoelectric plasma Quad II inductively coupled plasma mass spectrometry (ICP-MS), superconducting quantum interference device (SQUID), TG/DTA thermal analyzer (TGA) and Fourier transform infrared spectroscopy (FTIR). Further application of the nanoparticles in detecting Zn2+ was confirmed by the fluorescence experiment: the nanosensor shows high selectivity and sensitivity to Zn2+ with a 22-fold fluorescence emission enhancement in the presence of 10 μM Zn2+. Moreover, the transverse relaxivity measurements show that the core-shell MNPs have T2 relaxivity (r2) of 155.05 mM−1 S−1 based on Fe concentration on the 3.0 T scanner, suggesting that the compound can be used as a negative contrast agent for MRI. Further in vivo experiments showed that these MNPs could be used as MRI contrast agent. Therefore, the new nanosensor provides the dual modality of magnetic resonance imaging and optical imaging.

A T2ex MRI Dy-based contrast agent for direct pH imaging using a ratiometric approach.

pH is a critical parameter that has found unique application in magnetic resonance imaging (MRI) mapping acidity in tissues. This study reports a series of Dy-based MR probes that show innovative T2ex features, governed by proton catalyzed events. With an increase of pH from 5.5 to 8.0, the r2ex relaxivity increased dramatically, while the r1 relaxivity remained unchanged. The resulting r2ex/r1 allowed for concentration-independent and direct mapping of physiologically relevant pH ranges.

Biomineralized iron oxide-polydopamine hybrid nanodots for contrast-enhanced T1-weighted magnetic resonance imaging and photothermal tumor ablation.

Iron oxide nanoparticles (IO NPs) have become the focus of molecular imaging probes for contrast enhanced magnetic resonance (MR) imaging due to their intrinsic magnetic and biodegradable properties, as well as long blood half-lives and low toxicity. Massive efforts have been made to explore the IO NPs as T2-weighted MR contrast agents, which have high susceptibility to induce a long-range magnetic field that interferes with diagnosis. Thus, the development of IO NPs with potent T1 relaxivity might help in providing an alternative for clinically applied gadolinium chelates. Herein, biomineralized iron oxide-polydopamine hybrid nanodots (IO/PDA-NDs) have been constructed using albumin as the nanoreactors to induce nanoprecipitation and polymerization simultaneously, facilitating T1-weighted contrast-enhancement as well as photothermal therapeutic capability. The IO nanoclusters in IO/PDA-NDs have an r1 relaxivity of 5.79 mM-1 s-1 with a relatively low r2/r1 ratio of 1.71, demonstrating the preferable iron oxide based T1 contrast agents. The high photothermal conversion coefficient and tumor targeting effect of the hybrid nanodots could result in complete tumor ablation efficacy. The biomineralization method provides a promising approach for the integration of tumor diagnosis and treatment to achieve efficient cancer theranostics.

Pyclen-based Gd complex with ionisable side-chain as a contrastophore for the design of hypersensitive MRI nanoprobes: Synthesis and relaxation studies

A straightforward method for synthesizing at the multigram scale a low molecular weight PCTA-based gadolinium complex bearing an ionizable oxyacetic chain on the pyridine unit was described, together with its encapsulation within a nanohydrogel matrix. The ionic gelation occurred between chitosan and hyaluronic acid, reinforced by crosslinking with sodium tripolyphosphate. The resulting nanogels are spherical and narrowly monodisperse. They are stable for at least four months at room temperature in water and in media of higher ionic strength (NaCl 0.9%, PBS). They display an enhanced longitudinal relaxivity r1 of 15.9 and 12.1 mM−1.s−1 at 20 MHz and 60 MHz at 37 °C respectively which is at least 4 times higher than that of DOTAREM®.

Predicting 1H NMR relaxation in Gd3+-aqua using molecular dynamics simulations.

Atomistic molecular dynamics simulations are used to predict 1H NMR T1 relaxation of water from paramagnetic Gd3+ ions in solution at 25 °C. Simulations of the T1 relaxivity dispersion function r1 computed from the Gd3+-1H dipole-dipole autocorrelation function agree within ≃8% of measurements in the range f0 ≃ 5 ↔ 500 MHz, without any adjustable parameters in the interpretation of the simulations, and without any relaxation models. The simulation results are discussed in the context of the Solomon-Bloembergen-Morgan inner-sphere relaxation model, and the Hwang-Freed outer-sphere relaxation model. Below f0 ≲ 5 MHz, the simulation overestimates r1 compared to measurements, which is used to estimate the zero-field electron-spin relaxation time. The simulations show potential for predicting r1 at high frequencies in chelated Gd3+ contrast-agents used for clinical MRI.

Binding site exchange kinetics revealed through efficient spin-spin dephasing of hyperpolarized 129Xe.

Spin exchange between different chemical environments is an important observable for characterizing chemical exchange kinetics in various contexts, including protein folding, chelation chemistry, and host–guest interactions. Such spins experience effective spin–spin relaxation rate, R2,eff, that typically shows a dispersive behavior which requires detailed analysis. Here, we describe a class of highly simplified R2,eff behavior by relying on hyperpolarized 129Xe as a freely exchanging ligand reporter. It provides large chemical shift separations that yield reduced expressions of both the Swift–Connick and the Carver–Richards treatment of exchange-induced relaxation. Despite observing a diamagnetic system, R2,eff is dominated by large Larmor frequency jumps and thus allows detection of otherwise inaccessible analyte concentrations with a single spin echo train (only 0.01% of the overall hyperpolarized spins need to be transiently bound to the molecule). The two Xe hosts cryptophane-A monoacid (CrA-ma) and cucurbit[6]uril (CB6) represent two exemplary families of container molecules (the latter one also serving as drug delivery vehicles) that act as highly efficient phase shifters for which we observed unprecedented exchange-induced relaxivity r2 (up to 866 s−1 mM−1). By including methods of spatial encoding, multiple data points can be collected simultaneously to isolate the exchange contribution and determine the effective exchange rate in partially occupied binding sites with a single delivery of hyperpolarized nuclei. The relaxivity is directly related to the guest turnover in these systems and temperature-dependent measurements yield an activation energy of EA = 41 kJ mol−1 for Xe@CrA-ma from simple relaxometry analysis. The concept is transferable to many applications where Xe is known to exhibit large chemical shifts.