Table 1.
Summary of relaxivity responses to various environmental stimuli of molecular, macromolecular, polymeric and particulate MRI CAs
| Responsive MRI probe | Stimulus | Mechanistic change | r1 switch [mM−1 s−1] | Percentage change | Ref. |
|---|---|---|---|---|---|
| Molecular MRI CAs | |||||
| 4,7,10-Tri(acetic acid)-1-(2-β-galactopyranosylethoxy)- 1,4,7,10-tetraazacyclododecane gadolinium (EGad) |
β-Galactosidase | q | Not reported | 20% decrease | 28 |
| (l-(2-(β-Glalactopyranosyloxy)propyl) -4,5,10-tris(carboxymethyl-1,4,7,10-tetra- azacyclododecane))gadolinium (EGadMe) |
β-Galactosidase | q | 0.90–2.72 s−1 a at 500 MHz | 200% increase | 29 |
| Gd–DO3A bearing a pendant β-glucuronic acid moiety connected by a self-immolative linker |
β-Glucuronidase | q | 4.75–3.90 at 60 MHz | 20% decrease | 30 |
| Gd–DO3A appended with acetoxymethyl esters | Porcine liver esterase |
q | 5.7–10.8 at 20 MHz | 89% increase | 32 |
| Bis-5-hydroxytryptamide-diethylenetriamine-pentatacetate gadolinium (MPO–Gd) |
Myeloperoxidase (MPO) |
τ R | Not reported | Not reported | 27 |
| Gd–DTPA with phosphonate side chain (MS-325) | Human serum albumin (HSA) |
τ R | 5.6–50.8 at 20 MHz | 800% increase at 20 MHz | 33 |
| 5.0–25.0 at 64 MHz | 400% increase at 64 MHz | ||||
| Gd–DTPA appended with lysine residues | Thrombin-activa- table fibrinolysis inhibitor (TAFI) |
τ R | 12.5–25.2 at 20 MHz | 100% increase | 34 |
| Gd–DOTA with pendant diphenylphosphinamide groups | Human serum albumin (HSA) |
τ R | 7.3–16.0 at 20 MHz | 119% increase | 36 |
| Gd–DO3A–glutamate | Glutamic acid decarboxylase (GAD) |
q, τR | 8.0–11.5 at 20 MHz | 44% increase | 31 |
| Peptide-labelled GdDO3A (Gd3+–G80BP) | Ga180 protein | τ R | 8.3–44.8 at 20 MHz | 440% increase | 35 |
| Gd–DTPA bisamide | Zn2+ | q | 6.06–3.98 at 300 MHz | 34% decrease | 39 |
| Gd–DTPA bisamide | Zn2+ | q | 4.8–3.5 at 300 MHz | 27% decrease | 40 |
| Gd–DTPA-appended β-diketone (KMR–Mg) | Mg2+ (also Ca2+) | q | 4.98–3.95 at 20 MHz | 21% decrease | 41 |
| Gd–DOTA appended with N,N-bis(2-pyridyl-methyl) ethylene diamine (bisBPEN) diamide | Zn2+, Cu2+ | k ex | 5.0–6.0 at 23 MHz | 20% increase | 42 |
| Gd–DOTA appended with two bis-(3-pyrazolyl) units | Zn2+, Cu2+ | k ex | 4.2–6.9 at 23 MHz | 64% increase | 43 |
| Gd–diaminoacetate with 3 methylenes (Gd–daa3) | Zn2+ | q | 2.3–5.1 at 60 MHz | 121% increase | 44, 45 |
| Gd[l,2-bis[{[({l-[l,4,7-tris(carboxymethyl)-1,4,7,10-tetra- azacyclododecane-10-yl]eth-2-yl}amino)carbonyl]methyl}- (carboxymethyl)amino]ethane] |
Ca2+ | q | 5.4–7.1 at 500 MHz | 32% increase | 46 |
| Ethylene glycol tetraacetic acid (EGTA) linked to 2 Gd–DO3A chelates |
Ca2+ | q | 3.44–6.29 at 500 MHz | 83% increase | 47 |
| DOPTA–Gd | Ca2+ | q | 3.26–5.76 at 500 MHz | 80% increase | 48 |
| Gd–DO3A chelate with pyro-EGTA moiety | Ca2+, Zn2+ | q | 3.8–6.6 at 60 MHz | 73% increase | 55 |
| Gd–DO3A with a pendant iminodiacetate | Cu2+ | q | 3.76–5.29 at 400 MHz | 41% increase | 49 |
| Gd–DO3A with tethered thioether groups | Cu2+ | q | 1.5–6.9 at 20 MHz | 360% increase | 50 |
| Octaarginine-conjugated Gd–DO3A with tethered thioether groups | Cu+ | q | 3.9–12.5 at 60 MHz | 220% increase | 52 |
| Gd–DO3A with appended 8-amidequinoline (Gd-QDOTAMA) | Cu2+ | q | 4.27–7.29 at 400 MHz | 71% increase | 53 |
| Tryptophan-appended Gd–TTDA [Gd(Try-TTDA)(H2O)]2− | Cu2+ | q | 4.22–7.42 at 20 MHz | 76% increase | 54 |
| Di-metallic-DO3A with piperazine bridge | Hg2+ | q | 8.3–10.3 at 30 MHz | 24% increase | 51 |
| GdDOTA–diBPEN | Zn2+ | τ R | 5.0–17.5 at 23 MHz | 250% increase | 57 |
| Gd(phen)HDO3A chelate | Fe2+ | τ R | 3.7–12.2 at 20 MHz | 230% increase | 11 |
| [Gd2bpy(DTTA)2(H2O)4]2− | Fe2+ | τ R | 12.44–20.17 at 20 MHz | 62% increase | 59 |
| Terpyridine–Gd3+ chelate | pH | q | 12.8–2.0 at 20 MHz | 84% | 66 |
| [Gd(DOTA tetrakis(methylamide))]3+ | pH | τ m | 2.5–5.7 at 20 MHz | 128% | 22, 23 |
| Dinitrospiropyran–GdDO3A | NADH | q | 2.51–1.86 at 60 MHz | 26% decrease | 74, 75 |
| Spiropyran–GdDO3A | NADH | q | 5.58–8.60 at 60 MHz | 54% increase | 74 |
| Spiropyran–GdDO3A | Light | q | 3.72–2.93 at 60 MHz | 21% decrease | 75 |
| Macromolecular, polymeric and particulate MRI CAs | |||||
| G5-PAMAM dendrimer with Gd-complexes bearing phosphonate pendant arms |
pH | τR, τm | 10.8–24.0 at 20 MHz | 122% | 134 |
| Large unilamellar vesicles (POPC/DPPC) loaded with the an amphiphilic GdDO3A derivative |
pH | τR, τm | 4.5–13.5 at 43 MHz | 200% | 135 |
| Sulfonamide arm containing Gd-chelate hosted by poly-β-cyclodextrin |
pH | q | 8–16 at 43 MHz | 100% | 128 |
| Diacylphosphatidylethanolamine/ dipalmitoylglycerosuccinate based enosome loaded with a GdDTPA-derivative |
pH | τ io | 2.3–0.7 at 20 MHz | 228% | 159 |
| Poly-l-ornithine | pH | τR, τm | 23.0–32.0 at 20 MHz | 39% | 131 |
| Methacrylic acid based polymer cross-linked by N,N′-methylenebisacrylamide |
pH | Swelling (τR) | Non-cross-linked polymer: 6.7–12.1 Cross-linked polymer: 13.6–28.0 at 20 MHz | 106% | 107 |
|
n-Octylamine modified poly(SM-EVE) polymer loaded with aminoethyl-modified GdDO3A |
pH | Electrostatic repulsion (high pH), hydrophobic interaction (low pH) (τR) |
8.0–9.0 at 20 MHz | 12% | 112 |
| Avidin conjugated to GdDOTA derivative with a phosphonate pendant arm |
pH | τR, q | 10.4–12.6 at 128 MHz | 21% | 160 |
| Ketal-based polymer with a GdDTPA derivative | pH | Polymer degradation (τR) |
8.2–3.8 at 64 MHz | 115% | 126 |
| Gadonanotubes | pH | Gd3+ loss | 40.0–133.0 at 64 MHz | 233% | 86 |
| Gadofullerenes | pH | Aggregation (τR) | 10.4–38.5 at 30–60 MHz | 270% | 161 |
| Manganese oxide nanoparticles | pH | Release of Mn2+ ions |
8.8–27.7 at 64 MHz | 215% | 162 |
| Manganese oxide functionalised mesoporous silica nanoparticle |
pH | Dissolution | 0.8–8.8 at 128 MHz | 1015% | 163 |
| GdDOTA doped mesoporous silica nanoparticles capped by streptavidin | Biotinylated BSA | τ m | 5.8–12.7 at 300 MHz | 219% increase | 111 |
| Hexanuclear gadolinium organic octahedron | Glucosamine | kex, q | 388.5–62.1 at 400 MHz | 526% decrease | 110 |
| Manganese loaded apoferritin | Melanin | Reduction, dissolution (τR) |
0.3–6.0 at 300 MHz | 1900% increase | 164 |
| DNA aptamer conjugated to streptavidin and GdDOTA |
Adenosine | Release of Gd-DNA strand (τR) |
12.2–9.2 at 60 MHz | 33% decrease | 149 |
| Liposome with incorporated amphiphilic GdDOTA covalently linked to a peptide sequence |
Metalloproteinase-2 | τ R | 8.9–7.5 at 60 MHz | 16% decrease | 152 |
| GdDOTA covalently coupled to a chemically modified peptide sequence bearing a cyano and 1,2-aminothiol group |
Furin | Reduction, self-assembly into nanoparticles (τR) |
6.0–13.2 at 64 MHz | 220% increase | 137 |
| Perthiolated β-cyclodextrin-based nanocapsules | Reductive/hypoxic environment |
Reduction, degradation (τR) |
15.2–8.2 at 70 MHz | 46% decrease | 136 |
| P(NIPAM)-co-P(AM) hydrogel nanoparticles cross-linked by a GdDTPA-derivative and loaded into solid lipid nanoparticles |
Temperature | kex, τio, τR | 12.4–8.6 at 300 MHz | 44% decrease | 145 |
| POEGMA-b-P(NIPAM-co-NBA-co-Gd) diblock copolymer | Temperature | k ex | 6.5–12.1 at 300 MHz | 86% increase | 165 |
| Liposomes loaded with Gd-complexes | Temperature | τ io | 1828–394 msb at 300 MHz | 364% decrease | 143 |
a
Relaxation rate provided in s−1.
b
Relaxation time provided in ms.