Tuning the Optical Properties of 2‐Thienylpyridyl Iridium Complexes through Carboranes and Anions

2‐Thienylpyridyl iridium(III) complexes containing an o‐, m‐, or p‐carboranylvinyl‐2,2′‐bipyridine ligand and various counteranions (denoted o ‐ PF₆ , m ‐ BF₄ , m ‐ PF₆ , m ‐ SbF₆ , m ‐ ClO₄ , m ‐ OTf , m ‐ NO₃ , m ‐ BPh₄ , m ‐ F , m ‐ Cl , and p ‐ PF₆ ) were synthesized by using C‐formyl carboranes as starting materials. The solid‐state structures of o ‐ PF₆ , m ‐ PF₆ , m ‐ ClO₄ , and m ‐ BF₄ showed that the cations form twisted cavities in which the anions are fixed by multiple hydrogen bonds. Anion–hydrogen interactions were investigated for nine m‐carborane‐based complexes with different counteranions. All carborane‐based iridium(III) complexes show similar phosphorescence yields in solution but significantly different emission in the solid state. Anion‐exchange titration and theoretical calculations revealed the relationships between structures and optical properties. The size of the anion and C?H ??? X anion–hydrogen bonds strongly influence the phosphorescence quantum yield in the solid state. In particular, the C_car?H ??? X hydrogen bonds between the carboranyl unit and the anion play an important role in solid‐state phosphorescence. Complex p ‐ PF₆ was successfully applied in phosphorescence‐lifetime bioimaging owing to its low toxicity and near‐infrared emission.     

Tetraamine‐Derived Bifunctional Chelators for Technetium‐99m Labelling: Synthesis,Bioconjugation and Evaluation as Targeted SPECT Imaging Probes for GRP‐Receptor‐Positive Tumours

Owing to its optimal nuclear properties, ready availability, low cost and favourable dosimetry, ^99mTc continues to be the ideal radioisotope for medical‐imaging applications. Bifunctional chelators based on a tetraamine framework exhibit facile complexation with Tc(V)O₂ to form monocationic species with high in vivo stability and significant hydrophilicity, which leads to favourable pharmacokinetics. The synthesis of a series of 1,4,8,11‐tetraazaundecane derivatives ( 01 – 06 ) containing different functional groups at the 6‐position for the conjugation of biomolecules and subsequent labelling with ^99mTc is described herein. The chelator 01 was used as a starting material for the facile synthesis of chelators functionalised with OH ( 02 ), N₃ ( 04 ) and O‐succinyl ester ( 05 ) groups. A straightforward and easy synthesis of carboxyl‐functionalised tetraamine‐based chelator 06 was achieved by using inexpensive and commercially available starting materials. Conjugation of 06 to a potent bombesin‐antagonist peptide and subsequent labelling with ^99mTc afforded the radiotracer ^99mTc‐N4‐BB‐ANT, with radiolabelling yields of >97 % at a specific activity of 37 GBq μmol^?1. An IC₅₀ value of (3.7±1.3) nM was obtained, which confirmed the high affinity of the conjugate to the gastrin‐releasing‐peptide receptor (GRPr). Immunofluorescence and calcium mobilisation assays confirmed the strong antagonist properties of the conjugate. In vivo pharmacokinetic studies of ^99mTc‐N4‐BB‐ANT showed high and specific uptake in PC3 xenografts and in other GRPr‐positive organs. The tumour uptake was (22.5±2.6) % injected activity per gram (% IA g^?1) at 1 h post injection (p.i.). and increased to (29.9±4.0) % IA g^?1 at 4 h p.i. The SPECT/computed tomography (CT) images showed high tumour uptake, clear background and negligible radioactivity in the abdomen. The promising preclinical results of ^99mTc‐N4‐BB‐ANT warrant its potential candidature for clinical translation.     

Luminescence Properties of C‐Diazaborolyl‐ortho‐Carboranes as Donor–Acceptor Systems

Seven derivatives of 1,2‐dicarbadodecaborane (ortho‐carborane, 1,2‐C₂B₁₀H₁₂) with a 1,3‐diethyl‐ or 1,3‐diphenyl‐1,3,2‐benzodiazaborolyl group on one cage carbon atom were synthesized and structurally characterized. Six of these compounds showed remarkable low‐energy fluorescence emissions with large Stokes shifts of 15100–20260 cm^?1 and quantum yields (Φ_F) of up to 65 % in the solid state. The low‐energy fluorescence emission, which was assigned to a charge‐transfer (CT) transition between the cage and the heterocyclic unit, depended on the orientation (torsion angle, ψ) of the diazaborolyl group with respect to the cage C? C bond. In cyclohexane, two compounds exhibited very weak dual fluorescence emissions with Stokes shifts of 15660–18090 cm^?1 for the CT bands and 1960–5540 cm^?1 for the high‐energy bands, which were assigned to local transitions within the benzodiazaborole units (local excitation, LE), whereas four compounds showed only CT bands with Φ_F values between 8–32 %. Two distinct excited singlet‐state (S₁) geometries, denoted S₁(LE) and S₁(CT), were observed computationally for the benzodiazaborolyl‐ortho‐carboranes, the population of which depended on their orientation (ψ). TD‐DFT calculations on these excited state geometries were in accord with their CT and LE emissions. These C‐diazaborolyl‐ortho‐carboranes were viewed as donor–acceptor systems with the diazaborolyl group as the donor and the ortho‐carboranyl group as the acceptor.     

Pd0‐Mediated Rapid Cross‐Coupling Reactions,the Rapid C‐[11C]Methylations,Revolutionarily Advancing the Syntheses of Short‐Lived PET Molecular Probes

Positron emission tomography is a noninvasive method for monitoring drug (or diagnostic) behavior and its localization on the target molecules in the living systems, including the human body, using a short‐lived positron‐emitting radionuclide. New methodologies for introducing representative short‐lived radionuclides, ¹¹C and ¹⁸F, into the carbon frameworks of biologically active organic compounds have been established by developing rapid C‐[¹¹C]methylations and C‐[¹⁸F]fluoromethylations using rapid Pd⁰‐mediated cross‐coupling reactions between [¹¹C]methyl iodide (sp³‐hybridized carbon) and an excess amount of organotributylstannane or organoboronic acid ester having sp²(phenyl, heteroaromatic, or alkenyl), sp(alkynyl), or sp³(benzyl and cinnamyl)‐hybridized carbons; and [¹⁸F]fluoromethyl halide (iodide or bromide) and an organoboronic acid ester, respectively. These rapid reactions provide a firm foundation for an efficient and general synthesis of short‐lived ¹¹C‐ or ¹⁸F‐labeled PET molecular probes to promote in vivo molecular imaging studies.     

Carbon‐11 Radiolabelling of Organosulfur Compounds: 11C Synthesis of the Progesterone Receptor Agonist Tanaproget

Herein a new ¹¹C radiolabelling strategy for the fast and efficient synthesis of thioureas and related derivatives using the novel synthon, ¹¹CS₂, is reported. This approach has enabled the facile labelling of a potent progesterone receptor (PR) agonist, [¹¹C]Tanaproget, by the intramolecular reaction of the acyclic aminohydroxyl precursor with ¹¹CS₂, which has potential applications as a positron emission tomography radioligand for cancer imaging.     

Recent Progress in the Development of Solid‐State Luminescent o‐Carboranes with Stimuli Responsivity

o‐Carborane, a cluster compound containing boron and adjacent carbon atoms, displays intriguing luminescent properties. Recently, compounds containing o‐carborane units were found to show suppressed aggregation‐induced quenching and intense solid‐state emission; they also show potential for the development of stimuli‐responsive luminochromic materials. In this Minireview, we introduce three kinds of fundamental photochemical properties: aggregation‐induced emission, twisted intramolecular charge transfer in crystals, and environment‐sensitive excimer formation in solids. Based on these properties, several types of luminochromism, such as thermos‐, vapo‐, and mechanochromism, have been discovered. Based mainly on results from recent studies, we illustrate these mechanisms as well as unique luminescent behaviors of o‐carborane derivatives.     

Synthesis of 18F‐Labelled β‐Lactams by Using the Kinugasa Reaction

Owing to their broad spectrum of biological activities and low toxicity, β‐lactams are attractive lead structures for the design of novel molecular probes. However, the synthesis of positron emission tomography (PET)‐isotope‐labelled β‐lactams has not yet been reported. Herein, we describe the simple preparation of radiofluorinated β‐lactams by using the fast Kinugasa reaction between ¹⁸F‐labelled nitrone [¹⁸F]‐ 1 and alkynes of different reactivity. Additionally, ¹⁸F‐labelled fused β‐lactams were obtained through the reaction of a cyclic nitrone 7 with radiofluorinated alkynes [¹⁸F]‐ 6 a , b . Radiochemical yields of the Kinugasa reaction products could be significantly increased by the use of different Cu^I ligands, which additionally allowed a reduction in the amount of precursor and/or reaction time. Model radiofluorinated β‐lactam‐peptide and protein conjugates ([¹⁸F]‐ 10 and ¹⁸F‐labelled BSA conjugate) were efficiently obtained in high yield under mild conditions (aq. MeCN, ambient temperature) within a short reaction time, demonstrating the suitability of the developed method for radiolabelling of sensitive molecules such as biopolymers.     

Manipulation of Phosphorescence Efficiency of Cyclometalated Iridium Complexes by Substituted o‐Carboranes

A series of [(C^N)₂Ir(acac)] complexes [{5‐(2‐R‐CB)ppy}₂Ir(acac)] ( 3 a – 3 g ; acac=acetylacetonate, CB=o‐carboran‐1‐yl, ppy=2‐phenylpyridine; R=H ( 3 a ), Me ( 3 b ), iPr ( 3 c ), iBu ( 3 d ), Ph ( 3 e ), CF₃C₆H₄ ( 3 f ), C₆F₅ ( 3 g )) with various 2‐R‐substituted o‐carboranes at the 5‐position in the phenyl ring of the ppy ligand were prepared. X‐ray diffraction studies revealed that the carboranyl C?C bond length increases with increasing steric and electron‐withdrawing effects from the 2‐R substituents. Although the absorption and emission wavelengths of the complexes are almost invariant to the change of 2‐R group, the phosphorescence quantum efficiency varies from highly emissive (Φ_PL≈0.80 for R=H, alkyl) to poorly emissive (R=aryl) depending on the 2‐R group and the polarity of the medium. Theoretical studies suggest that 1) the almost nonemissive nature of the 2‐aryl‐substituted complexes is mainly attributable to the large contribution to the LUMO in the S₁ excited state from an o‐carborane unit and 2) the variation in the C?C bond length between the S₀ and T₁ state structures increases with increasing steric (2‐alkyl) and electronic effects (2‐aryl) of the 2‐R substituent and the polarity of the solvent. The solution‐processed electroluminescence (EL) devices that incorporated 3 b and 3 d as emitters displayed higher performance than the device based on the parent [(ppy)₂Ir(acac)] complex. Along with the high phosphorescence efficiency, the bulkiness of the 2‐R‐o‐carborane unit is shown to play an important role in improving device performance.     

Iodinated ortho‐Carboranes as Versatile Building Blocks to Design Intermolecular Interactions in Crystal Lattices

The crystal structures of numerous iodinated ortho‐carboranes have been studied, which has revealed the diversity of intermolecular interactions that these substances can adopt in the solid state. The nature—mostly as it relates to hydrogen and/or halogen bonds—and relative strength of such interactions can be adjusted by selectively introducing substituents onto the cluster, thus enabling the rational design of crystal lattices. In this work we present the newly determined crystal structures of the following iodinated ortho‐carboranes: 9‐I‐1,2‐closo‐C₂B₁₀H₁₁, 4,5,7,8,9,10,11,12‐I₈‐1,2‐closo‐C₂B₁₀H₄, 3,4,5,6,7,8,9,10,11,12‐I₁₀‐1,2‐closo‐C₂B₁₀H₂, 1‐Me‐8,9,10,12‐I₄‐1,2‐closo‐C₂B₁₀H₇, 1,2‐Me₂‐8,9,10,12‐I₄‐1,2‐closo‐C₂B₁₀H₆, and 1,2‐Ph₂‐8,9,10,12‐I₄‐1,2‐closo‐C₂B₁₀H₆. Their 3D supramolecular organization has been thoroughly investigated and compared to similar previously published crystal structures. Such a systematic survey has allowed us to draw some general trends. C_c? H???I? B hydrogen bonds (C_c= cluster carbon atoms) appear to be significant in the growth of the crystal lattices of these compounds, given the acidity of hydrogen atoms bonded to C_c, and the polarization of B? I bonds. These hydrogen bonds can be disrupted by selectively blocking the positions next to C_c, that is, B(3) and B(6), with bulky substituents that prevent iodine atoms from approaching as hydrogen acceptors. Halogen bonds of the type B? I???I? B are frequently observed in most cases, thus suggesting that these interactions could be attractive in boron clusters. In addition, different substituents can be grafted onto the ortho‐carborane surface, thereby providing further possibilities for homomeric or heteromeric molecular assembly.     

Copper‐Mediated Aromatic Radiofluorination Revisited: Efficient Production of PET Tracers on a Preparative Scale

Two novel methods for copper‐mediated aromatic nucleophilic radiofluorination were recently reported. Evaluation of these methods reveals that, although both are efficient in small‐scale experiments, they are inoperative for the production of positron emission tomography (PET) tracers. Since high base content turned out to be responsible for low radiochemical conversions, a “low base” protocol has been developed which affords ¹⁸F‐labeled arenes from diaryliodonium salts and aryl pinacol boronates in reasonable yields. Furthermore, implementation of our “minimalist” approach to the copper‐mediated [¹⁸F]‐fluorination of (mesityl)(aryl)iodonium salts allows the preparation of ¹⁸F‐labeled arenes in excellent RCCs. The novel radiofluorination method circumvents time‐consuming azeotropic drying and avoids the utilization of base and other additives, such as cryptands. Furthermore, this procedure enables the production of clinically relevant PET tracers; [¹⁸F]FDA, 4‐[¹⁸F]FPhe, and [¹⁸F]DAA1106 are obtained in good isolated radiochemical yields. Additionally, [¹⁸F]DAA1106 has been evaluated in a rat stroke model and demonstrates excellent potential for visualization of translocator protein 18 kDa overexpression associated with neuroinflammation after ischemic stroke.     

Rhodium‐Catalyzed Regioselective Hydroxylation of Cage B−H Bonds of o‐Carboranes with O2 or Air

A rhodium‐catalyzed hydroxylation of a cage B4?H bond in o‐carboranes with either O₂ or air as the oxygen source is described, and serves as a new methodology for the regioselective generation of a series of 4‐OH‐o‐carboranes in a one‐pot process. The use of either O₂ or air as both the oxidant and the oxygen source makes this protocol very environmentally friendly and practical.     

A Convenient Approach To Synthesize o‐Carborane‐Functionalized Phosphorescent Iridium(III) Complexes for Endocellular Hypoxia Imaging

The structure–property relationship of carborane‐modified iridium(III) complexes was investigated. Firstly, an efficient approach for the synthesis of o‐carborane‐containing pyridine ligands a – f in high yields was developed by utilizing stable and cheap B₁₀H₁₀(Et₄N)₂ as the starting material. By using these ligands, iridium(III) complexes I – VII were efficiently prepared. In combination with DFT calculations, the photophysical and electrochemical properties of these complexes were studied. The hydrophilic nido‐o‐carborane‐based iridium(III) complex VII showed the highest phosphorescence efficiency (abs. =0.48) among known water‐soluble homoleptic cyclometalated iridium(III) complexes and long emission lifetime (τ=1.24 μs) in aqueous solution. Both of them are sensitive to O₂, and thus endocellular hypoxia imaging of complex VII was realized by time‐resolved luminescence imaging (TRLI). This is the first example of applying TRLI in endocellular oxygen detection with a water‐soluble nido‐carborane functionalized iridium(III) complex.     

Competition between Halogen,Hydrogen and Dihydrogen Bonding in Brominated Carboranes

Halogen bonds are a subset of noncovalent interactions with rapidly expanding applications in materials and medicinal chemistry. While halogen bonding is well known in organic compounds, it is new in the field of boron cluster chemistry. We have synthesized and crystallized carboranes containing Br atoms in two different positions, namely, bound to C‐ and B‐vertices. The Br atoms bound to the C‐vertices have been found to form halogen bonds in the crystal structures. In contrast, Br atoms bound to B‐vertices formed hydrogen bonds. Quantum chemical calculations have revealed that halogen bonding in carboranes can be much stronger than in organic architectures. These findings open new possibilities for applications of carboranes, both in materials and medicinal chemistry.     

Kinetics of Gallium Removal from Transferrin and Thermodynamics of Gallium-Binding by Sulfonated Tricatechol Ligands

Abstract

The thermodynamics of complexation of gallium by tricatechol ligand analogues of enterobactin and the kinetics of gallium removal from human serum transferrin (Tf) by one of those ligands have been studied by UV spectrophotometry. The ligands are a sulfonated monomeric catechoylamide, DMBS (N,N-dimethyl-2,3-dihydroxy-5-sulfonatobenzamide), and four sulfonated triscatechoylamides, MECAMS (1,3,5-N,N',N”-tris(5-sulfonato-2,3-dihydroxybenzoyl)-triaminomethylbenzene), Me₃MECAMS (N, N', N-trimethyl-MECAMS), 3,4-LICAMS (N, N', N”-tris(5-sulfonato-2,3-dihydroxybenzoyl)-1,5,10-triazadecane), and (DiP)LICAMS (N, N”-diisopropyl-LICAMS). The individual orthohydroxyl protonation constants are 7.15 (DMBS), and (average values for the three protons of the tricatechols) 7.09 (MECAMS), 7.01 (LICAMS), 7.62 (Me₃MECAMS), and 7.75 ((DiP(LICAMS), in good agreement with average values obtained potentiometrically. The overall formation constants for binding of Ga³⁺ by these ligands are β₁₁₃ = 41.9 for DMBS, β₁₁₀ = 41.1 for LICAMS, 36.6 for (DiP)-LICAMS, and 39.1 for Me₃MECAMS. Gallium is removed from the two metal binding sites of Ga₂Tf in a process by 3,4-LICAMS that is first order in both Tf and ligand at different rates (277M^?1 min^?1 and 17M^?1 min^?1). These are 12 and 3.4 times the corresponding rates of iron removal from Fe₂Tf. The dissociation pathways of the gallium-ligand complexes upon protonation of the ligands were probed by whole spectrum analysis with the non-linear least-squares program REFSPEC. For all three triscatechoylamide complexes, protonation occurs in sequential one-proton reactions wth logK MLH_n (n = 1, 2, 3) equal to 5.93, 5.00, 2.4 for MECAMS: 5.8, 5.7, 3.0 for 3,4-LICAMS; 6.81,6.34, 3.0 for Me₃MECAMS; 6.34, 6.33, 4.3 for (DiP)LICAMS. First- and second-derivative spectra show that for complexes of trimeric ligands the last two protonations result in a complex with a completely dissociated catecholate arm, Ga(cat)₂-catH₂, similar to the Ga(DMBS)₂ complex observed with the monomer. In the linear complexes, the middle ligand arm is detached from the metal first. Addition of a fourth proton resulted in decomposition of the gallium-trimeric ligand complex.     

Ortho‐Stabilized 18F‐Azido Click Agents and their Application in PET Imaging with Single‐Stranded DNA Aptamers

Azido ¹⁸F‐arenes are important and versatile building blocks for the radiolabeling of biomolecules via Huisgen cycloaddition (“click chemistry”) for positron emission tomography (PET). However, routine access to such clickable agents is challenged by inefficient and/or poorly defined multistep radiochemical approaches. A high‐yielding direct radiofluorination for azido ¹⁸F‐arenes was achieved through the development of an ortho‐oxygen‐stabilized iodonium derivative (OID). This OID strategy addresses an unmet need for a reliable azido ¹⁸F‐arene clickable agent for bioconjugation reactions. A ssDNA aptamer was radiolabeled with this agent and visualized in a xenograft mouse model of human colon cancer by PET, which demonstrates that this OID approach is a convenient and highly efficient way of labeling and tracking biomolecules.     

fac-[TcO3(tacn)]+: a versatile precursor for the labelling of pharmacophores, amino acids and carbohydrates through a new ligand-centred labelling strategy

Herein, we report a protocol for the synthesis of [(99m)TcO(3)(tacn)](+) ([1](+)) (tacn = 1,4,7-triazacyclononane) that is suitable for clinical translation. Bioconjugates containing pharmacophores ([TcO(NO(2)-Imi)(tacn)](+); [3](+)), artificial amino acids ([TcO(Fmoc-allyl-His)(tacn)](+); [5](+)), and glucose derivatives ([TcO(allyl-tetraacetylglucose)(tacn)](+); [7](+)) were synthesized by cycloaddition strategies and fully characterized ((99)Tc and (99m)Tc). These new technetium complexes are stable at neutral pH and demonstrate the potential and flexibility of the [3+2] cycloaddition labelling concept. In addition to the synthetic work, the first biodistribution studies of [1](+) and the small [3+2] cycloadduct [(99m)TcO(NO(2)-Imi)(tacn)](+) ([3](+)) were completed. The biodistribution studies suggest the stability of these complexes in vivo. Furthermore, it was demonstrated that the high hydrophilicity of the [(99m)TcO(3)(tacn)](+) building block is a complement to the complexes of the fac-{Tc(CO)(3)}(+) core.     

4‐Trifluoromethyl‐Substituted Coumarins with Large Stokes Shifts: Synthesis,Bioconjugates, and Their Use in Super‐Resolution Fluorescence Microscopy

Bright and photostable fluorescent dyes with large Stokes shifts are widely used as sensors, molecular probes, and light‐emitting markers in chemistry, life sciences, and optical microscopy. In this study, new 7‐dialkylamino‐4‐trifluoromethylcoumarins have been designed for use in bioconjugation reactions and optical microscopy. Their synthesis was based on the Stille reaction of 3‐chloro‐4‐trifluoromethylcoumarins and available (hetero)aryl‐ or (hetero)arylethenyltin derivatives. Alternatively, the acylation of 2‐trifluoroacetyl‐5‐dialkylaminophenols with available (hetero)aryl‐ or (hetero)arylethenylacetic acids followed by intramolecular condensation afforded coumarins with 3‐(hetero)aryl or 3‐[2‐(hetero)aryl]ethenyl groups. Hydrophilic properties were provided by the introduction of a sulfonic acid residue or by phosphorylation of a primary hydroxy group attached at C‐4 of the 2,2,4‐trimethyl‐1,2‐dihydroquinoline fragment fused to the coumarin fluorophore. For use in immunolabeling procedures, the dyes were decorated with an (activated) carboxy group. The positions of the absorption and emission maxima vary in the ranges 413–480 and 527–668 nm, respectively. The phosphorylated dye, 9 ,CH?CH‐2‐py,H, with the 1‐(3‐carboxypropyl)‐4‐hydroxymethyl‐2,2‐dimethyl‐1,2‐dihydroquinoline fragment fused to the coumarin fluorophore bearing the 3‐[2‐(2‐pyridyl)ethenyl] residue (absorption and emission maxima at 472 and 623 nm, respectively) was used in super‐resolution light microscopy with stimulated emission depletion and provided an optical resolution better than 70 nm with a low background signal. As a result of their large Stokes shifts, good fluorescence quantum yields, and adequate photostabilities, phosphorylated coumarins enable two‐color imaging (using several excitation sources and a single depletion laser) to be combined with subdiffractional optical resolution.     

Facial Synthesis of o‐Carborane‐Substituted Alkenes and Allenes by a Regioselective Ene Reaction of 1,3‐Dehydro‐o‐carborane

1,3‐Dehydro‐o‐carborane is a useful synthon for selective cage boron functionalization of o‐carboranes. It reacts readily with alkenes or alkynes to give a variety of cage B(3)‐alkenyl/allenyl o‐carboranes by ene reactions in very high yields and excellent regioselectivity. This can be ascribed to the highly polarized cage C?B multiple bond, which lowers the activation barriers of the ene reaction.     

Synthesis and Evaluation of GdIII‐Based Magnetic Resonance Contrast Agents for Molecular Imaging of Prostate‐Specific Membrane Antigen

Magnetic resonance (MR) imaging is advantageous because it concurrently provides anatomic, functional, and molecular information. MR molecular imaging can combine the high spatial resolution of this established clinical modality with molecular profiling in vivo. However, as a result of the intrinsically low sensitivity of MR imaging, high local concentrations of biological targets are required to generate discernable MR contrast. We hypothesize that the prostate‐specific membrane antigen (PSMA), an attractive target for imaging and therapy of prostate cancer, could serve as a suitable biomarker for MR‐based molecular imaging. We have synthesized three new high‐affinity, low‐molecular‐weight Gd^III‐based PSMA‐targeted contrast agents containing one to three Gd^III chelates per molecule. We evaluated the relaxometric properties of these agents in solution, in prostate cancer cells, and in an in vivo experimental model to demonstrate the feasibility of PSMA‐based MR molecular imaging.