High Relaxivity Values Research Articles

Employing antagonistic C-X-C motif chemokine receptor 4 antagonistic peptide functionalized NaGdF4 nanodots for magnetic resonance imaging-guided biotherapy of breast cancer

C-X-C motif chemokine receptor 4 (CXCR4) is a promising therapeutic target of breast cancer because it is overexpressed on cell surface of all molecular subtypes of breast cancer including triplenegative breast cancer (TNBC). Herein, CXCR4 antagonistic peptide-NaGdF4 nanodot conjugates (termed as anti-CXCR4-NaGdF4 NDs) have been constructed for magnetic resonance imaging (MRI)-guided biotherapy of TNBC through conjugation of the C-X-C Motif Chemokine 12 (CXCL12)-derived cyclic peptide with tryptone coated NaGdF4 nanodots (5 ± 0.5 nm in diameter, termed as Try-NaGdF4 NDs). The as-prepared anti-CXCR4-NaGdF4 NDs exhibits high longitudinal relaxivity (r1) value (21.87 mM−1S−1), reasonable biocompatibility and good tumor accumulation ability. The features of anti-CXCR4-NaGdF4 NDs improve the tumor-MRI sensitivity and facilitate tumor biotherapy after injection in mouse-bearing MDA-MB-231 tumor model in vivo. MRI-guided biotherapy using anti-CXCR4-NaGdF4 NDs enables to suppress 46% tumor growth. In addition, about 47% injection dose of anti-CXCR4-NaGdF4 NDs is found in the mouse urine at 24 h post-injection. These findings demonstrate that anti-CXCR4-NaGdF4 NDs enable to be used as renal clearable nanomedicine for biotherapy and MRI of breast cancer.

Folate Receptor Targeting Mn(II) Complex Encapsulated Porous Silica Nanoparticle as an MRI Contrast Agent for Early-State Detection of Cancer.

Cancer is recognized as one of the major causes of mortality, however, early-stage detection can increase the survival chance greatly. It is recognized that folate receptors are gradually overexpressed in the cellular membrane with the progress of cancer from stage 1 to stage 4. Utilizing the fact, herein, developed a porous silica nanoparticle system C1@SiO2-FA-NP; A) impregnated with thermodynamically stable Mn(II) complex (1) molecules within the core of the nanoparticle, and B) surface functionalized with folate units. It exhibited a high longitudinal relaxivity value r1 = 21.45 mM-1s-1 that substantially increased to r1 = 40.97 mM-1s-1 in the presence of 0.67mM concentration of BSA under the physiological condition. The in vitro fluorescent images after surface conjugation of C1@SiO2-FA-NP with FITC (fluorescein isothiocyanate) buttressed the inclusion of the nanoparticle exclusively within the cancerous HeLa cells than that of healthy HEK293 cells. The importance of the surface-bound folate unit in the nanoparticle is further established by comparing the fluorescent images of HeLa cells in the absence of the group. Finally, the applicability of C1@SiO2-FA-NP as the T1-weighted MRI contrast agent for early-stage cancer diagnosis is established within C57BL/6 mice after infecting the mice with HeLa cells.

Synthesis and characterization of cellulose nanocrystals/Gd2O3 nanocomposite as a dual-mode contrast agent for MRI via gamma-ray irradiation

This study developed a biocompatible nanocomposite using cellulose nanocrystals (CNCs), polyethylene glycol (PEG), and sodium hydroxide (NaOH), combined with gadolinium oxide nanoparticles (Gd2O3-NPs) through gamma radiation to decrease the size of nanoparticles and increase their uniformity. This research found that the (CNCs-PEG/NaOH)/Gd2O3 nanocomposite exhibits notable characteristics, including high saturation magnetization (1.44 emu/g), remarkable colloidal stability with a highly negative surface charge of −31.4 mV, and a small hydrodynamic size of 5.5 ± 0.7 nm. Furthermore, the MTT assay conducted on HeLa cell lines revealed the excellent biocompatibility of the (CNCs-PEG/NaOH)/Gd2O3 nanocomposite. No cytotoxic effects were observed, and the nanocomposite exhibited adequate cellular uptake. Moreover, the (CNCs-PEG/NaOH)/Gd2O3 nanocomposite displayed a remarkable enhancement effect on both T1 and T2-weighted images, with high r1 and r2 relaxivity values of 21.694 mM−1 s−1 and 43.799 mM−1 s−1, respectively, resulting in a relaxivity ratio (r2/r1) of 2.02 when compared to clinical and commercial agents. This biocompatible nanocomposite holds promise as a dual contrast agent in MRI and various other biomedical applications. It is envisaged that gamma irradiation is a good method to produce nanoparticles within the nanoscale range.

Gem-bisphosphonic acid-based double hydrophilic block copolymers: RAFT synthesis and comparative assembly with gadolinium ions for the formation of MRI contrast agents

The synthesis of double hydrophilic block copolymers (DHBCs) with one block containing bisphosphonic acid groups was performed by aqueous RAFT polymerization with two approaches, either starting from a PEO-based macro-chain transfer agent (macro-CTA) or by chain extension of a RAFT-capped bisphosphonic acrylate homopolymer with oligo(ethylene glycol) methyl ether acrylate (OEGA). By complexation with gadolinium and europium ions, these polymers are prone to form hybrid polyionic complexes (HPICs) as evidenced by mono- and multi-angle DLS, TEM and luminescence measurements. The obtained HPICs showed better chemical stability at low pH values compared to previously reported counterparts based on carboxylic and monophosphonic acid groups (i.e., PEO-b-PAA and PEO-b-PVPA respectively). Due to their high relaxivity values, the proposed HPICs show potential as contrast agents for magnetic resonance imaging (MRI).

The NMR relaxivity of gadolinium (III) solutions as the function of oxidation level and flake size of graphene oxide

Chelating by graphene oxide (GO) results in dramatic shortening of the proton relaxation times of Gd3+ aqueous solutions. However, the factors, leading to the increase of relaxivity values, and the mechanisms behind the observed phenomena remain elusive. In this work, we investigated how the relaxation times of the GO/Gd3+ solutions depend on the oxidation level and the flake size of GO. The values of spin-lattice (r1) and spin-spin (r2) relaxivities increase with the oxidation degree of the used GO samples. The relaxivity also increases with decreasing the particle size of GO flakes by sonication. The observed phenomena are explained by the increase in the number of the edge functional groups, generated under the influence of both parameters. The content of these groups, their formation, and chelation of Gd3+ ions is discussed in the manuscript. Viscosity of solutions does not directly affect the relaxation times. With the use of high oxidation level and small particle size GO samples we have registered the record high relaxivity values: r2 = 114.7 mM−1 s−1, and r1 = 97.0 mM−1 s−1. This opens straight routes for developing the GO/Gd3+ based MRI contrast agents.

Ultrasmall catechol-PEG-anchored ferrite nanoparticles for highly sensitive magnetic resonance angiography.

Highly sensitive iron oxide nanoparticles with stable, safe and efficient surface functionalization, as potential substitutes for gadolinium-based contrast agents (GBCAs) with increasing biosafety concerns, exhibit great potential for high-performance magnetic resonance angiography (MRA). Herein, we developed ultrasmall catechol-PEG-anchored ferrite nanoparticles (PEG-UMFNPs) for highly sensitive MRA. The obtained nanoprobe has a high T1 relaxivity value (7.2 mM-1 s-1) due to its ultrasmall size and Mn doping. It has a suitable hydrodynamic size of 20 nm, which prevents rapid vascular extravasation and renal clearance and prolongs its blood circulation time. In vivo MRA at 3.0 T using the nanoprobe shows that the arteries and veins of rats, even blood vessels as small as 0.32 mm, are distinctly visible, and the contrast enhancement can last for at least 1 h. In addition, due to the outstanding contrast enhancement and long circulation time, the stenosis and recanalization process of the rat's carotid artery can be continuously monitored with a single injection of the nanoprobe. Our study indicates that PEG-UMFNPs are outstanding MR imaging nanoprobes that can be used to diagnose vascular diseases without the biosafety issues of GBCAs.

H-ferritin-nanocaged gadolinium nanoparticles for ultra-sensitive MR molecular imaging.

Rationale: Magnetic resonance imaging (MRI) is a powerful diagnostic technology by providing high-resolution imaging. Although MRI is sufficiently valued in its resolving morphology, it has poor sensitivity for tracking biomarkers. Therefore, contrast agents are often used to improve MRI diagnostic sensitivity. However, the clinically used Gd chelates are limited in improving MRI sensitivity owing to their low relaxivity. The objective of this study is to develop a novel contrast agent to achieve a highly sensitive tracking of biomarkers in vivo. Methods: A Gd-based nanoprobe composed of a gadolinium nanoparticle encapsulated within a human H-ferritin nanocage (Gd-HFn) has been developed. The specificity and sensitivity of Gd-HFn were evaluated in vivo in tumor-bearing mice and apolipoprotein E-deficient mice (Apoe-/-) by MRI. Results: The Gd-HFn probe shows extremely high relaxivity values (r1 = 549 s-1mM-1, r2 = 1555 s-1mM-1 under a 1.5-T magnetic field; and r1 = 428 s-1mM-1 and r2 = 1286 s-1mM-1 under a 3.0-T magnetic field), which is 175-fold higher than that of the clinically standard Dotarem (Gd-DOTA, r1 =3.13 s-1mM-1) under a 1.5-T magnetic field, and 150-fold higher under a 3.0-T magnetic field. Owing to the substantially enhanced relaxivity values, Gd-HFn achieved a highly sensitive tracking for the tumor targeting receptor of TfR1 and enabled the in vivo MRI visualization of tumors approaching the angiogenic switch. Conclusions: The developed Gd-HFn contrast agent makes MRI a more powerful tool by simultaneously providing functional and morphological imaging information, which paves the way for a new perspective in molecular imaging.

Advances in MRI: Peptide and peptidomimetic-based contrast agents.

Magnetic resonance imaging (MRI) is a common medical imaging technique that provides three-dimensional body images. MRI contrast agents improve image contrast by raising the rate of water proton relaxation in specific tissues. Peptides and peptidomimetics act as scaffolds for MRI imaging agents because of their increased size and offer the possibility to engine a higher hydration value within the design. The design of a new Gd-based contrast agent must take into account high stability constants to avoid free Gd(III), with the subsequent nephrotoxicity, and high relaxivity values. This review analyzes various synthetic approaches, reports studies of relaxometric parameters, and focuses on the description and application of Gd(III)-chelates based on peptide and peptidomimetic scaffolds. In addition, the X-ray molecular structures of three DOTA complexes will be reported to emphasize the necessity of using the X-ray diffraction analysis to identify the coordination sphere of the metals and the mechanism of action of the compounds.

Review of the Efficacy and Safety of Gadopiclenol: A Newly Emerging Gadolinium-Based Contrast Agent.

Gadolinium-based contrast agents (GBCAs) are one of the most commonly used agents in magnetic resonance imaging. Gadopiclenol is a new GBCA aimed at providing improved diagnostic efficacy with a favorable safety profile. The proposed advantages are due to its specific pharmacological properties, one of which is high relaxivity values. The aim of this review is to assess the efficacy, diagnostic accuracy, and safety of gadopiclenol in comparison to other currently used gadolinium-based contrast agents. PubMed and other database systems were used to identify relevant studies. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed, resulting in 10 articles that were included in the review. The outcomes were reviewed according to several factors regarding efficacy and accuracy in terms of qualitative and quantitative descriptors relative to properties of enhancement provided by the contrast agent. In terms of safety profile, a number of outcomes were assessed such as the occurrence of serious adverse effects, severe kidney injury, and organ-based contrast retention. Gadopiclenol was found to provide outcomes comparable to other commonly used GBCAs at lower doses with further favorable results at higher doses while maintaining an acceptable safety profile. However, it was found to have high rates of retention within the liver and can cause nonsignificant QT prolongation in healthy individuals, which arguably creates the need for further research regarding more long-term implications of these possible adverse effects.

N-Acetylcysteine-Loaded Magnetic Nanoparticles for Magnetic Resonance Imaging.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by the rapid onset of lung inflammation Therefore, monitoring the spatial distribution of the drug directly administered to heterogeneously damaged lungs is desirable. In this work, we focus on optimizing the drug N-acetylcysteine (NAC) adsorption on poly-l-lysine-modified magnetic nanoparticles (PLLMNPs) to monitor the drug spatial distribution in the lungs using magnetic resonance imaging (MRI) techniques. The physicochemical characterizations of the samples were conducted in terms of morphology, particle size distributions, surface charge, and magnetic properties followed by the thermogravimetric quantification of NAC coating and cytotoxicity experiments. The sample with the theoretical NAC loading concentration of 0.25 mg/mL was selected as an optimum due to the hydrodynamic nanoparticle size of 154 nm, the surface charge of +32 mV, good stability, and no cytotoxicity. Finally, MRI relaxometry confirmed the suitability of the sample to study the spatial distribution of the drug in vivo using MRI protocols. We showed the prevailing transverse relaxation with high transverse relaxivity values and a high r2(*)/r1 ratio, causing visible hypointensity in the final MRI signal. Furthermore, NAC adsorption significantly affects the relaxation properties of PLLMNPs, which can help monitor drug release in vitro/in vivo.

Manganese-Doped Carbon Dots as a Promising Nanoprobe for Luminescent and Magnetic Resonance Imaging

Luminescent carbon nanodots (CDs) are a low-toxic nanomaterial with a tunable emission in a wide spectral range and with various functional groups on the surface. Therefore, CDs can prospectively serve as luminescent nanoprobes for biomedical applications, such as drug-delivery, visualization, sensing, etc. The doping of CDs with paramagnetic or transition metals allows the expansion of the range of applications of CDs and the fabrication of a multimodal nanoprobe for bioimaging. Here, we developed CDs doped with manganese (Mn) based on commonly used precursors—o-phenylenediamine or citric acid and formamide. The chemical structure, morphology, optical properties, and magnetic resonance responses have been carefully studied. The obtained CDs are up to 10 nm, with emissions observed in the 400–650 nm spectral region. CDs exhibit an ability to reduce both T1 and T2 relaxation times by up to 6.4% and 42.3%, respectively. The high relaxivity values suggest the use of CDs as promising dual-mode contrast agents for T1 and T2 MRI. Therefore, our developed CDs can be utilized as a new multifunctional nanoscale probe for photoluminescent and magnetic resonance bioimaging.

Углеродные наночастицы, легированные медью, как двух-модальный нанозонд для люминесцентной и магнитно-резонансной визуализации

In this work, copper-doped carbon nanoparticles with emission in a wide spectral range and the ability to change the relaxation times of water protons during magnetic resonance imaging were fabricated. A high relaxivity value r1 = 0.92 mM-1∙s-1 was achieved, which is the highest value of r1 for copper nanoparticles, to our knowledge. The suggested carbon nanoparticles are promising two-modal nanoprobes for bioimaging.

Gadolinium-doped fluorescent carbon quantum dots as MRI contrast agents and fluorescent probes

In this research passivated gadolinium-doped carbon quantum dots (Gd-doped CQDs) were synthesized from starch by a hydrothermal method. The X-ray diffraction (XRD) pattern of the Gd-doped CQDs showed the formation of highly amorphous carbon. The Fourier transform infrared spectroscopy (FTIR) results suggested that the CQDs are functionalized with C-N and N–H bonds. The synthesized CQDs with a size distribution of 2–8 nm have an absorption peak at 271 nm in UV–Visible spectroscopy (UV–Vis). The photoluminescence (PL) in CQDs was dependent on the excitation wavelength. The QY of the synthesized CQDs was calculated to be 13.2%. The Gd-doped CQDs exhibited sustained PL in ionic solutions with different ionic strengths and different temperatures up to 65 °C. Fluorescence imaging on mouse C34/connective tissue-L929 cells confirmed that Gd-doped CQDs could be well distributed over the cytoplasm. The magnetic resonance imaging (MRI) showed that the Gd-doped CQDs have extremely high longitudinal and transverse relaxivity values of as high as 218.28 mM−1 s−1 and 364.68 mM−1 s−1. The synthesized Gd-doped CQDs are promising candidates as multifunctional imaging probes and MRI contrast agents in biomedical diagnosis and brain mapping applications.

Target-switchable Gd(III)-DOTA/protein cage nanoparticle conjugates with multiple targeting affibody molecules as target selective T1 contrast agents for high-field MRI

Magnetic resonance imaging (MRI) is a non-invasive in vivo imaging tool, providing high enough spatial resolution to obtain both the anatomical and the physiological information of patients. However, MRI generally suffers from relatively low sensitivity often requiring the aid of contrast agents (CA) to enhance the contrast of vessels and/or the tissues of interest from the background. The targeted delivery of diagnostic probes to the specific lesion is a powerful approach for early diagnosis and signal enhancement leading to the effective treatment of various diseases. Here, we established targeting ligand switchable nanoplatforms using lumazine synthase protein cage nanoparticles derived from Aquifex aeolicus (AaLS) by genetically introducing the SpyTag peptide (ST) to the C-terminus of the AaLS subunits to form an ST-displaying AaLS (AaLS-ST). Conversely, multiple targeting ligands were constructed by genetically fusing SpyCatcher protein (SC) to either HER2 or EGFR targeting affibody molecules (SC-HER2Afb or SC-EGFRAfb). Gd(III)-DOTA complexes were chemically attached to the AaLS-ST and the external surface of the Gd(III)-DOTA conjugated AaLS-ST (Gd(III)-DOTA-AaLS-ST) were successfully decorated with either the HER2Afb or the EGFRAfb. The resulting Gd(III)-DOTA-AaLS/HER2Afb and Gd(III)-DOTA-AaLS/EGFR2Afb exhibited high r1 relaxivity values of 57 and 25 mM−1 s−1 at 1.4 and 7 T, respectively, which were 10-fold or higher than those of the clinically used Dotarem. Their target-selective contrast enhancements were confirmed with in vitro cell-based MRI scans and the in vivo MR imaging of tumor-bearing mouse models at 7 T. A target-switchable AaLS-based nanoplatform that was developed in this study might serve as a promising T1 CA developing platform at a high magnetic field to detect various tumor sites in a target-specific manner in future clinical applications.

A Gadolinium(III) Complex Based on the Thymine Nucleobase with Properties Suitable for Magnetic Resonance Imaging.

The paramagnetic gadolinium(III) ion is used as contrast agent in magnetic resonance (MR) imaging to improve the lesion detection and characterization. It generates a signal by changing the relaxivity of protons from associated water molecules and creates a clearer physical distinction between the molecule and the surrounding tissues. New gadolinium-based contrast agents displaying larger relaxivity values and specifically targeted might provide higher resolution and better functional images. We have synthesized the gadolinium(III) complex of formula [Gd(thy)2(H2O)6](ClO4)3·2H2O (1) [thy = 5-methyl-1H-pyrimidine-2,4-dione or thymine], which is the first reported compound based on gadolinium and thymine nucleobase. 1 has been characterized through UV-vis, IR, SEM-EDAX, and single-crystal X-ray diffraction techniques, and its magnetic and relaxometric properties have been investigated by means of SQUID magnetometer and MR imaging phantom studies, respectively. On the basis of its high relaxivity values, this gadolinium(III) complex can be considered a suitable candidate for contrast-enhanced magnetic resonance imaging.

In Vivo Positive Magnetic Resonance Imaging of Brain Cancer (U87MG) Using Folic Acid-Conjugated Polyacrylic Acid-Coated Ultrasmall Manganese Oxide Nanoparticles

Ultrasmall nanoparticles are potential candidates for application as high-performance imaging agents. Herein, we present the synthesis and characterization of folic acid (FA)-conjugated polyacrylic acid (PAA)-coated MnO nanoparticles with an average particle diameter of 2.7 nm. FA conferred cancer-targeting ability, while PAA conferred good colloidal stability and low cellular cytotoxicity on the FA-PAA-coated MnO nanoparticles. Further, the nanoparticles exhibited a high relaxivity (r1) value of 9.3 s−1mM−1 (r2/r1 = 2.2). Their application potential as cancer-targeting T1 magnetic resonance imaging contrast agents was confirmed by their enhanced T1 contrast enhancements at the brain cancer (U87MG) site upon intravenous administration to mice tails.

Folic acid-functionalized gadolinium-loaded phase transition nanodroplets for dual-modal ultrasound/magnetic resonance imaging of hepatocellular carcinoma

Dual-modal molecular imaging by combining two imaging techniques can provide complementary information for early cancer diagnosis and therapeutic monitoring. In the present manuscript, folic acid (FA)-functionalized gadolinium-loaded nanodroplets (NDs) are introduced as dual-modal ultrasound (US)/magnetic resonance (MR) imaging contrast agents. These phase-change contrast agents (PCCAs) with alginate (Alg) stabilizing shell and a liquid perfluorohexane (PFH) core were successfully synthesized via the nano-emulsion method and characterized. In this regard, mouse hepatocellular carcinoma (Hepa1-6) as target cancer cells and mouse fibroblast (L929) as control cells were used. The in vitro and in vivo cytotoxicity assessments indicated that Gd/PFH@Alg and Gd/PFH@Alg-FA nanodroplets are highly biocompatible. Gd-loaded NDs do not induce organ toxicity, and no significant hemolytic activity in human red blood cells is observed. Additionally, nanodroplets exhibited strong ultrasound signal intensities as well as T1-weighted MRI signal enhancement with a high relaxivity value of 6.40 mM−1 s−1, which is significantly higher than that of the clinical Gadovist contrast agent (r1 = 4.01 mM−1 s−1). Cellular uptake of Gd-NDs-FA by Hepa1-6 cancer cells was approximately 2.5-fold higher than that of Gd-NDs after 12 h incubation. Furthermore, in vivo results confirmed that the Gd-NDs-FA bound selectively to cancer cells and were accumulated in the tumor region. In conclusion, Gd/PFH@Alg-FA nanodroplets have great potential as US/MR dual-modal imaging nanoprobes for the early diagnosis of cancer.

Optimizing the relaxivity at high fields: systematic variation of the rotational dynamics in polynuclear Gd-complexes based on the AAZTA ligand

A homogeneous series of polynuclear Gd-complexes (n = 1–8) based on a stable and bis-hydrated [Gd(AAZTA)]− chelate shows high relaxivity values at high fields (1.5–7 T), per Gd, particularly pronounced for the more rigid and compact members.

MR Imaging of Peripheral Nerves Using Targeted Application of Contrast Agents: An Experimental Proof-of-Concept Study.

Introduction: Current imaging modalities for peripheral nerves display the nerve's structure but not its function. Based on a nerve's capacity for axonal transport, it may be visualized by targeted application of a contrast agent and assessing the distribution through radiological imaging, thus revealing a nerve's continuity. This concept has not been explored, however, may potentially guide the treatment of peripheral nerve injuries. In this experimental proof-of-concept study, we tested imaging through MRI after administering gadolinium-based contrast agents which were then retrogradely transported.Methods: We synthesized MRI contrast agents consisting of paramagnetic agents and various axonal transport facilitators (HSA-DTPA-Gd, chitosan-DTPA-Gd or PLA/HSA-DTPA-Gd). First, we measured their relaxivity values in vitro to assess their radiological suitability. Subsequently, the sciatic nerve of 24 rats was cut and labeled with one of the contrast agents to achieve retrograde distribution along the nerve. One week after surgery, the spinal cords and sciatic nerves were harvested to visualize the distribution of the respective contrast agent using 7T MRI. In vivo MRI measurements were performed using 9.4 T MRI on the 1st, 3rd, and the 7th day after surgery. Following radiological imaging, the concentration of gadolinium in the harvested samples was analyzed using inductively coupled mass spectrometry (ICP-MS).Results: All contrast agents demonstrated high relaxivity values, varying between 12.1 and 116.0 mM−1s−1. HSA-DTPA-Gd and PLA/HSA-DTPA-Gd application resulted in signal enhancement in the vertebral canal and in the sciatic nerve in ex vivo MRI. In vivo measurements revealed significant signal enhancement in the sciatic nerve on the 3rd and 7th day after HSA-DTPA-Gd and chitosan-DTPA-Gd (p < 0.05) application. Chemical evaluation showed high gadolinium concentration in the sciatic nerve for HSA-DTPA-Gd (5.218 ± 0.860 ng/mg) and chitosan-DTPA-Gd (4.291 ± 1.290 ng/mg).Discussion: In this study a novel imaging approach for the evaluation of a peripheral nerve's integrity was implemented. The findings provide radiological and chemical evidence of successful contrast agent uptake along the sciatic nerve and its distribution within the spinal canal in rats. This novel concept may assist in the diagnostic process of peripheral nerve injuries in the future.

Synthesis and In Vitro Studies of a Gd(DOTA)-Porphyrin Conjugate for Combined MRI and Photodynamic Treatment.

With the aim of developing new molecular theranostic agents, a π-extended Zn(II) porphyrin as photosensitizer for photodynamic therapy (PDT) linked to two GdDOTA-type complexes for magnetic resonance imaging (MRI) detection was synthesized. The relaxivity studies revealed a much higher relaxivity value per Gd ion for this medium sized molecule (19.32 mM-1 s-1 at 20 MHz and 298 K) compared to clinical contrast agents-a value which strongly increases in the presence of bovine serum albumin, reaching 25.22 mM-1 s-1. Moreover, the photophysical studies showed the strong ability of the molecule to absorb light in the deep red (670 nm, ε ≈ 60000 M-1 cm-1) and in the near-infrared following two-photon excitation (920 nm, σ2 ≈ 650 GM). The conjugate is also able to generate singlet oxygen, with a quantum yield of 0.58 in DMSO. Promising results were obtained in cellular studies, demonstrating that the conjugate is internalized in HeLa cells at micromolar concentration and leads to 70% of cell death following 30 min irradiation at 660 nm. These results confirm the potential of the designed molecule as an imaging and therapeutic agent.