Contrast Agents For Molecular Imaging Research Articles

A Polypeptide-Based, Membrane-Penetrating, Target-Specific Contrast Agent for Magnetic Resonance Molecular Imaging.

Molecular imaging based on magnetic resonance imaging (MRI) requires a contrast agent with high relaxivity and specificity. Much effort has been devoted to this goal over the past decades. In this work, we continue this endeavor by synthesizing an MRI contrast agent that can penetrate the cellular membrane and bind with specific proteins. It was characterized with one- and two-dimensional NMR spectroscopy, NMR micro-imaging, and mass spectroscopy. The target specificity has been further confirmed by both molecular dynamics simulation and micro-imaging on a living biological system. It is one of the largest of peptide-based bioactivated MRI contrast agents, and its relaxivity enhancement factor is among the highest of MRI contrast agents hitherto published. We envision interesting applications and extension of this smart MRI contrast agent with bio-specificity and high contrast for molecular imaging.

Fluorescent nanodiamond - hyaluronate conjugates for target-specific molecular imaging.

Despite wide investigation on molecular imaging contrast agents, there are still strong unmet medical needs to enhance their signal-to background ratio, brightness, photostability, and biocompatibility with multimodal imaging capability. Here, we assessed the feasibility of fluorescent nanodiamonds (FNDs) as carbon based photostable and biocompatible materials for molecular imaging applications. Because FNDs have negatively charged nitrogen vacancy (NV) centers, they can emit bright red light. FNDs were conjugated to hyaluronate (HA) for target-specific molecular imaging. HA is a biocompatible, biodegradable, and linear polysaccharide with abundant HA receptors in the liver, enabling liver targeted molecular imaging. In vitro cell viability tests revealed the biocompatibility of HA–FND conjugates and the competitive cellular uptake test confirmed their target-specific intracellular delivery to HepG2 cells with HA receptors. In addition, in vivo fluorescence lifetime (FLT) assessment revealed the imaging capability of FNDs and HA–FND conjugates. After that, we could confirm the statistically significant liver-targeted delivery of HA–FND conjugates by in vivo imaging system (IVIS) analysis and ex vivo biodistribution tests in various organs. The renal clearance test and histological analysis corroborated the in vivo biocompatibility and safety of HA–FND conjugates. All these results demonstrated the feasibility of HA–FND conjugates for further molecular imaging applications.

Vascular-targeted micelles as a specific MRI contrast agent for molecular imaging of fibrin clots and cancer cells

Molecular medical imaging is intended to increase the accuracy of diagnosis, particularly in cardiovascular and cancer-related diseases, where early detection could significantly increase the treatment success rate. In this study, we present mixed micelles formed from four building blocks as a magnetic resonance imaging targeted contrast agent for the detection of atheroma and cancer cells. The building blocks are a gadolinium-loaded DOTA ring responsible for contrast enhancement, a fibrin-specific CREKA pentapeptide responsible for targeting, a fluorescent dye and DSPE-PEG2000. The micelles were fully characterized in terms of their size, zeta potential, stability, relaxivity and toxicity. Target binding assays performed on fibrin clots were quantified by fluorescence and image signal intensities and proved the binding power. An additional internalization assay showed that the micelles were also designed to specifically enter into cancer cells. Overall, these multimodal mixed micelles represent a potential formulation for MRI molecular imaging of atheroma and cancer cells.

DNA-Based Nanocarriers to Enhance the Optoacoustic Contrast of Tumors In Vivo.

Optoacoustic tomography (OT) enables non-invasive deep tissue imaging of optical contrast at high spatio-temporal resolution. The applications of OT in cancer imaging often rely on the use of molecular imaging contrast agents based on near-infrared (NIR) dyes to enhance contrast at the tumor site. While these agents afford excellent biocompatibility and minimal toxicity, they present limited optoacoustic signal generation capability and rapid renal clearance, which can impede their tumor imaging efficacy. In this work, a synthetic strategy to overcome these limitations utilizing biodegradable DNA-based nanocarrier (DNA-NC) platforms is introduced. DNA-NCs enable the incorporation of NIR dyes (in this case, IRDye 800CW) at precise positions to enable fluorescence quenching and maximize optoacoustic signal generation. Furthermore, these DNA-NCs show a prolonged blood circulation compared to the native fluorophores, facilitating tumor accumulation by the enhanced permeability and retention (EPR) effect. In vivo imaging of tumor xenografts in mice following intravenous administration of DNA-NCs reveals enhanced OT signals at 24 h when compared to free fluorophores, indicating promise for this method to enhance the optoacoustic signal generation capability and tumor uptake of clinically relevant NIR dyes.

TAILORING THE NANOPARTICLES SURFACE FOR EFFICIENT CANCER THERAPEUTICS DELIVERY

Nanotechnology has tremendous advantages in many areas of scientific as well as clinical research. The development of nanoparticles (NPs) that can efficiently deliver drugs specifically to the cancer cells can help reduce normal cells toxicity and co-morbidities. Cancer can be treated by exploiting the unique physiochemical of the NPs, and modulating their surface modifications using ligands which further could be used as drug cargo vehicles. To enhance biocompatibility and drug delivery towards the target site, various modifications can be included to modify the surface of the NPs, such as carbohydrates, dendrimers, DNA, RNA, siRNA, drugs, and other ligands. These ligand-coated NPs have potential applications in the field of biomedical research, including diagnosis, contrast agents for molecular and clinical imaging (Magnetic Resonance Imaging (MRI), Computed tomography (CT), positron emission tomography (PET)), as cargo vehicles for drugs, increasing the blood circulation half-life, and blood detoxification. Further, the conjugation of anti-cancer drugs to the NPs can be efficiently used to target the cancer disease. This review highlights some of the features and surface modification strategies of the NPs, such as an iron oxide (IO), liposomes (LP)-based NPs, and polymer-based NPs, which show their effectiveness as cargo agents for cancer therapeutics.

Collagenase-Cleavable Peptide Amphiphile Micelles as a Novel Theranostic Strategy in Atherosclerosis.

Atherosclerosis is an inflammatory disease characterized by plaques that can cause sudden myocardial infarction upon rupture. Such rupture-prone plaques have thin fibrous caps due to collagenase degradation, and a noninvasive diagnostic tool and targeted therapy that can identify and treat vulnerable plaques and may inhibit the onset of acute cardiac events. Toward this goal, monocyte-binding, collagenase-inhibiting, and gadolinium-modified peptide amphiphile micelles (MCG PAMs) are developed. Monocyte chemoattractant protein-1 (MCP-1) binds to C-C chemokine receptor-2 expressed on pathological cell types present within plaques. Through the peptide binding motif of MCP-1, MCG PAMs bind to monocytes and vascular smooth muscle cells in vitro. Moreover, using magnetic resonance imaging, MCG PAMs show enhanced targeting and successful detection of plaques in diseased mice in vivo and act as contrast agents for molecular imaging. Through the collagenase-cleaving peptide sequence of collagen [VPMS-MRGG], MCG PAMs can compete for collagenases that degrade the fibrous cap of plaques, providing therapy. MCG PAM-treated mice show increased fibrous cap thickness by 61% and 113% histologically compared to nontargeting micelle- or PBS-treated mice (p = 0.0075 and 0.001, respectively). Overall, this novel multimodal nanoparticle offers new theranostic opportunities for noninvasive diagnosis and treatment of atherosclerotic plaques.

Surface-modified GVs as nanosized contrast agents for molecular ultrasound imaging of tumor

Nanobubbles, as a kind of new ultrasound contrast agent (UCAs), have shown promise to penetrate tumor vasculature to allow for targeted imaging. However, their inherent physical instability is an ongoing concern that could weaken their imaging ability with ultrasound. Gas vesicles (GVs), which are genetically encoded, naturally stable nanostructures, have been developed as the first ultrasonic biomolecular reporters which showed strong contrast enhancement. However, further development of tumor imaging with GVs is limited by the quick clearance of GVs by the reticuloendothelial system (RES). Here, we developed PEGylated HA-GVs (PH-GVs) for in-tumor molecular ultrasound imaging by integrating polyethylene glycol (PEG) and hyaluronic acid (HA) in GV shells. PH-GVs were observed to accumulate around CD44-positive cells (SCC7) but not be internalized by macrophage cell line RAW 264.7. Green fluorescence from PH-GVs was found around cell nuclei in the tumor site after 6 h and the signal was sustained over 48 h following tail injection, demonstrating PH-GVs’ ability to escape the clearance from the RES and to penetrate tumor vasculature through enhanced permeability and retention (EPR) effects. Further, PH-GVs produced strong ultrasound contrast in the tumor site in vivo, with no obvious side-effects detected following intravenous injection. Thus, we demonstrate the potential of PH-GVs as novel, nanosized and targeted UCAs for efficient and specific molecular tumor imaging, paving the way for the application of GVs in precise and personalized medicine.

In Vivo Immunofluorescence Localization for Assessment of Therapeutic and Diagnostic Antibody Biodistribution in Cancer Research.

Monoclonal antibodies (mAbs) are important tools in cancer detection, diagnosis, and treatment. They are used to unravel the role of proteins in tumorigenesis, can be directed to cancer biomarkers enabling tumor detection and characterization, and can be used for cancer therapy as mAbs or antibody-drug conjugates to activate immune effector cells, to inhibit signaling pathways, or directly kill cells carrying the specific antigen. Despite clinical advancements in the development and production of novel and highly specific mAbs, diagnostic and therapeutic applications can be impaired by the complexity and heterogeneity of the tumor microenvironment. Thus, for the development of efficient antibody-based therapies and diagnostics, it is crucial to assess the biodistribution and interaction of the antibody-based conjugate with the living tumor microenvironment. Here, we describe In Vivo Immunofluorescence Localization (IVIL) as a new approach to study interactions of antibody-based therapeutics and diagnostics in the in vivo physiological and pathological conditions. In this technique, a therapeutic or diagnostic antigen-specific antibody is intravenously injected invivo and localized ex vivo with a secondary antibody in isolated tumors. IVIL, therefore, reflects the in vivo biodistribution of antibody-based drugs and targeting agents. Two IVIL applications are described assessing the biodistribution and accessibility of antibody-based contrast agents for molecular imaging of breast cancer. This protocol will allow future users to adapt the IVIL method for their own antibody-based research applications.

Latest developments in molecular tracers for fluorescence image-guided cancer surgery.

Real-time intraoperative guidance is essential during oncological surgery for complete and safe tumour resection. Fluorescence imaging in the near-infrared spectrum has shown potential for guiding surgeons during complex interventions. Recently, there has been a shift towards the use of fluorescence contrast agents for molecular imaging. The first targeted fluorescent agents, of which most consist of approved therapeutic antibodies conjugated to a fluorescent dye, have been evaluated in several early-phase clinical trials. Moreover, advances in protein engineering and drug design have led to the development of a variety of tracers suitable for molecular fluorescence image-guided surgery. In this Review, we discuss preclinical and clinical evidence, ongoing clinical trials, and the latest developments in the field of molecular near-infrared tracers for fluorescence-guided cancer surgery.

Affibody-Indocyanine Green Based Contrast Agent for Photoacoustic and Fluorescence Molecular Imaging of B7-H3 Expression in Breast Cancer.

Spectroscopic photoacoustic (sPA) molecular imaging has high potential for identification of exogenous contrast agents targeted to specific markers. Antibody-dye conjugates have recently been used extensively for preclinical sPA and other optical imaging modalities for highly specific molecular imaging of breast cancer. However, antibody-based agents suffer from long circulation times that limit image specificity. Here, the efficacy of a small protein scaffold, the affibody (ABY), conjugated to indocyanine green (ICG), a near-infrared fluorescence dye, as a targeted molecular imaging probe is demonstrated. In particular, B7-H3 (CD276), a cellular receptor expressed in breast cancer, was imaged via sPA and fluorescence molecular imaging to differentiate invasive tumors from normal glands in mice. Administration of ICG conjugated to an ABY specific to B7-H3 (ABYB7-H3-ICG) showed significantly higher signal in mammary tumors compared to normal glands of mice. ABYB7-H3-ICG is a compelling scaffold for molecular sPA imaging for breast cancer detection.

Near-Infrared Fluorescent Rosol Dye Tailored toward Lymphatic Mapping Applications.

An optical molecular imaging contrast agent that is tailored toward lymphatic mapping techniques implementing near-infrared (NIR) fluorescence image-guided navigation in the planning and surgical treatment of cancers would significantly aid in enabling the real-time visualization of the potential metastatic tumor-draining lymph node(s) for theirneeded surgical biopsy and/or removal, thereby ensuring unmissed disease to prevent recurrence and improve patientsurvival rates. Here, the development of the first NIR fluorescent rosol dye (THQ-Rosol) tailored to overcome thelimitations arising from the suboptimal properties of the generic molecular fluorescent dyes commonly used for such applications is described. In developing THQ-Rosol, we prepared a progressive series of torsionally restrictive N-substituted non-NIR fluorescentrosol dyes based on density functional theory (DFT) calculations, wherein we discerned high correlations amongst their calculated energetics, modeled N-C3' torsion angles, and evaluated properties. We leveraged these strong relationships to rationally design THQ-Rosol, wherein DFT calculations inspired an innovative approach and synthetic strategy to afford an uncharged xanthene core-based scaffold/molecular platform with an aptly elevated p Ka value alongside NIR fluorescence emission (ca.700-900 nm). THQ-Rosol exhibited 710 nm NIR fluorescence emission, a 160 nm Stokes shift, robust photostability, and an aptly elevated p Ka value (5.85) for affording pH-insensitivity and optimal contrast upon designed use. We demonstrated the efficacy of THQ-Rosol for lymphatic mapping with in vitro and in vivo studies, wherein it revealed timely tumor drainage and afforded definitive lymph node visualization upon itsadministration and accumulation. THQ-Rosol serves as a proof-of-concept for the effective tailoring of an uncharged xanthene core-based scaffold/molecular platform toward a specific imaging application using rational design.

Designing Calcium-Binding Proteins for Molecular MR Imaging.

Early diagnosis, noninvasive detection, and staging of various diseases, remain one of the major clinical barriers to effective medical treatment and prevention of disease progression toward major clinical consequences. Molecular imaging technologies play an indispensable role in the clinical field in overcoming these major barriers. The increasing application of imaging techniques and agents in early detection of different diseases such as cancer has resulted in improved treatment response and clinical patient management. In this chapter we will first introduce criteria for the design and engineering of calcium-binding protein (CaBP) parvalbumin as a protein Gd-MRI contrast agent (ProCA) with unprecedented metal selectivity for Gd3+ over physiological metal ions. We will then discuss the further development of targeted MRI contrast agent for molecular imaging of PSMA biomarker for early detection of prostate cancer.

Ultrasound-Targeted Delivery Technology: A Novel Strategy for Tumor- Targeted Therapy.

Ultrasound has been widely used in clinical diagnosis because it is noninvasive, inexpensive, simple, and reproducible. With the development of molecular imaging, material science, and ultrasound contrast agents, ultrasound-targeted delivery technology has emerged. The interaction of ultrasound and molecular probes can be exploited to change the structures of cells and tissues in order to promote the targeted release of therapeutic substances to local tumors. The targeted delivery of drugs, genes, and gases would not only improve the efficacy of tumor treatment but also avoid the systemic toxicity and side effects caused by antitumor treatments. This technology was recently applied in clinical trials and showed enormous potential for clinical application. This article briefly introduces the characteristics of the tumor microenvironment and the principle of ultrasound-targeted delivery technology. To present recent progress in this field, this review focuses on the application of ultrasound-targeted delivery technology in tumor-targeted therapy, including drug delivery, gene transfection, and gas treatment. The results of this study show that ultrasound-targeted delivery technology is a promising therapeutic strategy for tumor treatment. Ultrasound-targeted delivery technology shows promise with regard to cancer treatment.

Preparation of Cationic Lipid-coated Ultrasound Contrast Agents and Noninvasive Gene Transfection Via Ultrasound-targeted Microbubble Destruction.

Ultrasound contrast agents involving a therapeutic drug applied during enhanced imaging can be used for targeted therapy. The preparation of contrast agents is a precondition and basis for the use of multifunctional contrast agents in molecular imaging. This study uses thin-film hydration-mechanical vibration to carry out the preliminary preparation of a cationic contrast agent (CCA); characterizes the particle diameter, potential, distribution, and concentration of the agents; and optimizes the factors affecting the preparation of the agents. This study found that thin-film hydration-mechanical vibration methods offer a better preparation effectiveness and achieve smaller particle diameters and more even distributions, as well as give better imaging performance. Different concentrations of CCA and plasmid and different gene transfection methods can produce different degrees of sonoporation to achieve optimal transfection efficiency. Ultrasound parameters have a great influence on transfection efficiency and plasmid integrity. A previous study confirmed that the ultrasound parameters of 1 MHz, 1 W/cm2, a duty cycle controller (DC) of 20%, and irradiation for 1 min can well deliver genes to tumor cells, with little impact on cell survival. Our findings indicate that ultrasound-targeted microbubble destruction (UTMD)-mediated CCA destruction facilitates gene transfection and may represent an effective gene delivery method for cervical cancer therapy.

Effects of Deuteration of 13C-Enriched Phospholactate on Efficiency of Parahydrogen-Induced Polarization by Magnetic Field Cycling.

We report herein a large-scale (>10 g) synthesis of isotopically enriched 1-13C-phosphoenolpyruvate and 1-13C-phosphoenolpyruvate-d2 for application in hyperpolarized imaging technology. The 1-13C-phosphoenolpyruvate-d2 was synthesized with 57% overall yield (over two steps), and >98% 2H isotopic purity, representing an improvement over the previous report. The same outcome was achieved for 1-13C-phosphoenolpyruvate. These two unsaturated compounds with C=C bonds were employed for parahydrogen-induced polarization via pairwise parahydrogen addition in aqueous medium. We find that deuteration of 1-13C-phosphoenolpyruvate resulted in overall increase of 1H T1 of nascent hyperpolarized protons (4.30 ± 0.04 s versus 2.06 ± 0.01 s) and 1H polarization (~2.5% versus ~0.7%) of the resulting hyperpolarized 1-13C-phospholactate. The nuclear spin polarization of nascent parahydrogen-derived protons was transferred to 1-13C nucleus via magnetic field cycling procedure. The proton T1 increase in hyperpolarized deuterated 1-13C-phospholactate yielded approximately 30% better 13C polarization compared to non-deuterated hyperpolarized 1-13C-phospholactate. Analysis of T1 relaxation revealed that deuteration of 1-13C-phospholactate may have resulted in approximately 3-fold worse H→13C polarization transfer efficiency via magnetic field cycling. Since magnetic field cycling is a key polarization transfer step in the Side-Arm Hydrogenation approach, the presented findings may guide more rationale design of contrast agents using parahydrogen polarization of a broad range of 13C hyperpolarized contrast agents for molecular imaging employing 13C MRI. The hyperpolarized 1-13C-phospholactate-d2 is of biomedical imaging relevance because it undergoes in vivo dephosphorylation and becomes 13C hyperpolarized lactate, which as we show can be detected in the brain using 13C hyperpolarized MRI; an implication for future imaging of neurodegenerative diseases and dementia.

Synthesis of Unsaturated Precursors for Parahydrogen-Induced Polarization and Molecular Imaging of 1-13C-Acetates and 1-13C-Pyruvates via Side Arm Hydrogenation.

Hyperpolarized forms of 1-13C-acetates and 1-13C-pyruvates are used as diagnostic contrast agents for molecular imaging of many diseases and disorders. Here, we report the synthetic preparation of 1-13C isotopically enriched and pure from solvent acetates and pyruvates derivatized with unsaturated ester moiety. The reported unsaturated precursors can be employed for NMR hyperpolarization of 1-13C-acetates and 1-13C-pyruvates via parahydrogen-induced polarization (PHIP). In this PHIP variant, Side arm hydrogenation (SAH) of unsaturated ester moiety is followed by the polarization transfer from nascent parahydrogen protons to 13C nucleus via magnetic field cycling procedure to achieve hyperpolarization of 13C nuclear spins. This work reports the synthesis of PHIP-SAH precursors: vinyl 1-13C-acetate (55% yield), allyl 1-13C-acetate (70% yield), propargyl 1-13C-acetate (45% yield), allyl 1-13C-pyruvate (60% yield), and propargyl 1-13C-pyruvate (35% yield). Feasibility of PHIP-SAH 13C hyperpolarization was verified by 13C NMR spectroscopy: hyperpolarized allyl 1-13C-pyruvate was produced from propargyl 1-13C-pyruvate with 13C polarization of ∼3.2% in CD3OD and ∼0.7% in D2O. 13C magnetic resonance imaging is demonstrated with hyperpolarized 1-13C-pyruvate in aqueous medium.

CT imaging of myocardial scar burden with CNA35-conjugated gold nanoparticles

Management of patients suffering from myocardial infarction (MI) is based on the extent of coronary artery disease and myocardial scar burden. We have developed a potentially clinically-useful X-ray molecular imaging contrast agent based on gold nanoparticle (AuNPs) functionalized with collagen-binding adhesion protein 35 (CNA35) with the capabilities of achieving prolonged blood pool enhancement for vascular imaging of the coronary arteries and specific targeting of collagen within myocardial scar. At a concentration of ~ 45 mg Au/ml, AuNPs maintained a stable blood pool enhancement at 142–160 HU within an hour of intravenous administration. At 6 hours, specific signal enhancement was detected in the myocardium scar in rats injected with CNA35-AuNPs, but not with control AuNPs or in control animals. In conclusion, CNA35-AuNPs may be considered as a CT contrast agent for both vascular imaging of coronary artery disease and molecular imaging of myocardial scar in the heart.

Porphyrin-Implanted Carbon Nanodots for Photoacoustic Imaging and in Vivo Breast Cancer Ablation

The incorporation of intensive light absorbing porphyrins macrocycles with biocompatible nanoparticles would lead to new nanomaterials with multiple imaging and therapeutic modalities. Herein, a facile synthetic strategy has been applied to prepare porphyrin-implanted carbon nanodots (PNDs) by partial and selective pyrolysis of 5,10,15,20-tetrakis(4-aminophenyl)porphyrin (TAPP) and citric acid (CA) at an appropriate temperature. As-prepared PNDs exhibit not only the excellent stability and biocompatibility characteristic of carbon nanodots but also the unique properties of porphyrin macrocycle such as strong UV–visible and near-infrared absorption, specifically, high photodynamic therapy efficiency. More importantly, the PNDs with near-infrared absorption could act as a contrast agent for photoacoustic molecular imaging with deep tissue penetration and fine spatial resolution. The Cetuximab-conjugated porphyrin-based carbon nanodots (C225-PNDs) have been further prepared to precisely target the cancer cel...

Salicylic Acid-Based Polymeric Contrast Agents for Molecular Magnetic Resonance Imaging of Prostate Cancer.

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is an innovative molecular imaging technique in which contrast agents are labeled by saturating their exchangeable proton spins by radio-frequency irradiation. Salicylic acid and its analogues are a promising class of highly sensitive, diamagnetic CEST agents. Herein, polymeric agents grafted with salicylic acid moieties and a known high-affinity ligand targeting prostate-specific membrane antigen in approximately 10:1 molar ratio were synthesized to provide sufficient MRI sensitivity and receptor specificity. The proton-exchange properties of the contrast agent in solution and in an experimental murine model are reported to demonstrate the feasibility of receptor-targeted CEST MRI of prostate cancer. Furthermore, the CEST imaging data were validated with an 111 In-labeled analogue of the agent by in vivo single photon emission computed tomographic imaging and tissue biodistribution studies.

Novel bionanotechnological solutions based on metal oxide and metal to preserve and assess organs for transplantation

Our research has focused on nanomaterials for the diagnosis and treatment of cardiovascular disease (CVD) such as thrombosis. These materials can be adapted for preserving and assessing organs for transplantation. Magnetic resonance imaging (MRI) has been used as a powerful and indispensable tool in medical research and clinical diagnosis. We have developed both targeted negative contrast agents and targeted dual positive/negative contrast agents for molecular imaging of thrombosis. The simultaneous use of positive and negative MRI imaging that employs the same contrast agents will significantly improve detection accuracy. Using the dual contrast agent, both T1- and T2-weighted MRI of thrombosis can be simultaneously recorded which enables self-confirmation of images and leads to a greater diagnostic accuracy1 . To prepare these targeted agents, we employed a single-chain antibody that targets activated platelets, a major player in thrombus formation. Our contrast agents can be adapted for assessing organs during and after transplantation. It has been reported that platelets are activated early during reperfusion after an ischaemia/reperfusion injury (IRI). Therefore, by targeting activated platelets and platelet accumulation, it is possible to noninvasively detect and assess IRI early, maximizing medical interventions. We have also developed smart MRI nanosensors based on iron oxide and gadolinium that can not only detect, but also sense and report the stage or progression of CVD such as thrombosis. The early detection and accurate characterization of life-threatening diseases such as CVD are critical to the design of treatment. Knowing whether a thrombus in a blood vessel is new/fresh or old/constituted is very important for physicians to decide on a treatment protocol. These nanosensors can be adapted, modified and applied for detecting and grading other diseases such as cancer, and also for sensitive detection of inflammatory reactions during organ preservation, perfusion and transplantation processes. It can be a useful technique to potentially allow other researchers to access information previously difficult to obtain. It can also be a new tool for clinicians to assess organs before and after transplantation, maximizing opportunities for medical intervention. Since our nanosensors are iron oxide and gadolinium based materials, they can also be used for preservation of organs/tissues. Recently researchers have reported a way to safely thaw frozen tissues with the aid of iron oxide nanoparticles2 . By suffusing the nanosensors over organs/tissues before freezing, they may help in the thawing process and may directly provide information on inflammatory reactions within the organs/tissues after thawing and reperfusion