WazaGaY: An Innovative Aza-BODIPY-Derived Near-Infrared Fluorescent Probe for Enhanced Tumor Imaging.

Aza-BODIPYs represent a class of fluorophores in which the π-conjugated system is rigidified and stabilized by a boron atom. A promising strategy to enhance their fluorescence properties involves replacing the boron atom with a metal ion. Here, we describe the synthesis and characterization of a water-soluble derivative where the metal is a gallium(III) ion, termed WazaGaY (water-soluble aza-GaDIPY).

Comparison of the In Vitro and In Vivo Behavior of a Series of NIR-II-Emitting Aza-BODIPYs Containing Different Water-Solubilizing Groups and Their Trastuzumab Antibody Conjugates.

The development of new fluorescent organic probes effective in the NIR-II region is currently a fast-growing field and represents a challenge in the domain of medical imaging. In this study, we have designed and synthesized an innovative series of aza-boron dipyrromethenes emitting in the NIR-II region. We have investigated the effect of different water-solubilizing groups not only on the photophysical properties of the compounds but also on their in vitro and in vivo performance after bioconjugation to the antibody trastuzumab.

Development of an Immuno-SPECT/Fluorescent Bimodal Tracer Targeting Human or Murine PD-L1 on Preclinical Models.

Detection of biomarkers to diagnose, treat, and predict the efficacy of cancer therapies is a major clinical challenge. Currently, biomarkers such as PD-L1 are commonly detected from biopsies, but this approach does not take into account the spatiotemporal heterogeneity of their expression in tumors. A solution consists in conjugating monoclonal antibodies (mAbs) targeting these biomarkers with multimodal imaging probes.

In vivo validation of Ga-labeled AMD3100 conjugates for PET imaging of CXCR4.

Introduction: The chemokine receptor CXCR4 has been shown to be over-expressed in multiple types of cancer and is usually associated with aggressive phenotypes and poor prognosis. Successfully targeting and imaging the expression level of this receptor in tumours could inform treatment selection and facilitate patient stratification.

Methods: Known conjugates of AMD3100 that are specific to CXCR4 have been radiolabelled with gallium-68 and evaluated in naïve and tumour-bearing mice.

First Comparison Study of the and Properties of a Randomly and Site-Specifically Conjugated SPECT/NIRF Monomolecular Multimodal Imaging Probe (MOMIP) Based on an aza-BODIPY Fluorophore.

Among all approaches in molecular imaging, the combination of near-infrared fluorescence imaging (NIRF) with radioisotopic imaging (PET or SPECT) allows one to benefit from the advantages of each of the imaging techniques, which are very complementary and of comparable sensitivity. To this end, the construction of monomolecular multimodal probes (MOMIP) has made it possible to combine the two imaging modalities within the same molecule, thus limiting the number of bioconjugation sites and yielding more homogeneous conjugates compared with those prepared through sequential conjugation. However, in order to optimize the bioconjugation strategy and, at the same time, the pharmacokinetic and biodistribution properties of the resulting imaging agent, a site-specific approach may be preferred.

Al(III) and Ga(III) Bisphenolate Azadipyrromethene-Based "NO" Complexes as Efficient NIR-Fluorophores.

Aza-boron-dipyrromethenes (Aza-BODIPYs) are an increasingly studied class of fluorophores. They can be seen as an azadipyrromethene ("aza-DIPY") ligand rigidified by a metalloid, a boron atom. Based on this idea, a series of complexes of group 13 metals (aluminum and gallium) have been synthesized and characterized.

Tailored hyaluronic acid-based nanogels as theranostic boron delivery systems for boron neutron cancer therapy.

Boron-rich nanocarriers possess great potential for advanced boron neutron capture therapy (BNCT) as an effective radiation treatment for invasive malignant tumors. If additionally, they can be imaged in a non-invasive and real-time manner allowing the assessment of local boron concentration, they could serve for dose calculation and image-guided BNCT to enhance tumor treatment efficacy. To meet this challenge, this study describes the design of a theranostic nanogel, enriched in B and fluorescent dye, to achieve selective imaging, and sufficient accumulation of boron at the tumor site.

Lipoprotein interactions with water-soluble NIR-II emitting aza-BODIPYs boost the fluorescence signal and favor selective tumor targeting.

Following intravenous administration, the interaction of fluorescent exogenous molecules with circulating endogenous transporters can influence their photophysical properties as well as their fate and distribution, and possibly their recognition by different cell types. This type of interaction can be used to optimize the drug delivery but also the imaging properties of a compound of interest. In this study, we investigated the behavior of SWIR-WAZABY-01 fluorophore, a water-soluble aza-BODIPY dye emitting in the NIR-II region, both and .

Conception and Evaluation of Fluorescent Phosphine-Gold Complexes: From Synthesis to in vivo Investigations.

A phosphine gold(I) and phosphine-phosphonium gold(I) complexes bearing a fluorescent coumarin moiety were synthesized and characterized. Both complexes displayed interesting photophysical properties: good molar absorption coefficient, good quantum yield of fluorescence, and ability to be tracked in vitro thanks to two-photon imaging. Their in vitro and in vivo biological properties were evaluated onto cancer cell lines both human and murine and into CT26 tumor-bearing BALB/c mice.

Development of an Easily Bioconjugatable Water-Soluble Single-Photon Emission-Computed Tomography/Optical Imaging Bimodal Imaging Probe Based on the aza-BODIPY Fluorophore.

A water-soluble fluorescent aza-BODIPY platform (Wazaby) was prepared and functionalized by a polyazamacrocycle agent and a bioconjugable arm. The resulting fluorescent derivative was characterized and bioconjugated onto a trastuzumab monoclonal antibody as a vector. After bioconjugation, the imaging agent appeared to be stable in serum (>72 h at 37 °C) and specifically labeled HER-2-positive breast tumors slices.

Near-infrared emitting fluorescent homobimetallic gold(I) complexes displaying promising in vitro and in vivo therapeutic properties.

Three near-infrared (NIR-I) optical theranostic systems were synthesized, characterized and studied in vitro and in vivo. These original homo-bimetallic gold(I)-based aza-BODIPY complexes proved to be trackable through near-infrared optical imaging in cells and in mice. They display anti-proliferative properties in micromolar range against human and murine cancer cell lines (4T1, MDA-MB-231, CT26, and SW480).

Aza-BODIPY: A New Vector for Enhanced Theranostic Boron Neutron Capture Therapy Applications.

Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on the nuclear capture of slow neutrons by stable B atoms followed by charged particle emission that inducing extensive damage on a very localized level (<10 μm). To be efficient, a sufficient amount of B should accumulate in the tumor area while being almost cleared from the normal surroundings. A water-soluble aza-boron-dipyrromethene dyes (BODIPY) fluorophore was reported to strongly accumulate in the tumor area with high and BNCT compatible Tumor/Healthy Tissue ratios.

Water-Soluble Aza-BODIPYs: Biocompatible Organic Dyes for High Contrast NIR-II Imaging.

A simple NIR-II emitting water-soluble system has been developed and applied and . , the fluorophore quickly accumulated in 2D and 3D cell cultures and rapidly reached the tumor in rodents, showing high NIR-II contrast for up to 1 week. This very efficient probe possesses all the qualities necessary for translation to the clinic as well as for the development of NIR-II emitting materials.

Aza-BODIPY Platform: Toward an Efficient Water-Soluble Bimodal Imaging Probe for MRI and Near-Infrared Fluorescence.

In this study, an original aza-BODIPY system comprising two Gd complexes has been designed and synthesized for magnetic resonance imaging/optical imaging applications, by functionalization of the boron center. This strategy enabled the obtainment of a positively charged bimodal probe, which displays an increased water solubility, optimized photophysical properties in the near-infrared region, and very promising relaxometric properties. The absorption and emission wavelengths are 705 and 741 nm, respectively, with a quantum yield of around 10% in aqueous media.

Innovative Magnetic Nanoparticles for PET/MRI Bimodal Imaging.

Superparamagnetic iron oxide nanoparticles were developed as positron emission tomography (PET) and magnetic resonance imaging (MRI) bimodal imaging agents. These nanoparticles (NPs), with a specific nanoflower morphology, were first synthesized and simultaneously functionalized with 3,4-dihydroxy-l-phenylalanine (LDOPA) under continuous hydrothermal conditions. The resulting NPs exhibited a low hydrodynamic size of 90 ± 2 nm.

Rapid Synthesis and Antiproliferative Properties of Polyazamacrocycle-Based Bi- and Tetra-Gold(I) Phosphine Dithiocarbamate Complexes.

A family of bi- and tetrametallic gold(I) phosphine dithiocarbamate complexes were synthesized, starting from cyclam and dimethylcyclam polyazamacrocycles, respectively, along with their monometallic gold(I) chloridophosphine precursors. Their antiproliferative properties were evaluated on two cancer cell lines (A549 and NSCLC-N6-L16). Most of the mono- and bimetallic complexes displayed strong activities and, in particular, one bimetallic derivative showed antiproliferative properties in the low micromolar range.

A Promising Family of Fluorescent Water-Soluble aza-BODIPY Dyes for in Vivo Molecular Imaging.

A new family of water-soluble and bioconjugatable aza-BODIPY fluorophores was designed and synthesized using a boron- functionalization strategy. These dissymmetric bis-ammonium aza-BODIPY dyes present optimal properties for a fluorescent probe; i.e.

Copper radiopharmaceuticals for theranostic applications.

The growing advancement in nuclear medicine challenges researchers from several different fields to integrate imaging and therapeutic modalities in a theranostic radiopharmaceutical, which can be defined as a molecular entity with readily replaceable radioisotope to provide easy switch between diagnostic and therapeutic applications for efficient and patient-friendly treatment of diseases. For such a reason, the diagnostic and therapeutic potential of all five medical radionuclides of copper have thoroughly been investigated as they boost the hope for development of successful radiotheranostics. To facilitate the mutual understanding between all different specialists working on this multidisciplinary field, we summarized the recent updates in copper-based nuclear medicine, with specific attention to the potential theranostic applications.

Design of a multifunctionalizable BODIPY platform for the facile elaboration of a large series of gold(i)-based optical theranostics.

A simple trifunctional BODIPY platform was designed. The high potential of this platform was validated via the elaboration of twelve optical theranostics. More specifically, we reported on the synthesis, the characterization, the photophysical properties, and the evaluation of the hydrophilicity properties of the different BODIPY derivatives, as well as a theoretical rationalization of the intriguing chemical behavior of some of them.

Cellular imaging using BODIPY-, pyrene- and phthalocyanine-based conjugates.

Fluorescent Probes aimed at absorbing in the blue/green region of the spectrum and emitting in the green/red have been synthesized (as the form of dyads-pentads), studied by spectrofluorimetry, and used for cellular imaging. The synthesis of phthalocyanine-pyrene 1 was achieved by cyclotetramerization of pyrenyldicyanobenzene, whereas phthalocyanine-BODIPY 2c was synthesized by Sonogashira coupling between tetraiodophthalocyanine and meso-alkynylBODIPY. The standard four-steps BODIPY synthesis was applied to the BODIPY-pyrene dyad 3 starting from pyrenecarbaldehyde and dimethylpyrrole.

In vitro and in vivo trackable titanocene-based complexes using optical imaging or SPECT.

A novel Ti/In-heterometallic radiotheranostic along with non-radioactive Ti/In, Ti/Lu, and Ti/Y analogues has been reported, thanks to the design of a challenging synthesis of the first titanocene-DOTA ligand. The corresponding titanocene-BODIPY complex was developed for in vitro tracking by optical imaging. The different complexes were characterized and their antiproliferative properties were evaluated on three cancer cell lines (A2780, B16F1, and PC3).

Gold(i)-BODIPY-imidazole bimetallic complexes as new potential anti-inflammatory and anticancer trackable agents.

Two new gold(i)-BODIPY-imidazole based trackable therapeutic bimetallic complexes have been synthesized and fully characterized. They display strong antiproliferative properties on several types of cancers including colon, breast, and prostate and one of them presents a significant anti-inflammatory effect. Additionally, the two compounds could be visualised in vitro by confocal microscopy in the submicromolar range.

Near-Infrared-Emitting BODIPY-trisDOTA(111) In as a Monomolecular Multifunctional Imaging Probe: From Synthesis to In Vivo Investigations.

A new generation of monomolecular imaging probes (MOMIP) based on a distyryl-BODIPY (BODIPY=boron-dipyrromethene) coupled with three DOTA macrocycles has been prepared (DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). The MOMIP presents good fluorescence properties and is very stable in serum. The bimodal probe was conjugated to trastuzumab, and an optical in vivo study showed high accumulation of the imaging agent at the tumor site.

Development of trackable metal-based drugs: new generation of therapeutic agents.

In medicinal chemistry, the aim is not only to conceive ever more efficient molecules, but also to understand their mechanism of action. In very recent years, a new promising strategy was developed to tackle this issue: the conception of trackable therapeutic agents. Metal-based drugs are ideal to exploit this expanding area of research.