Marie-Caline Abadjian

Bio: Marie-Caline Abadjian is an academic researcher from University of Pittsburgh. The author has contributed to research in topics: Cancer & Positron emission tomography. The author has an hindex of 3, co-authored 4 publications receiving 100 citations.

AGuIX® from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine.

Abstract: AGuIX® are sub-5 nm nanoparticles made of a polysiloxane matrix and gadolinium chelates This nanoparticle has been recently accepted in clinical trials in association with radiotherapy This review will summarize the principal preclinical results that have led to first in man administration No evidence of toxicity has been observed during regulatory toxicity tests on two animal species (rodents and monkeys) Biodistributions on different animal models have shown passive uptake in tumours due to enhanced permeability and retention effect combined with renal elimination of the nanoparticles after intravenous administration High radiosensitizing effect has been observed with different types of irradiations in vitro and in vivo on a large number of cancer types (brain, lung, melanoma, head and neck…) The review concludes with the second generation of AGuIX nanoparticles and the first preliminary results on human

Imaging the Tumor Microenvironment.

Abstract: The tumor microenvironment consists of tumor, stromal, and immune cells, as well as extracellular milieu. Changes in numbers of these cell types and their environments have an impact on cancer growth and metastasis. Non-invasive imaging of aspects of the tumor microenvironment can provide important information on the aggressiveness of the cancer, whether or not it is metastatic, and can also help to determine early response to treatment. This chapter provides an overview on non-invasive in vivo imaging in humans and mouse models of various cell types and physiological parameters that are unique to the tumor microenvironment. Current clinical imaging and research investigation are in the areas of nuclear imaging (positron emission tomography (PET) and single photon emission computed tomography (SPECT)), magnetic resonance imaging (MRI) and optical (near infrared (NIR) fluorescence) imaging. Aspects of the tumor microenvironment that have been imaged by PET, MRI and/or optical imaging are tumor associated inflammation (primarily macrophages and T cells), hypoxia, pH changes, as well as enzymes and integrins that are highly prevalent in tumors, stroma and immune cells. Many imaging agents and strategies are currently available for cancer patients; however, the investigation of novel avenues for targeting aspects of the tumor microenvironment in pre-clinical models of cancer provides the cancer researcher with a means to monitor changes and evaluate novel treatments that can be translated into the clinic.

PET and MR imaging with 64Cu/68Ga-labeled AGuIX ultra-small nanoparticles in tumor-bearing mice

Abstract: 1181 Objectives To determine tumor targeting by MRI and PET imaging with ultra-small gadolinium-based nanoparticles, AGuIX, AGuIX-68Ga and AGuIX-NODA-64Cu, in a 4T1 murine breast cancer model. These particles have capabilities to radiosensitive tumors prior to external beam irradiation, and therefore imaging will assist in guiding radiation therapy. Methods Radiolabeling conditions for ultra-small nanoparticles with either 68Ga or 64Cu were optimized for small animal PET imaging. Ten female BALB/c mice were injected subcutaneously above the right shoulder with 1 x 105 4T1 cells and allowed to grow to ~100-500 mm3. Two mice were imaged by MRI immediately after tail vein injection of unlabeled AGuIX nanoparticles. Four mice were imaged by PET/CT at 1, 2, 4, 24 h after injection with AGuIX-NODA-64Cu. And four mice were imaged by PET/CT at 1, 2, 4 h after injection with AGuIX-68Ga. Biodistribution studies were done at the 24 h and 4 h time point for mice injected with AGuIX-NODA-64Cu and AGuIX-68Ga, respectively. Results The radiolabeling yields of these ultra-small nanoparticles were 81-85%. T1-weighted MRI of tumors following i.v. injection showed fast accumulation (within 10 min p.i.) and slow diffusion out of the tumor (over 30 min p.i.). The PET images showed significant accumulation in the tumor, 3.00 ± 0.53% ID/g for AGuIX-NODA-64Cu 24 h p.i. and for 4.59 ± 1.02% ID/g AGuIX-68Ga 4 h p.i. Measurement of radioactivity in major organs ex vivo of AGuIX-NODA-64Cu 24h p.i. gave tumor:muscle ratios of 10.42, and the SUVmax was 2.56. For AGuIX-NODA-64Cu, the kidney had the highest non-target tissue uptake (55.9%ID/gmax at 24 h), with relatively low liver and muscle uptake (4.17 and 0.71%ID/gmax at 24 h, respectively). Conclusions Radiolabeling conditions are being optimized to increase radiochemical yield. The MR images with AGuIX and PET with AGuIX-NODA-64Cu and AGuIX-68Ga nanoparticles showed accumulation in tumors with renal clearance. Optimal nanoparticle uptake into the tumors was from 1 to 4 h post injection as determined by PET/CT imaging. SUPPORT: DOE DE SC0008833, NCI P30CA047904, and S10 RR025098.

Nanoparticles for PET Imaging of Tumors and Cancer Metastasis

Abstract: Positron emission tomography (PET) is a highly translational imaging modality with high sensitivity for oncological imaging. A wide range of classes of nanoparticles have been radiolabeled with a variety of positron-emitting radionuclides; however, the vast majority of nanoparticles have been labeled with longer-lived Cu-64 (T1/2 = 12.7 h) and Zr-89 (T1/2 = 78.4 h), due to their relatively slow clearance from the blood into tumors. PET imaging with nanoparticles has been investigated with agents that passively accumulate in tumors via the enhanced permeation and retention (EPR) effect, and nanoparticles have also been conjugated to targeting agents that include peptides and antibodies (or fragmented constructs thereof) for more active receptor-based tumor targeting. This chapter provides an overview of nanoparticle-based PET agents that have been developed for tumor targeting.

Targeting Tumor Microenvironment for Cancer Therapy.

Abstract: Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in tumor cells result in hyperplasia, uncontrolled growth, resistance to apoptosis, and metabolic shift towards anaerobic glycolysis (Warburg effect). These events create hypoxia, oxidative stress and acidosis within the TME triggering an adjustment of the extracellular matrix (ECM), a response from neighbor stromal cells (e.g., fibroblasts) and immune cells (lymphocytes and macrophages), inducing angiogenesis and, ultimately, resulting in metastasis. Exosomes secreted by TME cells are central players in all these events. The TME profile is preponderant on prognosis and impacts efficacy of anti-cancer therapies. Hence, a big effort has been made to develop new therapeutic strategies towards a more efficient targeting of TME. These efforts focus on: (i) therapeutic strategies targeting TME components, extending from conventional therapeutics, to combined therapies and nanomedicines; and (ii) the development of models that accurately resemble the TME for bench investigations, including tumor-tissue explants, “tumor on a chip” or multicellular tumor-spheroids.

A Nanoparticle Size Series for In Vivo Fluorescence Imaging

Abstract: Any design of nanoparticle vectors for cancer therapy or imaging must take into account the interaction of the nanoparticles with the tumor microenvironment. Size, charge, and shape have been shown to dominate this interaction.[1, 2] In vivo probing of solid tumors with particles of different sizes simultaneously has thus far been challenging due to the limitations of available nano-sized probes.[3–5] Fluorescent dextrans and other macromolecule probes have been used in studies with intravital microscopy, but heterogeneities across samples has prevented their use for the simultaneous imaging of a size series of probes within the same tumour.[5] MRI contrast agents are another attractive set of probes due to the minimally-invasive nature of the technology,[6, 7] but the lower spatial resolution of MRI limits the imaging of heterogeneity within tumors, and the technique does not allow for simultaneous imaging and tracking of a size series of probes within the same tumor.

Nanomaterials for Nanotheranostics: Tuning Their Properties According to Disease Needs.

Abstract: Nanotheranostics is one of the biggest scientific breakthroughs in nanomedicine. Most of the currently available diagnosis and therapies are invasive, time-consuming, and associated with severe toxic side effects. Nanotheranostics, on the other hand, has the potential to bridge this gap by harnessing the capabilities of nanotechnology and nanomaterials for combined therapeutics and diagnostics with markedly enhanced efficacy. However, nanomaterial applications in nanotheranostics are still in its infancy. This is due to the fact that each disease has a particular microenvironment with well-defined characteristics, which promotes deeper selection criteria of nanomaterials to meet the disease needs. In this review, we have outlined how nanomaterials are designed and tailored for nanotheranostics of cancer and other diseases such as neurodegenerative, autoimmune (particularly on rheumatoid arthritis), and cardiovascular diseases. The penetrability and retention of a nanomaterial in the biological system, the therapeutic strategy used, and the imaging mode selected are some of the aspects discussed for each disease. The specific properties of the nanomaterials in terms of feasibility, physicochemical challenges, progress in clinical trials, its toxicity, and their future application on translational medicine are addressed. Our review meticulously and critically examines the applications of nanotheranostics with various nanomaterials, including graphene, across several diseases, offering a broader perspective of this emerging field.

Biodegradable Polymeric Nanoparticles for Drug Delivery to Solid Tumors.

Abstract: Advances in nanotechnology have favored the development of novel colloidal formulations able to modulate the pharmacological and biopharmaceutical properties of drugs. The peculiar physico-chemical and technological properties of nanomaterial-based therapeutics have allowed for several successful applications in the treatment of cancer. The size, shape, charge and patterning of nanoscale therapeutic molecules are parameters that need to be investigated and modulated in order to promote and optimize cell and tissue interaction. In this review, the use of polymeric nanoparticles as drug delivery systems of anticancer compounds, their physico-chemical properties and their ability to be efficiently localized in specific tumor tissues have been described. The nanoencapsulation of antitumor active compounds in polymeric systems is a promising approach to improve the efficacy of various tumor treatments.