Carolina Aguiar Ferreira

Michigan State University | MSU · Department of Radiology

Pancreatic cancer is highly aggressive, with a median survival time of less than 6 months and a 5-year overall survival rate of around 7%. The poor prognosis of PaCa is largely due to its advanced stage at diagnosis and the lack of efficient therapeutic options. Thus, the development of an efficient, multifunctional PaCa theranostic system is urgen...

With advancement in antibody engineering, the development and characterization of new cancer-specific molecular targets are in the forefront of this PET-antibody combination "revolution". Overexpression of CD146 in different types of tumors, including breast tumor, has been associated with tumor progression and poor prognosis. Non-invasive detectio...

Purpose: Cancer immunotherapy has markedly improved the prognosis of patients with a broad variety of malignancies. However, benefits are weighed against unique toxicities, with immune-related adverse events (irAEs) that are frequent and potentially life-threatening. The diagnosis and management of these events are challenging due to heterogeneity...

Although immune checkpoint inhibitors (ICI) have revolutionized cancer management, patient response can be heterogeneous, and the development of ICI resistance is increasingly reported. Novel treatment strategies are necessary not only to expand the use of ICI to previously unresponsive tumor types but also to overcome resistance. Targeted radionuc...

Nanomedicines are considered next generation therapeutics with advanced therapeutic properties and reduced side effects. Herein, we introduce tailored linear and star-like water-soluble nanosystems as stimuli-sensitive nanomedicines for the treatment of solid tumors or hematological malignancies. The polymer carrier and drug pharmacokinetics were i...

Background The approval of Sipuleucel-T demonstrates the value of antigen-specific vaccination approaches for prostate cancer. We have studied a DNA vaccine specific for the ligand-binding domain of the androgen receptor (pTVG-AR) as a more scalable vaccination approach, though its efficacy is limited by the immunosuppressive prostate microenvironm...

An immunosuppressive tumor microenvironment has hampered the efficacy of immunotherapy in prostate cancer. However, radiation-induced immunological effects can partly mediate anti-tumor effects by promoting a pro-inflammatory environment potentially responsive to immunotherapy. Herein, we examined the immunomodulatory properties of a radiopharmaceu...

Purpose The lack of effective molecular biomarkers to monitor idiopathic pulmonary fibrosis (IPF) activity or treatment response remains an unmet clinical need. Herein, we determined the utility of fibroblast activation protein inhibitor for positron emission tomography (FAPI PET) imaging in a mouse model of pulmonary fibrosis. Methods Pulmonary f...

Purpose: New generation of receptor tyrosine kinase inhibitors (RTKIs) have shown to improve survival in many solid tumors. However, an imaging biomarker is needed for patient selection and prediction of treatment response. This study evaluates the use of quantitative changes of HER3 on 68 Ga-NOTA-HER3P1 PET/MRI for prediction of early response to...

Background Systemic radiation treatments that preferentially irradiate cancer cells over normal tissue, known as targeted radionuclide therapy (TRT), have shown significant potential for treating metastatic prostate cancer. Preclinical studies have demonstrated the ability of external beam radiation therapy (EBRT) to sensitize tumors to T cell chec...

Purpose: In preclinical studies, we have demonstrated that delivering low dose radiation to all tumor sites utilizing 90Y-NM600 improves the response to immune checkpoint inhibitors (ICIs). NM600 is an alkylphosphocholine analog that is selectively taken up and retained in murine and human tumors. In this study, the immunomodulatory capacities of t...

Background While checkpoint blockade has been unsuccessful in prostate cancer trials, the approval of Sipuleucel-T demonstrates the value of antigen-specific vaccination approaches for this disease. We have studied a DNA vaccine specific for the ligand-binding domain of the androgen receptor (pTVG-AR) as a more scalable vaccination approach, though...

Irinotecan (IRN) is a semisynthetic derivative of camptothecin that acts as a topoisomerase I inhibitor. IRN is used worldwide for the treatment of several types of cancer, including colorectal cancer, however its use can lead to serious adverse effects, as diarrhea and myelosuppression. Liposomes are widely used as drug delivery systems that can i...

Lymphoma is a heterogeneous disease with varying clinical manifestations and outcomes. Many subtypes of lymphoma, such as Burkitt′s lymphoma and diffuse large B cell lymphoma, are highly aggressive with dismal prognosis even after conventional chemotherapy and radiotherapy. As such, exploring specific biomarkers for lymphoma is of high clinical sig...

The overexpression of CD146 in breast cancer is considered a hallmark of tumor progression and metastasis, particularly in triple negative breast cancer. Aimed at imaging differential CD146 expressions in breast cancer, a noninvasive method for predictive prognosis and diagnosis was investigated using a 64Cu-labeled CD146-specific monoclonal antibo...

Advances in technology and nanomedicine have led to the development of nanoparticles that can be activated for multimodal imaging of cancer, where a stimulus induces a material modification that enhances image contrast. Multimodal imaging using nanomaterials with this capability can combine the advantages and overcome the limitations of any single...

The manifestation of acute kidney injury (AKI) is associated with poor patient outcomes, with treatment options limited to hydration or renal replacement therapies. The onset of AKI is often associated with a surfeit of reactive oxygen species. Here, it is shown that selenium‐doped carbon quantum dots (SeCQDs) have broad‐spectrum antioxidant proper...

Cerenkov radiation (CR) from radionuclides can act as a built‐in light source for cancer theranostics, opening a new horizon in biomedical applications. However, considerably low tumor‐targeting efficiency of existing radionuclides and radionuclide‐based nanomedicines limits the efficacy of CR‐induced theranostics (CRIT). It remains a challenge to...

Design, controlled synthesis, physico-chemical and biological characteristics of novel well-defined biodegradable star-shaped copolymers intended for advanced drug delivery is described. These new biocompatible star copolymers were synthesised by grafting monodispersed semitelechelic linear (sL) N-(2-hydroxypropyl)methacrylamide copolymers onto a 2...

Silver tungstate nanoparticles have been presenting attractive characteristics that could allow its usage in the biomedical sciences. In this study, Ag2WO4 nanoparticles with an average size of 242 nm were obtained and radiolabeled with technetium-99m with high labeling-yield as well as high stability. Biodistribution studies were carried out in he...

The mononuclear phagocyte system (MPS, e.g., liver, spleen) is often treated as a “blackbox” by nanoresearchers in translating nanomedicines. Often, most of the injected nanomaterials are sequestered by the MPS, preventing their delivery to the desired disease areas. Here, this imperfection is exploited by applying nano‐antioxidants with preferenti...

Rapid sequestration and prolonged retention of intravenously injected nanoparticles by the liver and spleen (reticuloendothelial system (RES)) presents a major barrier to effective delivery to the target site and hampers clinical translation of nanomedicine. Inspired by biological macromolecular drugs, synthesis of ultrasmall (diameter ≈12–15 nm) p...

Pertuzumab is clinically employed in the treatment of cancers over-expressing human epidermal growth factor receptor 2 (HER2). Herein, we developed dual-labeled pertuzumab with a radionuclide (89Zr) and a near-infrared fluorophore (IRDye 800CW) to investigate the feasibility of utilizing dual-labeled monoclonal antibodies (mAbs) with numerous imagi...

Radionanomedicine, or the use of radiolabeled nanoparticles in nuclear medicine, has attracted much attention in the last decades. Since the discovery of Cerenkov radiation and its employment in Cerenkov luminescence imaging, the combination of nanomaterials and Cerenkov radiation emitters is revolutionizing the way nanomaterials are perceived in t...

Radionanomedicine, or the use of radiolabeled nanoparticles in nuclear medicine, has attracted much attention in the last decades. Since the discovery of Cerenkov radiation and its employment in Cerenkov luminescence imaging, the combination of nanomaterials and Cerenkov radiation emitters is revolutionizing the way nanomaterials are perceived in t...

Radionanomedicine, or the use of radiolabeled nanoparticles in nuclear medicine, has attracted much attention in the last decades. Since the discovery of Cerenkov radiation and its employment in Cerenkov luminescence imaging, the combination of nanomaterials and Cerenkov radiation emitters is revolutionizing the way nanomaterials are perceived in t...

Porphyrin-based nanomaterials can inherently integrate multiple contrast imaging functionalities with phototherapeutic capabilities. We dispersed Pheophytin (Pheo) into Pluronic F127 and carried out low temperature surfactant-stripping to remove the bulk surfactant. Surfactant-stripped Pheo (ss-Pheo) micelles exhibited similar size, but higher near...

In vivo vagus nerve stimulation holds great promise in regulating food intake for obesity treatment. Here we present an implanted vagus nerve stimulation system that is battery-free and spontaneously responsive to stomach movement. The vagus nerve stimulation system comprises a flexible and biocompatible nanogenerator that is attached on the surfac...

In vivo biomechanical energy harvesting by implanted nanogenerators (i-NG) is promising for self-powered implantable medical devices (IMDs). One critical challenge to reach practical applications is the requirement of continuous direct-current (DC) output, while the low-frequency body activities typically generate discrete electrical pulses. Here,...

The interaction between radionuclides and nanomaterials could generate Cerenkov radiation (CR) for CR-induced photodynamic therapy (PDT) without requirement of external light excitation. However, the relatively week CR interaction leaves clinicians uncertain about the benefits of this new type of PDT. Therefore, a novel strategy to amplify the ther...

Peripheral Arterial Disease (PAD) is a chronic occlusion of lower-extremity arteries distal to the aortic bifurcation attributable to atherosclerosis. PAD is associated with an elevated risk of morbidity and mortality as well as of deterioration of the quality of life with claudication and chronic leg ischemia being the most frequent complications....

Roles of nuclear medicine and molecular imaging in cancer diagnosis and therapy are constantly evolving. Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging allows the investigation of not only morphological but also functional characteristics of tumor tissues and possess distinct advantageous character...

Reactive oxygen and nitrogen species (RONS) are essential for normal physiological processes and play important roles in cell signaling, immunity, and tissue homeostasis. However, excess radical species are implicated in the development and augmented pathogenesis of various diseases. Several antioxidants may restore the chemical balance, but their...

Angiogenesis is widely recognized as one of the hallmarks of cancer. Therefore, imaging and therapeutic agents targeted to angiogenic vessels may be widely-applicable in many types of cancer. To this end, the theranostic isotope pair, ⁸⁶Y and ⁹⁰Y, were used to create a pair of agents for targeted imaging and therapy of neovasculature in murine brea...

Angiogenesis, the complex process of formation of new blood vessels from pre-existing blood vessels, which involves the participation of several pro and anti-angiogenic factors, is implicated in many physiological and pathological conditions. Nanoparticle-based anti-angiogenic activity at the tumor tissue, harnessed by the Enhanced Permeability and...

Purpose: Increased angiogenesis is a marker of aggressiveness in many cancers. Targeted radionuclide therapy of these cancers with angiogenesis-targeting agents may curtail this increased blood vessel formation and slow the growth of tumors, both primary and metastatic. CD105, or endoglin, has a primary role in angiogenesis in a number of cancers,...

A multifunctional core–satellite nanoconstruct is designed by assembling copper sulfide (CuS) nanoparticles on the surface of [⁸⁹Zr]-labeled hollow mesoporous silica nanoshells filled with porphyrin molecules, for effective cancer imaging and therapy. The hybrid nanotheranostic demonstrates three significant features: (1) simple and robust construc...

Despite advances in the development of new therapeutic agents and diagnostic imaging techniques, the 5-year survival of osteosarcoma, the most common type of bone cancer, remains practically unaltered for the last three decades at around 60%. Nanoparticle-based carriers have emerged as new class of drug delivery systems that could potentially overc...

The benefits of intracellular drug delivery from nanomedicine has been limited by biological barriers and to some extent targeting capability. We investigated a size-controlled, dual tumor-mitochondria-targeted theranostic nanoplatform (Porphyrin-PEG Nanocomplexes, PPNs). The maximum tumor accumulation (15.6 %ID/g, 72 h p.i.) and ideal tumor-to-mus...

The benefits of intracellular drug delivery from nanomedicine has been limited by biological barriers and to some extent targeting capability. We investigated a size-controlled, dual tumor-mitochondria-targeted theranostic nanoplatform (Porphyrin-PEG Nanocomplexes, PPNs). The maximum tumor accumulation (15.6 %ID/g, 72 h p.i.) and ideal tumor-to-mus...

Despite recent advances in the development of new therapeutic agents and diagnostic imaging modalities, cancer is still one of the main causes of death worldwide. A better understanding of the molecular signature of cancer has promoted the development of a new generation of anti-cancer drugs and diagnostic agents that specifically target molecular...

Despite efforts, cancer is still one of the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases and 8.2 million cancer-related deaths each year, according to the World Health Organization. Among the strategies to reduce cancer progression and improving its management, implementing early detection technologie...

Bone is a dynamic tissue that is constantly remodeled throughout the lifetime to ensure the integrity of the skeleton. Primary cancer cells disseminate into circulation, often extravasating to bone, where they interact with the bone marrow to grow and proliferate, disrupting the bone homeostasis. Although primary bone tumors account for less than 0...

Objective: Hydroxyapatite is used as a drug-delivery system for bone therapy applications because of its biocompatibility, bioactivity, and osteoconductive properties. In addition, hydroxyapatite nanoparticles (HApN) might be used as a theranostic probe. The aim of this study was to prepare and characterize hydroxyapatite mesoporous nanoparticles,...

Over the last decade, radiolabeled iron oxide nanoparticles have been developed as promising contrast agents for dual-modality positron emission tomography/magnetic resonance imaging (PET/MRI) or single-photon emission computed tomography/magnetic resonance imaging (SPECT/MRI). The combination of PET (or SPECT) with MRI can offer synergistic advant...

To assess the viability and induction of immunotolerance of nonvascularized splenic alloimplants. The phagocytic functions of splenic implants also were studied. Thirty-six adult female New Zealand and California rabbits were used, and these animals were divided into the following 5 groups: (n = 6 / groups 1-4) group 1 (sham operations); group 2 (t...

Bombesin is a tetradecapeptide that binds specifically to gastrin releasing peptide receptors in humans. Several forms of cancer, including lung, prostate, breast, and colon express receptors for bombesin-like peptides. Radiolabeled bombesin analogs with a high affinity for these receptors might therefore be used for scintigraphic imaging of these...

Bombesin (BBN) is a tetradecapeptide that binds specifically to gastrin-releasing peptide receptors. Several forms of cancer, including lung, prostate, breast, and colon express receptors for bombesin-like peptides. Radiolabeled BBN analogs with a high affinity for these receptors might be used for scintigraphic imaging. Kit formulations for labeli...

In the present study, boron nitride nanotubes (BNNTs) were synthesized from an innovative process and functionalized with a glycol chitosan polymer in CDTN (Centro de Desenvolvimento da Tecnologia Nuclear) laboratories. As a means of studying their in vivo biodistribution behavior, these nanotubes were radiolabeled with (99m)Tc and injected in mice...

A bombesin derivative was successfully radiolabeled in high labeling yield. Biodistribution studies and scintigraphic images in Ehrlich tumor-bearing mice were performed. This compound showed high accumulation in tumor tissue with high tumor-to-muscle and tumor-to-blood ratios. Thus, (99m)Tc-HYNIC-Bombesin((7-14)) could be used as an agent for tumo...