The application of radionuclide therapy for breast cancer.

Radionuclide-mediated diagnosis and therapy have emerged as effective and low-risk approaches to treating breast cancer. Compared to traditional anatomic imaging techniques, diagnostic radionuclide-based molecular imaging systems exhibit much greater sensitivity and ability to precisely illustrate the biodistribution and metabolic processes from a functional perspective in breast cancer; this transitions diagnosis from an invasive visualization to a noninvasive visualization, potentially ensuring earlier diagnosis and on-time treatment. Radionuclide therapy is a newly developed modality for the treatment of breast cancer in which radionuclides are delivered to tumors and/or tumor-associated targets either directly or using delivery vehicles.

Precision Atomistic Structures of Actinium-/Radium-/Barium-Doped Lanthanide Nanoconstructs for Radiotherapeutic Applications.

Lanthanide vanadate (LnVO) nanoconstructs have generated considerable interest in radiotherapeutic applications as a medium for nanoscale-targeted drug delivery. For cancer treatment, LnVO nanoconstructs have shown promise in encapsulating and retaining radionuclides that emit alpha-particles. In this work, we examined the structure formation of LnVO nanoconstructs doped with actinium (Ac) and radium (Ra), both experimentally and using large-scale atomistic molecular dynamics simulations.

Development of Ac-doped biocompatible nanoparticles for targeted alpha therapy.

Targeted alpha therapy (TAT) relies on chemical affinity or active targeting using radioimmunoconjugates as strategies to deliver α-emitting radionuclides to cancerous tissue. These strategies can be affected by transmetalation of the parent radionuclide by competing ions in vivo and the bond-breaking recoil energy of decay daughters. The retention of α-emitting radionuclides and the dose delivered to cancer cells are influenced by these processes.

Observation of a promethium complex in solution.

Lanthanide rare-earth metals are ubiquitous in modern technologies, but we know little about chemistry of the 61st element, promethium (Pm), a lanthanide that is highly radioactive and inaccessible. Despite its importance, Pm has been conspicuously absent from the experimental studies of lanthanides, impeding our full comprehension of the so-called lanthanide contraction phenomenon: a fundamental aspect of the periodic table that is quoted in general chemistry textbooks. Here we demonstrate a stable chelation of the Pm radionuclide (half-life of 2.

Identifying Candidate Biomarkers of Ionizing Radiation in Human Pulmonary Microvascular Lumens Using Microfluidics-A Pilot Study.

The microvasculature system is critical for the delivery and removal of key nutrients and waste products and is significantly damaged by ionizing radiation. Single-cell capillaries and microvasculature structures are the primary cause of circulatory dysfunction, one that results in morbidities leading to progressive tissue and organ failure and premature death. Identifying tissue-specific biomarkers that are predictive of the extent of tissue and organ damage will aid in developing medical countermeasures for treating individuals exposed to ionizing radiation.

Detection and quantification of γ-H2AX using a dissociation enhanced lanthanide fluorescence immunoassay.

Phosphorylation of the histone protein H2AX to form γ-H2AX foci directly represents DNA double-strand break formation. Traditional γ-H2AX detection involves counting individual foci within individual nuclei. The novelty of this work is the application of a time-resolved fluorescence assay using dissociation-enhanced lanthanide fluorescence immunoassay for quantitative measurements of γ-H2AX.

Overcoming Barriers to Radiopharmaceutical Therapy (RPT): An Overview From the NRG-NCI Working Group on Dosimetry of Radiopharmaceutical Therapy.

Radiopharmaceutical therapy (RPT) continues to demonstrate tremendous potential in improving the therapeutic gains in radiation therapy by specifically delivering radiation to tumors that can be well assessed in terms of dosimetry and imaging. Dosimetry in external beam radiation therapy is standard practice. This is not the case, however, in RPT.

Flagellin peptide flg22 gains access to long-distance trafficking in Arabidopsis via its receptor, FLS2.

Diverse pathogen-derived molecules, such as bacterial flagellin and its conserved peptide flg22, are recognized in plants via plasma membrane receptors and induce both local and systemic immune responses. The fate of such ligands was unknown: whether and by what mechanism(s) they enter plant cells and whether they are transported to distal tissues. We used biologically active fluorophore and radiolabeled peptides to establish that flg22 moves to distal organs with the closest vascular connections.

Carbon Nanofiber Arrays: A Novel Tool for Microdelivery of Biomolecules to Plants.

Effective methods for delivering bioprobes into the cells of intact plants are essential for investigating diverse biological processes. Increasing research on trees, such as Populus spp., for bioenergy applications is driving the need for techniques that work well with tree species.

Immunodiagnostic capabilities of anti-free immunoglobulin light chain monoclonal antibodies.

Overproduction of plasma cell-derived monoclonal free kappa or lambda immunoglobulin light chains (FLCs) is a hallmark of multiple myeloma, AL amyloidosis, and light chain deposition disease. Because these components serve as unique cellular and serologic biomarkers, their detection and quantitation has diagnostic, therapeutic, and prognostic import. In this regard, we have developed monoclonal antibodies (mAbs) that specifically recognize the kappa or lambda FLC products of all known human variable and constant region light chain genes.

Mono and bivalent binding of a scFv and covalent diabody to murine laminin-1 using radioiodinated proteins and SPR measurements: effects on tissue retention in vivo.

Phage display techniques identified a scFv, 15-9, which binds to murine laminin-1 and accumulated selectively in tumors. In this study, a covalent diabody was constructed by changing the amino acid residues at positions VH44 and VL100 to cysteine residues so that the diabody form could be stabilized via a disulfide bond. The covalent diabody was expressed in Pichia pastoris and purified by affinity chromatography.

Identification of an antilaminin-1 scFv that preferentially homes to vascular solid tumors.

The tumor vasculature and extracellular matrix make attractive targets for distinguishing solid tumors from normal cells. In solid tumors, the processes of angiogenesis and metastasis potentially give rise to unique epitopes not usually accessible in homeostatic organs. Specific targeting of solid tumors for radioimmunotherapy requires that the targeting agent accumulate rapidly and at high levels at the tumor site.

A diabody that dissociates to monomer forms at low concentration: effects on binding activity and tumor targeting.

A human scFv, 15-9, was selected from a phage display library for binding to murine laminin-1. A diabody was made from the scFv by shortening the linker from 15 to 5 amino acids between the VH and VL sequence. Radioiodinated scFv and diabody were analyzed for size, binding to laminin, and biodistribution in tumor bearing mice.

Phage display selection of scFv to murine endothelial cell membranes.

The diversity of endothelial cells is becoming more apparent and more important in defining vessel systems that supply blood to normal organs and to tumors. Reagents that identify expression of cell surface determinants on these cells are crucial for differentiating among different vessel types. As a first step in this process we have selected a panel of 25 scFvs from a phage display library that bind to the endothelial cell line LEII.

A monoclonal antibody to a carbohydrate epitope expressed on glycolipid and on alpha3beta1 integrin on human esophageal carcinoma.

A mouse monoclonal antibody (MAb-9) produced by immunization with a human esophageal carcinoma cell line, TE-2 (derived from undifferentiated squamous cell carcinoma) reacted specifically with about 30% of esophageal carcinoma cell lines and tissue sections from clinical samples. MAb-9 showed minimal reactivity with normal esophageal tissue. (125)I, fluorescent or gold particle labeled MAb-9 bound to TE-2 cell surfaces.