Low-Dose Hemibody Radiation, a Treatment Option for Recurrent Prostate Cancer: A Phase 2 Single-Arm Trial.

Purpose: Nontargeted low-dose ionizing radiation has been proposed as a cancer therapeutic for several decades; however, questions remain about the duration of hematological changes and optimal dosing regimen. Early studies delivering fractionated low doses of radiation to patients with cancer used varying doses and schedules, which make it difficult to standardize a successful dose and scheduling system for widespread use. The aim of this phase 2 two-stage trial was to determine whether low-dose radiation therapy (LD-RT) reduced prostate-specific antigen (PSA) in patients with recurrent prostate cancer in efforts to delay initiation of conventional therapies that are known to decrease quality of life.

Space Radiation Protection Countermeasures in Microgravity and Planetary Exploration.

Background: Space radiation is one of the principal environmental factors limiting the human tolerance for space travel, and therefore a primary risk in need of mitigation strategies to enable crewed exploration of the solar system.

Methods: We summarize the current state of knowledge regarding potential means to reduce the biological effects of space radiation. New countermeasure strategies for exploration-class missions are proposed, based on recent advances in nutrition, pharmacologic, and immune science.

Early Intervention with a Multi-Ingredient Dietary Supplement Improves Mood and Spatial Memory in a Triple Transgenic Mouse Model of Alzheimer's Disease.

The increasing global burden of Alzheimer's disease (AD) and failure of conventional treatments to stop neurodegeneration necessitates an alternative approach. Evidence of inflammation, mitochondrial dysfunction, and oxidative stress prior to the accumulation of amyloid-β in the prodromal stage of AD (mild cognitive impairment; MCI) suggests that early interventions which counteract these features, such as dietary supplements, may ameliorate the onset of MCI-like behavioral symptoms. We administered a polyphenol-containing multiple ingredient dietary supplement (MDS), or vehicle, to both sexes of triple transgenic (3xTg-AD) mice and wildtype mice for 2 months from 2-4 months of age.

Impact of Ionizing Radiation on the Cardiovascular System: A Review.

Radiation therapy has become one of the main forms of treatment for various types of cancers. Cancer patients previously treated with high doses of radiation are at a greater risk to develop cardiovascular complications later in life. The heart can receive varying doses of radiation depending on the type of therapy and can even reach doses in the range of 17 Gy.

Single CT Scan Prolongs Survival by Extending Cancer Latency in Trp53 Heterozygous Mice.

There is growing concern over the effects of medical diagnostic procedures on cancer risk. Although numerous studies have demonstrated that low doses of ionizing radiation can have protective effects including reduced cancer risk and increasing lifespan, the hypothesis that any radiation exposure increases cancer risk still predominates. In this study, we investigated cancer development and longevity of cancer-prone Trp53 mice exposed at 7-8 weeks of age to a single 10 mGy dose from either a diagnostic CT scan or gamma radiation.

Multiple CT Scans Extend Lifespan by Delaying Cancer Progression in Cancer-Prone Mice.

Computed tomography (CT) scans are a routine diagnostic imaging technique that utilize low-energy X rays with an average absorbed dose of approximately 10 mGy per clinical whole-body CT scan. The growing use of CT scans in the clinic has raised concern of increased carcinogenic risk in patients exposed to ionizing radiation from diagnostic procedures. The goal of this study was to better understand cancer risk associated with low-dose exposures from CT scans.

Biological Response of Positron Emission Tomography Scan Exposure and Adaptive Response in Humans.

The biological effects of exposure to radioactive fluorodeoxyglucose ((18)F-FDG) were investigated in the lymphocytes of patients undergoing positron emission tomography (PET) procedures. Low-dose, radiation-induced cellular responses were measured using 3 different end points: (1) apoptosis; (2) chromosome aberrations; and (3) γH2AX foci formation. The results showed no significant change in lymphocyte apoptosis, or chromosome aberrations, as a result of in vivo (18)F-FDG exposure, and there was no evidence the PET scan modified the apoptotic response of lymphocytes to a subsequent 2 Gy in vitro challenge irradiation.

Quantifying murine bone marrow and blood radiation dose response following (18)F-FDG PET with DNA damage biomarkers.

The purpose of this study was to quantify the poorly understood radiation doses to murine bone marrow and blood from whole-body fluorine 18 ((18)F)-fluorodeoxyglucose (FDG) positron emission tomography (PET), by using specific biomarkers and comparing with whole body external low dose exposures. Groups of 3-5 mice were randomly assigned to 10 groups, each receiving either a different activity of (18)F-FDG: 0-37MBq or whole body irradiated with corresponding doses of 0-300mGy X-rays. Blood samples were collected at 24h and at 43h for reticulocyte micronucleus assays and QPCR analysis of gene expression in peripheral blood leukocytes.

The influence of Trp53 in the dose response of radiation-induced apoptosis, DNA repair and genomic stability in murine haematopoietic cells.

Apoptotic and DNA damage endpoints are frequently used as surrogate markers of cancer risk, and have been well-studied in the Trp53+/- mouse model. We report the effect of differing Trp53 gene status on the dose response of ionizing radiation exposures (0.01-2 Gy), with the unique perspective of determining if effects of gene status remain at extended time points.

Low-dose radiation from 18F-FDG PET does not increase cancer frequency or shorten latency but reduces kidney disease in cancer-prone Trp53+/- mice.

There is considerable interest in the health effects associated with low-level radiation exposure from medical imaging procedures. Concerns in the medical community that increased radiation exposure from imaging procedures may increase cancer risk among patients are confounded by research showing that low-dose radiation exposure can extend lifespan by increasing the latency period of some types of cancer. The most commonly used radiopharmaceutical for positron emission tomography (PET) scans is 2-[(18)F] fluoro-2-deoxy-d-glucose ((18)F-FDG), which exposes tissue to a low-dose, mixed radiation quality: 634 keV β+ and 511 keV γ-rays.

Radiation-induced DNA damage and the relative biological effectiveness of 18F-FDG in wild-type mice.

Clinically, the most commonly used positron emission tomography (PET) radiotracer is the glucose analog 2-[(18)F] fluoro-2-deoxy-D-glucose ((18)F-FDG), however little research has been conducted on the biological effects of (18)F-FDG injections. The induction and repair of DNA damage and the relative biological effectiveness (RBE) of radiation from (18)F-FDG relative to 662 keV γ-rays were investigated. The study also assessed whether low-dose radiation exposure from (18)F-FDG was capable of inducing an adaptive response.

The synthesis, magnetic purification and evaluation of 99mTc-labeled microbubbles.

Introduction: Ultrasound (US) contrast agents based on microbubbles (MBs) are being investigated as platforms for drug and gene delivery. A methodology for determining the distribution and fate of modified MBs quantitatively in vivo can be achieved by tagging MBs directly with (99m)Tc. This creates the opportunity to employ dual-modality imaging using both US and small animal SPECT along with quantitative ex vivo tissue counting to evaluate novel MB constructs.

Evaluation of single amino acid chelate derivatives and regioselective radiolabelling of a cyclic peptide for the urokinase plasminogen activator receptor.

Introduction: The aim of this work was to investigate the relative radiolabelling kinetics and affinity of a series of ligands for the [(99m)Tc(CO)(3)](+) core, both in the absence and in the presence of competing donors. This information was used to select a suitable ligand for radiolabelling complex peptide-based targeting vectors in high yield under mild conditions.

Methods: A series of alpha-N-Fmoc-protected lysine derivatives bearing two heterocyclic donor groups at the epsilon-amine (1a, 2-pyridyl; '1b, quinolyl; '1c, 6-methoxy-2-pyridyl; 1d, 2-thiazolyl; 1e, N-methylimidazolyl; '1f, 3-pyridyl) were synthesized and labelled with (99m)Tc.

Synthesis, radiolabeling, and bio-imaging of high-generation polyester dendrimers.

A series of aliphatic polyester dendrons, generations 1 through 8, were prepared with a core p-toluenesulfonyl ethyl (TSe) ester as an easily removable protecting group that can be efficiently replaced with a variety of nucleophiles. Using amidation chemistry, a tridentate bis(pyridyl)amine ligand which is known to form stable complexes with both Tc(I) and Re(I) was introduced at the dendrimer core. Metalation of the core ligand with (99m)Tc was accomplished for generations 5 through 7, and resulted in regioselective radiolabeling of the dendrimers.

Impacts of low-dose gamma-radiation on genotoxic risk in aquatic ecosystems.

Chinook salmon cells were exposed to gamma radiation and chromosome damage was assessed using the micronucleus assay. The salmon cells were resistant to radiation at all doses compared to human and mammalian cells. We used an indirect approach to determine if prior low dose exposures at environmental dose levels might alter the consequences of radiation exposures to high doses of radiation (adaptive response).

Radiation-induced apoptosis in mouse lymphocytes is modified by a complex dietary supplement: the effect of genotype and gender.

This study examined whether radiation sensitivity measured by lymphocyte apoptosis could be ameliorated by a complex anti-oxidant/anti-ageing dietary supplement. We also examined lymphocytes from both genders of normal (Nr) mice as well as transgenic growth hormone (Tg) mice that express strongly elevated reactive oxygen species processes and a progeroid syndrome of accelerated ageing. We introduce Tg mice as a potentially valuable new model to study radiation sensitivity.

Isostructural fluorescent and radioactive probes for monitoring neural stem and progenitor cell transplants.

A construct for tagging neurospheres and monitoring cell transplantations was developed using a new technology for producing luminescent and radiolabeled probes that have identical structures. The HIV1-Tat basic domain derivatives NAcGRKKRRQRRR(SAACQ)G (SAACQ-1) and [NAcGRKKRRQRRR(Re(CO)3SAACQ)G]+ (ReSAACQ-1) were prepared in excellent yields using the single amino acid chelate-quinoline (SAACQ) ligand and its Re(I) complex and conventional automated peptide synthesis methods. The distribution of the luminescent Re probe, using epifluorescence microscopy, showed that it localized primarily in the cell nucleus with a significant degree of association on the nuclear envelope.

A complex dietary supplement extends longevity of mice.

Key factors implicated in aging include reactive oxygen species, inflammatory processes, insulin resistance, and mitochondrial dysfunction. All are exaggerated in transgenic growth hormone mice (TGM), which display a syndrome resembling accelerated aging. We formulated a complex dietary supplement containing 31 ingredients known to ameliorate all of the above features.

Bridging the gap between in vitro and in vivo imaging: isostructural Re and 99mTc complexes for correlating fluorescence and radioimaging studies.

A bifunctional ligand that is capable of forming Re and 99mTc complexes as complementary fluorescent and radioactive probes was developed. The tridentate bis(quinoline) amine ligand, which is referred to as the SAACQ system, was prepared in a single step from Fmoc protected lysine in high yield. Reaction of the SAACQ ligand with [Re(CO)3Br3]2- resulted in the formation of the SAACQ-(Re(CO)3)+complex which exhibits favorable fluorescence properties including a long lifetime and a large Stoke's shift.