Chalk River Laboratories

About: Chalk River Laboratories is a based out in . It is known for research contribution in the topics: Neutron diffraction & Neutron scattering. The organization has 2297 authors who have published 2700 publications receiving 73287 citations.

Demonstration of Very High Detritiation Factors with a Pilot-Scale CECE Facility

Abstract: Analysis of process data from initial detritiation tests in a pilot-scale Combined Electrolysis and Catalytic Exchange (CECE) Facility1 indicated that very high detritiation factors (DFs), at least...

Low dose IR-induced IGF-1-sCLU expression: A p53-repressed expression cascade that interferes with TGFβ1 signaling to confer a pro-survival bystander effect

Abstract: Inadvertent mammalian tissue exposures to low doses of ionizing radiation (IR) after radiation accidents, remediation of radioactive-contaminated areas, space travel or a dirty bomb represent an interesting trauma to an organism. Possible low-dose IR-induced bystander effects could impact our evaluation of human health effects, as cells within tissue are not equally damaged after doses of IR ⩽10 cGy. To understand tissue responses after low IR doses, we generated a reporter system using the human clusterin promoter fused to firefly luciferase (hCLUp-Luc). Secretory clusterin (sCLU), an extracellular molecular chaperone, induced by low doses of cytotoxic agents, clears cell debris. Low-dose IR (⩾2 cGy) exposure induced hCLUp-Luc activity with peak levels at 96 h, consistent with endogenous sCLU levels. As doses increased (⩾1 Gy), sCLU induction amplitudes increased and time-to-peak response decreased. sCLU expression was stimulated by insulin-like growth factor-1, but suppressed by p53. Responses in transgenic hCLUp-Luc reporter mice after low IR doses showed that specific tissues (that is, colon, spleen, mammary, thymus and bone marrow) of female mice induced hCLUp-Luc activity more than male mice after whole body (⩾10 cGy) irradiation. Tissue-specific, non-linear dose- and time-responses of hCLUp-Luc and endogenous sCLU levels were noted. Colon maintained homeostatic balance after 10 cGy. Bone marrow responded with delayed, but prolonged and elevated expression. Intraperitoneal administration of α-transforming growth factor (TGF)β1 (1D11), but not control (13C4) antibodies, immediately following IR exposure abrogated CLU induction responses. Induction in vivo also correlated with Smad signaling by activated TGFβ1 after IR. Mechanistically, media with elevated sCLU levels suppressed signaling, blocked apoptosis and increased survival of TGFβ1-exposed tumor or normal cells. Thus, sCLU is a pro-survival bystander factor that abrogates TGFβ1 signaling and most likely promotes wound healing.

Synthesis and Evaluation of a Macrocyclic Actinium-225 Chelator, Quality Control and In Vivo Evaluation of 225 Ac-crown-αMSH Peptide.

Abstract: Targeted alpha-therapy (TAT) has great potential for treating a broad range of late-stage cancers by delivering a focused and lethal radiation dose to tumors Actinium-225 (225 Ac) is an emerging alpha emitter suitable for TAT; however, the availability of chelators for Ac remains limited to a small number of examples (DOTA and macropa) Herein, we report a new Ac macrocyclic chelator named 'crown', which binds quantitatively and rapidly (<10 min) to Ac at ambient temperature We synthesized 225 Ac-crown-αMSH, a peptide targeting the melanocortin 1 receptor (MC1R), specifically expressed in primary and metastatic melanoma Biodistribution of 225 Ac-crown-αMSH showed favorable tumor-to-background ratios at 2 h post injection in a preclinical model In addition, we demonstrated dramatically different biodistrubution patterns of 225 Ac-crown-αMSH when subjected to different latency times before injection A combined quality control methodology involving HPLC, gamma spectroscopy and radioTLC is recommended