Chemical-Rheological Evaluation of the Short-Term and Long-Term Effectiveness of Binder Rejuvenators

Many previous studies have investigated how rejuvenators affect/alter mechanical/chemical characteristics of aged binders. However, it has not been actively examined how the rejuvenated binders will perform for the next round of service after the rejuvenation was made. A better understanding of the short-term and long-term effect of rejuvenating agents in RAP blended asphalt mixtures is necessary to achieve more appropriate selection and use of rejuvenating agents

A near-infrared probe for non-invasively monitoring cerebrospinal fluid flow by F-18-positron emitting tomography and fluorescence

PURPOSE:Knowing the precise flow of cerebrospinal fluid (CSF) is important in the management of multiple neurological diseases. Technology for non-invasively quantifying CSF flow would allow for precise localization of injury and assist in evaluating the viability of certain devices placed in the central nervous system (CNS). METHODS:We describe a near-infrared fluorescent dye for accurately monitoring CSF flow by positron emission tomography (PET) and fluorescence. IR-783, a commercially available near-infrared dye, was chemically modified and radiolabeled with fluorine-18 to give [18F]-IR783-AMBF3. [18F]-IR783-AMBF3 was intrathecally injected into the rat models with normal and aberrant CSF flow and evaluated by the fluorescence and PET/MRI or PET/CT imaging modes. RESULTS:IR783-AMBF3 was clearly distributed in CSF-containing volumes by PET and fluorescence. We compared IR783-AMBF3 (fluorescent at 778/793 nm, ex/em) to a shorter-wavelength, fluorescein equivalent (fluorescent at 495/511 nm, ex/em). IR783-AMBF3 was superior for its ability to image through blood (hemorrhage) and for imaging CSF-flow, through-skin, in subdural-run lumboperitoneal shunts. IR783-AMBF3 was safe under the tested dosage both in vitro and in vivo. CONCLUSION:The superior imaging properties of IR783-AMBF3 could lead to enhanced accuracy in the treatment of patients and would assist surgeons in non-invasively diagnosing diseases of the CNS

A near-infrared probe for non-invasively monitoring cerebrospinal fluid flow by 18F-positron emitting tomography and fluorescence.

PURPOSE:Knowing the precise flow of cerebrospinal fluid (CSF) is important in the management of multiple neurological diseases. Technology for non-invasively quantifying CSF flow would allow for precise localization of injury and assist in evaluating the viability of certain devices placed in the central nervous system (CNS). METHODS:We describe a near-infrared fluorescent dye for accurately monitoring CSF flow by positron emission tomography (PET) and fluorescence. IR-783, a commercially available near-infrared dye, was chemically modified and radiolabeled with fluorine-18 to give [18F]-IR783-AMBF3. [18F]-IR783-AMBF3 was intrathecally injected into the rat models with normal and aberrant CSF flow and evaluated by the fluorescence and PET/MRI or PET/CT imaging modes. RESULTS:IR783-AMBF3 was clearly distributed in CSF-containing volumes by PET and fluorescence. We compared IR783-AMBF3 (fluorescent at 778/793 nm, ex/em) to a shorter-wavelength, fluorescein equivalent (fluorescent at 495/511 nm, ex/em). IR783-AMBF3 was superior for its ability to image through blood (hemorrhage) and for imaging CSF-flow, through-skin, in subdural-run lumboperitoneal shunts. IR783-AMBF3 was safe under the tested dosage both in vitro and in vivo. CONCLUSION:The superior imaging properties of IR783-AMBF3 could lead to enhanced accuracy in the treatment of patients and would assist surgeons in non-invasively diagnosing diseases of the CNS

¹⁸F‑Radiolabeled Panobinostat Allows for Positron Emission Tomography Guided Delivery of a Histone Deacetylase Inhibitor

Histone deacetylase (HDAC) inhibition is becoming an increasingly popular approach to treat cancer, as HDAC overexpression is common in many malignancies. The blood–brain barrier (BBB) prevents systemically delivered drugs from reaching brain at effective concentration, making small-molecule-HDAC inhibition in brain tumors particularly challenging. To circumvent the BBB, novel routes for administering therapeutics are being considered in the clinic, and a need exists for drugs whose deliveries can be directly imaged, so that effective delivery across the BBB can be monitored. We report chemistry for radiolabeling the HDAC inhibitor, panobinostat, with fluoride-18 (compound-<b>1</b>). Like panobinostat, compound <b>1</b> retains nanomolar efficacy in diffuse intrinsic pontine glioma (DIPG IV and XIII) cells (IC₅₀ = 122 and 108 nM, respectively), with lesser activity against U87 glioma. With a favorable therapeutic ratio, <b>1</b> is highly selective to glioma and demonstrates considerably less toxicity toward healthy astrocyte controls (IC₅₀ = 5265 nM). Compound <b>1</b> is stable in aqueous solution at physiological pH (>7 days, fetal bovine serum), and its delivery can be imaged by positron emission tomography (PET). Compound <b>1</b> is synthesized in two steps, and employs rapid, late-stage aqueous isotopic exchange ¹⁸F-radiochemistry. PET is used to image the in vivo delivery of [¹⁸F]-<b>1</b> to the murine central nervous system via convection enhanced delivery