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

Abstract

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 [ 18 F]-IR783-AMBF 3. [ 18 F]-IR783-AMBF 3 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-AMBF 3 was clearly distributed in CSF-containing volumes by PET and fluorescence. We compared IR783-AMBF 3 (fluorescent at 778/793 nm, ex/em) to a shorter-wavelength, fluorescein equivalent (fluorescent at 495/511 nm, ex/ em). IR783-AMBF 3 was superior for its ability to image through blood (hemorrhage) and for imaging CSF-flow, throughskin, in subdural-run lumboperitoneal shunts. IR783-AMBF 3 was safe under the tested dosage both in vitro and in vivo. Conclusion: The superior imaging properties of IR783-AMBF 3 could lead to enhanced accuracy in the treatment of patients and would assist surgeons in non-invasively diagnosing diseases of the CNS.

Cyanine-based [18F]F-C-glycosyl dual imaging probe: synthesis, physico-chemical characterization, in vitro binding evaluation and direct [18F]fluorination

“…The C -glycoside platform and the c(RGDfK) moiety influence neither the absorption/emission wavelengths ( λ abs / λ em = 643/660 nm, Δ s fluo 400 cm −1 ) nor the fluorescence quantum yield ( Φ fluo = 0.13, compared to Cy5.Cl ( Φ fluo = 0.13 in PBS) 45 ). The photophysical properties of this agent 12 are coherent with those of the Cy5 reference 43 making it suitable for bio-imaging experiments. 46…”

“…The C-glycoside platform and the c(RGDfK) moiety influence neither the absorption/ emission wavelengths (l abs /l em = 643/660 nm, D s fluo 400 cm À1 ) nor the fluorescence quantum yield (F fluo = 0.13, compared to Cy5.Cl (F fluo = 0.13 in PBS) 45 ). The photophysical properties of this agent 12 are coherent with those of the Cy5 reference 43 making it suitable for bio-imaging experiments. 46 As described vide supra, the exchange of the iodide counter anion of compound 9 by a triflate (compound 13) induced significant modifications of the chemical shifts of polymethine chain protons of the cyanine in CDCl 3 .…”

“…Such direct radiofluorination of cyanine derivatives was usually described by a [ 18 F]F-B bond formation in soft conditions more compatible with this moiety. [36][37][38][39][40][41][42][43] In the literature, few cyanine derivatives displaying a [ 18 F]F-C bond were described and their radiosyntheses were usually performed by indirect radiofluorination using a prosthetic group. 7,[14][15][16]19,20 Herein, classical radiofluorination method using the K[ 18 F]F-K 222 complex was carried out in acetonitrile at 95 1C for 10 min.…”

PET/Fluorescence Imaging: An Overview of the Chemical Strategies to Build Dual Imaging Tools

“…189 In a third example, AMBF 3 is borne by a functionalized IR783. 182 Radiofluorination is performed by isotopic 19 F/ 18 F exchange in acidic aqueous medium (pH 2 to 2.5) at 80 to 90 °C for 20 min. Contrary to the boronic ester hydrolysis approach, no 19 Ffluoride carrier is needed.…”

“… In a second example, AMBF 3 and a Cy3 derivative are linked together to a nitrogen center of a piperazinium moiety, the second amine function of the piperazine allowing for the conjugation with Dasatinib, a kinase inhibitor . In a third example, AMBF 3 is borne by a functionalized IR783 …”