Novel PET and Near Infrared Imaging Probes for the Specific Detection of Bacterial Infections Associated With Cardiac Devices.

OBJECTIVES: The aim of this study was to develop imaging agents to detect early stage infections in implantable cardiac devices. BACKGROUND: Bacteria ingest maltodextrins through the specific maltodextrin transporter. We developed probes conjugated with either a fluorescent dye (maltohexaose fluorescent dye probe [MDP]) or a F-18 (F18 fluoromaltohexaose) and determined their usefulness in a model of infections associated with implanted cardiac devices. METHODS: Stainless steel mock-ups of medical devices were implanted subcutaneously in rats. On post-operative day 4, animals were injected with either Staphylococcus aureus around the mock-ups to induce a relatively mild infection or oil of turpentine to induce noninfectious inflammation. Animals with a sterile implant were used as control subjects. On post-operative day 6, either the MDP or F18 fluoromaltohexaose was injected intravenously, and the animals were scanned with the appropriate imaging device. Additional positron emission tomography imaging studies were performed with F18-fluorodeoxyglucose as a comparison of the specificity of our probes (n = 5 to 9 per group). RESULTS: The accumulation of the MDP in the infected rats was significantly increased at 1 h after injection when compared with the control and noninfectious inflammation groups (intensity ratio 1.54 ± 0.07 vs. 1.26 ± 0.04 and 1.20 ± 0.05, respectively; p < 0.05) and persisted for more than 24 h. In positron emission tomography imaging, both F18 fluoromaltohexaose and F18 fluorodeoxyglucose significantly accumulated in the infected area 30 min after the injection (maximum standard uptake value ratio 4.43 ± 0.30 and 4.87 ± 0.28, respectively). In control rats, there was no accumulation of imaging probes near the device. In the noninfectious inflammation rats, no significant accumulation was observed with F18 fluoromaltohexaose, but F18 fluorodeoxyglucose accumulated in the mock-up area (maximum standard uptake value 2.53 ± 0.39 vs. 4.74 ± 0.46, respectively; p < 0.05). CONCLUSIONS: Our results indicate that maltohexaose-based imaging probes are potentially useful for the specific and sensitive diagnosis of infections associated with implantable cardiac devices.

PET imaging of bacterial infections with fluorine-18-labeled maltohexaose.

A positron emission tomography (PET) tracer composed of (18)F-labeled maltohexaose (MH(18)F) can image bacteria in vivo with a sensitivity and specificity that are orders of magnitude higher than those of fluorodeoxyglucose ((18)FDG). MH(18)F can detect early-stage infections composed of as few as 10(5) E. coli colony-forming units (CFUs), and can identify drug resistance in bacteria in vivo. MH(18)F has the potential to improve the diagnosis of bacterial infections given its unique combination of high specificity and sensitivity for bacteria.

Radiohalogenated nonnatural amino acids as PET and SPECT tumor imaging agents.

Radiohalogenated α-amino acids are a diverse and useful class tumor imaging agents suitable for positron emission tomography and single photon emission computed tomography. These tracers target the increased rates of amino acid transport exhibited by many tumor cells. The most established clinical use for radiolabeled amino acids is imaging primary and recurrent gliomas, and there is growing evidence that they may also be useful for other oncologic applications, including neuroendocrine tumors and prostate cancer. This review focuses on the synthesis, radiolabeling, and preclinical evaluation of three series of nonnatural radiohalogenated amino acids: alicyclic, α,α-dialkyl, and 1H-[1,2,3]triazole amino acids which target system L, system A, and cationic amino acid transport systems, respectively.

Template-guided organization of chromonic liquid crystals into micropatterned anisotropic organic solids.

We have developed an approach to generate micropatterns of anisotropic organic materials which exploits the self-organization, driven by pi-stacking and hydrophobic interactions, of an ionic perylenebis(dicarboximide) in aqueous solutions.

Synthesis and studies of the properties of a liquid-crystalline quaterrylenebis(dicarboximide) by 1H NMR and UV-vis spectroscopies.

The synthesis of an ionic quaterrylenebis(dicarboximide) 1a, a long-wavelength absorbing mesogen, is described. When compared with its analogue 2a, an ionic perylenebis(dicarboximide), the aromatic protons of 1a exchange with deuterium of concentrated D(2)SO(4) at a dramatically faster rate. In addition, stronger aggregation in aqueous media was observed for 1a.