F-Labeled perfluorocarbon droplets for positron emission tomography imaging.

Introduction: Nanoscale perfluorocarbon (PFC) droplets have been used to create imaging agents and drug delivery vehicles. However, development and characterization of new formulations of PFC droplets are hindered because of the lack of simple methods for quantitative and sensitive assessment of whole body tissue distribution and pharmacokinetics of the droplets. To address this issue, a general-purpose method for radiolabeling the inner core of nanoscale perfluorocarbon droplets with a hydrophobic and lipophobic fluorine-18 compound was developed, so that positron emission tomography (PET) and quantitative biodistribution studies can be employed to evaluate PFC nanodroplets in vivo.

Ga-labeled deferoxamine derivatives for imaging bacterial infection: Preparation and screening of functionalized siderophore complexes.

Introduction: Deferoxamine (DFO) is a siderophore that bacteria use to scavenge iron and could serve as a targeting vector to image bacterial infection where current techniques have critical limitations. [Ga]-DFO, which is a mimetic of the corresponding iron complex, is taken up by bacteria in culture, however in vivo it clears too rapidly to allow for imaging of infection. In response, we developed several new DFO derivatives to identify those that accumulate in bacteria, and at sites of infection, and that could potentially have improved pharmacokinetics.

Correction: A 99mTc-Labelled Tetrazine for Bioorthogonal Chemistry. Synthesis and Biodistribution Studies with Small Molecule trans-Cyclooctene Derivatives.

[This corrects the article DOI: 10.1371/journal.pone.

A 99mTc-Labelled Tetrazine for Bioorthogonal Chemistry. Synthesis and Biodistribution Studies with Small Molecule trans-Cyclooctene Derivatives.

A convenient strategy to radiolabel a hydrazinonicotonic acid (HYNIC)-derived tetrazine with 99mTc was developed, and its utility for creating probes to image bone metabolism and bacterial infection using both active and pretargeting strategies was demonstrated. The 99mTc-labelled HYNIC-tetrazine was synthesized in 75% yield and exhibited high stability in vitro and in vivo. A trans-cyclooctene (TCO)-labelled bisphosphonate (TCO-BP) that binds to regions of active calcium metabolism was used to evaluate the utility of the labelled tetrazine for bioorthogonal chemistry.

(125)I-Tetrazines and Inverse-Electron-Demand Diels-Alder Chemistry: A Convenient Radioiodination Strategy for Biomolecule Labeling, Screening, and Biodistribution Studies.

A convenient method to prepare radioiodinated tetrazines was developed, such that a bioorthogonal inverse electron demand Diels-Alder reaction can be used to label biomolecules with iodine-125 for in vitro screening and in vivo biodistribution studies. The tetrazine was prepared by employing a high-yielding oxidative halo destannylation reaction that concomitantly oxidized the dihydrotetrazine precursor. The product reacts quickly and efficiently with trans-cyclooctene derivatives.

Preparation and evaluation of fluorine-18-labeled insulin as a molecular imaging probe for studying insulin receptor expression in tumors.

A convenient emulsion-based labeling method was used to synthesize fluorine-18-labeled insulin specifically B(1)-(4-[(18)F]fluorobenzoyl)insulin ((18)F-4b) in 6% overall radiochemical yield in 240 min. In vitro screening in MCF7 breast cancer cells demonstrated that the nonradioactive analogue (19)F-4a effectively competed with (125)I-insulin for the insulin receptor (IC50 = 10.6 nM) comparable to that for insulin (IC50 = 7.

Synthesis, characterisation, and biodistribution of radioiodinated C-hydroxy-carboranes.

The synthesis, radiolabelling and biodistribution of iodinated C-hydroxy-nido-carborane ligands is described. Microwave heating by using NaF in aqueous ethanol was used to prepare {sodium [7-hydroxy-7,8-dicarba-nido-undecaborate], nido-carboranol} and {sodium [7-hydroxy-7,8-dicarba-nido-undecaborate-8-carboxylic acid], nido-salborin} in 97 and 90 % yield, respectively. Radioiodination of these nido-carboranes was completed by using both (125)I and (123)I, and the products were obtained in high radiochemical purity (>99 %) and yield (72 to 87 %).

Triazole Appending Agent (TAAG): A New Synthon for Preparing Iodine-Based Molecular Imaging and Radiotherapy Agents.

A new prosthetic group referred to as the triazole appending agent (TAAG) was developed as a means to prepare targeted radioiodine-based molecular imaging and therapy agents. Tributyltin-TAAG and the fluorous analogue were synthesized in high yield using simple click chemistry and the products labeled in greater than 95% RCY with (123)I. A TAAG derivative of an inhibitor of prostate-specific membrane antigen was prepared and radiolabeled with (123)I in 85% yield where biodistribution studies in LNCap prostate cancer tumor models showed rapid clearance of the agent from nontarget tissues and tumor accumulation of 20% injected dose g(-1) at 1 h.

p75 neurotrophin receptor protects primary cultures of human neurons against extracellular amyloid beta peptide cytotoxicity.

The cytotoxicity of extracellular amyloid beta peptide (Abeta) has been clearly demonstrated in many cell types. In contrast, primary human neurons in culture are resistant to extracellular Abeta-mediated toxicity. Here, we investigate the involvement of p75 neurotrophin receptor (p75NTR) in Abeta-treated human neurons.

Effect of tumor necrosis factor-alpha converting enzyme (TACE) and metalloprotease inhibitor on amyloid precursor protein metabolism in human neurons.

Tumor necrosis factor-alpha (TNF-alpha) is implicated in inflammatory processes and much effort is being directed at inhibiting the release of TNF-alpha for treatment of inflammatory conditions. In this context, the drug CP-661,631 has been developed to inhibit the TNF-alpha converting enzyme (TACE). However, TACE is also implicated in amyloid precursor protein secretion.