MOLECULAR AGENTS FOR TARGETED IMAGING AND THERAPY Trends and Concepts in Agent Development

Abstract: Molecular Imaging allows the visualization of biological processes in vivo, offering new chances for healthcare with respect to early diagnosis and improved therapy. The new field of molecular imaging has been boosted by more sensitive imaging systems and the emergence of targeted imaging agents that home in on molecules of interest. This chapter describes the principles of molecular imaging and the different strategies to design targeted agents. Each imaging modality offers certain strong points but also shortcomings, which impact targeted agent design and their potential area of application

Low Clinical Burden of 2009 Pandemic Influenza A (H1N1) Infection during Pregnancy on the Island of La Réunion

BACKGROUND: Pregnant women have been identified as a group at risk, both for respiratory complications than for the admissions to the Intensive Care Unit (ICU) during the 2009 H1N1 influenza pandemic (pdm). The purpose of this prospective register-based cohort-study was to characterize the clinical virulence of the pdm (H1N1/09)v during pregnancy in La Réunion. METHODS/PRINCIPAL FINDINGS: Over a twelve-week pdm wave (13 July to 3 October 2009), 294 pregnant women presented with an influenza-like illness (ILI) to one of the three maternity departments of the South Reunion area, Indian Ocean. Out of these, 278 were checked by RT-PCR for influenza viruses (157 positive and 121 negative, of whom, 141 with pdm flu and 132 with ILIs of non pdm origin, 5 untyped). The median body temperature was higher in women experiencing pdm flu than in those with non pdm ILI (38.9 degrees C versus 38.3 degrees C, P<0.0001), without evidence linked to circulating viremia. Oseltamivir was given for 86% of pdm flu cases in a median time inferior than 48 hrs (range 0-7 days). The hospitalization rate for pdm flu was of 60% and not associated with underlying conditions. Six viral pneumonia and fourteen asthma attacks were observed among 84 hospitalized pdm flu cases, of whom, only one led to the ICU for an acute lung injury. No maternal death occurred during the pdm wave. None adverse pregnancy outcome was associated with pdm flu. No congenital birth defect, nor early-onset neonatal influenza infection was attributable to pdm flu exposure. CONCLUSIONS/SIGNIFICANCE: This report mitigates substantially the presumed severity of pandemic H1N1/09 influenza infection during pregnancy. The reasons for which the clinical burden of H1N1/09 influenza virus may differ worldwide raise questions about a differential local viral-strain effect and public health preparedness, notably in timely access to special care and antiviral treatments

Chemically triggered drug release from an antibody-drug conjugate leads to potent antitumour activity in mice

Contains fulltext : 191441.pdf (publisher's version ) (Open Access

18 F-labeled analogues of anti-tumor agent calixarene 0118

Calix[4]arene compound 0118 , a topomimetic of the antiangiogenic amphipathic peptide anginex targeting galectin-1, is currently in Phase I clinical trials with terminal cancer patients. Radiolabelled analogues of compound 0118 may serve as a development tool in PK/PD studies of this class of calix[4]arene compounds, and may prove highly valuable for patient stratification and therapy monitoring. So far, such radiotracers have not been described. In this work, we have designed compound 0118 analogues containing a terminal alkyne functional group for introduction of an F-18 label via Cu(I)-catalyzed 1,3-dipolar cycloaddition of 2-[18F]fluoroethylazide

Click to release: instantaneous doxorubicin elimination upon tetrazine ligation

Eliminated without a trace: The fastest click reaction, the highly selective inverse-electron-demand Diels-Alder reaction, has been modified to enable selective bioorthogonal release. Thus, the click reaction of a tetrazine with a drug-bound trans-cyclooctene caused the instantaneous release of the drug and CO2 (see scheme). One possible application is the chemically triggered release, and thereby activation, of a drug from a tumor-bound antibody-drug conjugate

Pretargeting kit for imaging or therapy comprising a trans - cyclooctene dienophile and a diene

Described is a pretargeting method, and related kits, for targeted medical imaging and/or therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention involves the use of [4+2] inverse electron demand (retro) Diels-Alder chemistry in providing the coupling between a Pre-targeting Probe and an Effector Probe. To this end one of these probes comprises an electron-deficient tetrazine or other suitable diene, and the other an E-cyclooctene which has a flattened structure as a result of the position of at least two exocyclic bonds.</p

Tetrazine - trans-cyclooctene chemistry applied to fabricate self-assembled fluorescent and radioactive nanoparticles for in vivo dual mode imaging

Multimodal imaging agents combine two or more imaging modalities into one probe. Self-assembling fluorescent nanoparticles are a promising class of modular multimodal imaging probes as they can allow easy blending of imaging and targeting modalities. Our group recently developed a class of self-assembling and intrinsically fluorescent small molecule-based nanoparticles (SMNPs) with excellent optical properties. In this article, we describe the efficient radiolabeling of these SMNPs via a two-step bioconjugation strategy involving the inverse-electron-demand Diels-Alder ligation between a tetrazine (Tz)-tagged radiolabel and a trans-cyclooctene (TCO)-tagged fluorescent small molecule building block of the SMNPs. Studies in mice revealed that the SMNPs are well tolerated and could be monitored by both radioactivity and fluorescence, thereby demonstrating the potential of SMNPs in optical and dual-mode imaging in vivo. The work also testifies to the utility of the Tz-TCO conjugation chemistry for the labeling of self-assembled nanoparticles