Proposed <i>in vitro</i> metabolic pathways of MADAM.

<p>Proposed <i>in vitro</i> metabolic pathways of MADAM.</p

Percentages of unchanged [¹¹C]MADAM at various time points after incubation with either rat (RLM) or human (HLM) liver microsomes.

<p>¹ Values reported are (mean ± standard deviation) of three measurements.</p><p>² n.d. not detected.</p><p>³ n.a. not analysed.</p><p>Percentages of unchanged [¹¹C]MADAM at various time points after incubation with either rat (RLM) or human (HLM) liver microsomes.</p

Percentages of unchanged [¹¹C]MADAM after incubation with rat (RLM) or human (HLM) liver microsomes in the presence of carrier at two different concentrations.

<p>¹ Values reported are (mean ± standard deviation) of three measurements.</p><p>t = Incubation time.</p><p>Percentages of unchanged [¹¹C]MADAM after incubation with rat (RLM) or human (HLM) liver microsomes in the presence of carrier at two different concentrations.</p

List of metabolites identified after incubation of MADAM with RLM (incubation time: 30 min) and HLM (incubation time: 60 min).

<p>The retention time, m/z of parent and major fragment ions for each compound are listed.</p

Radio-HPLC chromatograms of rat urine samples after perfusion of (A) [¹¹C]MADAM, (B) [¹¹C]MADAM /MADAM (25 μg) and (C) [¹¹C]MADAM /MADAM (125 μg) for 15 min.

<p>Radio-HPLC chromatograms of rat urine samples after perfusion of (A) [¹¹C]MADAM, (B) [¹¹C]MADAM /MADAM (25 μg) and (C) [¹¹C]MADAM /MADAM (125 μg) for 15 min.</p

MS^E spectra and structures of the synthesized reference compounds.

<p>(A) MADAM, (B) NHMADAM, (C) SOMADAM, (D) NHSOMADAM and (E) SO₂MADAM.</p

Concentrations of MADAM, NHMADAM, SOMADAM, NHSOMADAM produced by HLM and RLM at various incubation times.

<p>Concentrations of MADAM, NHMADAM, SOMADAM, NHSOMADAM produced by HLM and RLM at various incubation times.</p

Chemical structures of MADAM, SOMADAM, SO₂MADAM, NHMADAM and NHSOMADAM.

<p>Chemical structures of MADAM, SOMADAM, SO₂MADAM, NHMADAM and NHSOMADAM.</p

PiB-Conjugated, Metal-Based Imaging Probes: Multimodal Approaches for the Visualization of β‑Amyloid Plaques

In an effort toward the visualization of β-amyloid plaques by in vivo imaging techniques, we have conjugated an optimized derivative of the Pittsburgh compound B (PiB), a well-established marker of Aβ plaques, to DO3A-monoamide that is capable of forming stable, noncharged complexes with different trivalent metal ions including Gd³⁺ for MRI and ¹¹¹In³⁺ for SPECT applications. Proton relaxivity measurements evidenced binding of Gd­(DO3A-PiB) to the amyloid peptide Aβ_1–40 and to human serum albumin, resulting in a two- and four-fold relaxivity increase, respectively. Ex vivo immunohistochemical studies showed that the DO3A-PiB complexes selectively target Aβ plaques on Alzheimer’s disease human brain tissue. Ex vivo biodistribution data obtained for the ¹¹¹In-analogue pointed to a moderate blood–brain barrier (BBB) penetration in adult male Swiss mice (without amyloid deposits) with 0.36% ID/g in the cortex at 2 min postinjection

Parametric (DVR) 18F-DPA-714 images (axial, coronal and sagittal slices) obtained for a healthy volunteer and an ALS patient, respectively.

<p>Note the significant but normal 18F-DPA-714 uptake in nasal epithelium (a tissue rich in TSPO).</p