Imaging in Pediatric Demyelinating and Inflammatory Diseases of the Brain- Part 1

2015 ◽  
Vol 83 (9) ◽  
pp. 952-964 ◽  
Author(s):  
Sniya Valsa Sudhakar ◽  
Karthik Muthusamy ◽  
Sunithi Mani ◽  
Sridhar Gibikote ◽  
Manohar Shroff
Keyword(s):  
Inflammatory Diseases ◽  
The Brain ◽  
Brain Part

scholarly journals Synthesis and preclinical evaluation of [11C]MTP38 as a novel PET ligand for phosphodiesterase 7 in the brain

2020 ◽  
Author(s):  
Naoyuki Obokata ◽  
Chie Seki ◽  
Takeshi Hirata ◽  
Jun Maeda ◽  
Hideki Ishii ◽  
...  
Keyword(s):  
Arterial Input Function ◽  
Inflammatory Diseases ◽  
Input Function ◽  
Binding Potential ◽  
Dependent Manner ◽  
Reference Tissue ◽  
Molar Activity ◽  
The Brain

AbstractPurposePhosphodiesterase (PDE) 7 is a potential therapeutic target for neurological and inflammatory diseases, although in-vivo visualization of PDE7 has not been successful. In this study, we aimed to develop [11C]MTP38 as a novel positron emission tomography (PET) ligand for PDE7.Methods[11C]MTP38 was radiosynthesized by 11C-cyanation of a bromo precursor with [11C]HCN. PET scans of rat and rhesus monkey brains and in-vitro autoradiography of brain sections derived from these species were conducted with [11C]MTP38. In monkeys, dynamic PET data were analyzed with an arterial input function to calculate the total distribution volume (VT). The non-displaceable binding potential (BPND) in the striatum was also determined by a reference tissue model with cerebellar reference. Finally, striatal occupancy of PDE7 by an inhibitor was calculated in monkeys according to changes in BPND.Results[11C]MTP38 was synthesized with radiochemical purity ≥ 99.4% and molar activity of 38.6 ± 12.6 GBq/μmol. Autoradiography revealed high radioactivity in the striatum and its reduction by non-radiolabeled ligands, in contrast with unaltered autoradiographic signals in other regions. In-vivo PET after radioligand injection to rats and monkeys demonstrated that radioactivity was rapidly distributed to the brain and intensely accumulated in the striatum relative to the cerebellum. Correspondingly, estimated VT values in the monkey striatum and cerebellum were 3.59 and 2.69 mL/cm3, respectively. The cerebellar VT value was unchanged by pretreatment with unlabeled MTP38. Striatal BPND was reduced in a dose-dependent manner after pretreatment with MTP-X, a PDE7 inhibitor. Relationships between PDE7 occupancy by MTP-X and plasma MTP-X concentration could be described by Hill’s sigmoidal function.ConclusionWe have provided the first successful preclinical demonstration of in-vivo PDE7 imaging with a specific PET radioligand. [11C]MTP38 is a feasible radioligand for evaluating PDE7 in the brain and is currently being applied to a first-in-human PET study.

scholarly journals Microbial DNA testing for inflammatory diseases of the brain of uncertain etiology

2014 ◽  
Vol 4 (3) ◽  
pp. 192-198
Author(s):  
C. Takahashi ◽  
M. Mass ◽  
B. Hamilton ◽  
S. H. Guletkin ◽  
D. Bourdette
Keyword(s):  
Inflammatory Diseases ◽  
Dna Testing ◽  
Microbial Dna ◽  
Uncertain Etiology ◽  
The Brain

Inflammatory Diseases of the Brain

1978 ◽  
pp. 131-138 ◽  
Author(s):  
M. G. Dupont ◽  
L. L. Mortelmans ◽  
D. Baleriaux-Waha ◽  
A. Bollaert ◽  
L. Jeanmart
Keyword(s):  
Inflammatory Diseases ◽  
The Brain

scholarly journals Unlocking the secrets of the brain, part II

BioScience ◽  
1997 ◽  
Vol 47 (7) ◽  
pp. 403-408
Author(s):  
Tabitha M. Powledge
Keyword(s):  
The Brain ◽  
Brain Part

Vision and the brain, part I

2003 ◽  
Vol 21 (2) ◽  
pp. xi-xiii
Author(s):  
Jason J.S. Barton ◽  
Matthew Rizzo
Keyword(s):  
The Brain ◽  
Brain Part

Neutralising and binding anti-interferon-β-1 b (IFN-b-1 b) antibodies during IFN-β-1 b treatment of multiple sclerosis

1997 ◽  
Vol 3 (3) ◽  
pp. 184-190 ◽  
Author(s):  
P. Kivisäkk ◽  
GV Alm ◽  
WZ Tian ◽  
D. Matusevicius ◽  
S. Fredrikson ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Solid Phase ◽  
Inflammatory Diseases ◽  
Neurological Diseases ◽  
Resonance Imaging ◽  
Interferon Β ◽  
Lesion Load ◽  
Neutralising Antibodies ◽  
The Brain ◽  
Antibody Secreting Cells

Interferon-β-1b (IFN-β-1b) is an immunomodulatory therapy of multiple sclerosis (MS), reducing the numbers and severity of exacerbations and the total lesion load measured by magnetic resonance imaging of the brain. The benefits of IFN-β-1b could be hampered by the development of neutralising antibodies against the compound. Our results confirmed earlier studies, showing that 42% of MS patients treated with IFN-β-1b for more than 3 months had developed neutralising antibodies. The occurrence of binding anti-IFN-β-1b antibodies, presently not believed to impede the clinical efficacy of IFN-β-1b, were demonstrated by an immunoassay in some patients already after I month of treatment and in 78% after 3 months. The development of binding antibodies seemed to be an early phenomenon, preceding the appearance of neutralising antibodies. Antibodies crossreacting with IFN-β-1a and natural IFN-β were also found in a majority of IFN-β-1b treated patients with high titres of binding antibodies. Employing a solid-phase enzyme-linked immunospot (ELISPOT) assay, 68% of MS patients treated with IFN-β-1b for 1 -23 months had elevated numbers of anti-IFN-β-1b-antibody secreting cells in blood, compared to 18% of untreated MS patients and 20% among patients with other neurological diseases. Thus, our findings confirm that IFN-β-1 b is immunogenic in MS patients. High levels of anti-IFN-β-1b antibody secreting cells were, however, also found in two untreated control patients with inflammatory diseases, suggesting that anti-IFN-β-1b antibodies might also occur spontaneously.

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