Scintigraphic Imaging of Amyloid Deposits Using Technetium-Labelled Serum Amyloid P Component

1996 ◽  
Vol 90 (s34) ◽  
pp. 18P-18P
Author(s):  
W L Hutchinson ◽  
S J Mather ◽  
M Staltieri ◽  
G E Noble ◽  
D M Vigushin ◽  
...  
Keyword(s):  
Serum Amyloid ◽  
Scintigraphic Imaging ◽  
Amyloid P Component ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Amyloid Deposits ◽  
Amyloid P

Studies with Radiolabelled Serum Amyloid P Component Provide Evidence for Turnover and Regression of Amyloid Deposits In Vivo

1994 ◽  
Vol 87 (3) ◽  
pp. 289-295 ◽  
Author(s):  
Philip N. Hawkins
Keyword(s):  
Amyloid Fibrils ◽  
Specific Binding ◽  
Serum Amyloid ◽  
Poor Correlation ◽  
Amyloid P Component ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Amyloid Deposits ◽  
Amyloid P

1. Quantitative scintigraphic and turnover studies, utilizing the specific binding affinity of serum amyloid P component for amyloid fibrils, have been developed as a tool for evaluating amyloid deposits in vivo. 2. Serial studies in over 300 patients have shown characteristic, diagnostic tissue distributions of amyloid in different types of amyloidosis. There is generally a poor correlation between quantity of amyloid and associated organ dysfunction. 3. Contrary to previous expectations, regression of amyloid has been demonstrated systematically for the first time: AA, AL and variant transthyretin-associated amyloid deposits often regress rapidly, and sometimes completely, if the supply of fibril protein precursors is substantially reduced.

scholarly journals Antibodies to human serum amyloid P component eliminate visceral amyloid deposits

Nature ◽  
2010 ◽  
Vol 468 (7320) ◽  
pp. 93-97 ◽  
Author(s):  
Karl Bodin ◽  
Stephan Ellmerich ◽  
Melvyn C. Kahan ◽  
Glenys A. Tennent ◽  
Andrzej Loesch ◽  
...  
Keyword(s):  
Human Serum ◽  
Serum Amyloid ◽  
Amyloid P Component ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Amyloid Deposits ◽  
Amyloid P

scholarly journals Human serum amyloid P component is an invariant constituent of amyloid deposits and has a uniquely homogeneous glycostructure.

1994 ◽  
Vol 91 (12) ◽  
pp. 5602-5606 ◽  
Author(s):  
M. B. Pepys ◽  
T. W. Rademacher ◽  
S. Amatayakul-Chantler ◽  
P. Williams ◽  
G. E. Noble ◽  
...  
Keyword(s):  
Human Serum ◽  
Serum Amyloid ◽  
Amyloid P Component ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Amyloid Deposits ◽  
Amyloid P

scholarly journals Binding specificity of serum amyloid P component for the pyruvate acetal of galactose.

1984 ◽  
Vol 159 (4) ◽  
pp. 1058-1069 ◽  
Author(s):  
C R Hind ◽  
P M Collins ◽  
D Renn ◽  
R B Cook ◽  
D Caspi ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Binding Specificity ◽  
Serum Amyloid ◽  
Amyloid P Component ◽  
Calcium Dependent ◽  
Protein Ligands ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Amyloid Deposits ◽  
Amyloid P

Serum amyloid P component (SAP) is a normal plasma protein that is of interest because of its presence in amyloid deposits, its presence in normal human glomerular basement membrane, and its stable evolutionary conservation. It has calcium-dependent ligand-binding specificity for amyloid fibrils, fibronectin (Fn), C4-binding protein (C4bp), and agarose. Although the binding to agarose, a linear galactan hydrocolloid derived from some marine algae, is unlikely per se to be related to the physiological function of SAP, it does provide a model system in which to explore the precise ligand requirements of SAP. We report here that the amount of SAP from human, mouse, and plaice (Pleuronectes platessa L.) serum able to bind to agarose from different sources reflect precisely their pyruvate content. Methylation with diazomethane of the carboxyl groups in the pyruvate moiety of agarose completely abolishes SAP binding to agarose. The pyruvate in agarose exists as the 4,6-pyruvate acetal of beta-D-galactopyranose. We have therefore synthesized this galactoside, using a novel procedure, established its structure by analysis of its nuclear magnetic resonance spectra, and shown that it completely inhibits all known calcium-dependent binding reactions of SAP. The R isomer of the cyclic acetal, methyl 4,6-O-(1-carboxyethylidene)-beta-D-galactopyranoside (MO beta DG) was effective at millimolar concentration and was more potent than its noncyclic analogue, while pyruvate, D-galactose, and methyl beta-D-galactopyranoside were without effect. The autologous protein ligands of SAP presumably, therefore express a structural determinant(s) that stereochemically resembles MO beta DG. Availability of this specific, well-characterized, low molecular weight ligand for SAP should facilitate further investigation of the function of SAP and its role in physiological and pathophysiological processes.

Amyloidosis

2020 ◽  
pp. 2218-2234
Author(s):  
Mark B. Pepys ◽  
Philip N. Hawkins
Keyword(s):  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Polarized Light ◽  
Serum Amyloid ◽  
Amyloid P Component ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Amyloid Deposits ◽  
Amyloid P

Amyloidosis is the clinical condition caused by extracellular deposition of amyloid in the tissues. Amyloid deposits are composed of amyloid fibrils, abnormal insoluble protein fibres formed by misfolding of their normally soluble precursors. About 30 different proteins can form clinically or pathologically significant amyloid fibrils in vivo as a result of either acquired or hereditary abnormalities. Small, focal, clinically silent amyloid deposits in the brain, heart, seminal vesicles, and joints are a universal accompaniment of ageing. Clinically important amyloid deposits usually accumulate progressively, disrupting the structure and function of affected tissues and lead inexorably to organ failure and death. There is no licensed treatment which can specifically clear amyloid deposits, but intervention which reduces the availability of the amyloid fibril precursor proteins can arrest amyloid accumulation and may lead to amyloid regression with clinical benefit. Pathology—amyloid fibrils bind Congo red dye producing pathognomonic green birefringence when viewed in high-intensity cross-polarized light, and the protein type can be identified by immunostaining or proteomic analysis. Amyloid deposits always contain a nonfibrillar plasma glycoprotein, serum amyloid P component, the universal presence of which is the basis for use of radioisotope-labelled serum amyloid P component as a diagnostic tracer. Clinicopathological correlation—amyloid may be deposited in any tissue of the body, including blood vessels walls and connective tissue matrix; clinical manifestations are correspondingly diverse. Identification of the amyloid fibril protein is always essential for appropriate clinical management. The specific types of amyloidosis covered in this chapter are reactive systemic (AA) amyloidosis, monoclonal immunoglobulin light chain (AL) amyloidosis, and hereditary systemic amyloidoses (including familial amyloid polyneuropathy).

scholarly journals Repeat doses of antibody to serum amyloid P component clear amyloid deposits in patients with systemic amyloidosis

2018 ◽  
Vol 10 (422) ◽  
pp. eaan3128 ◽  
Author(s):  
Duncan B. Richards ◽  
Louise M. Cookson ◽  
Sharon V. Barton ◽  
Lia Liefaard ◽  
Thirusha Lane ◽  
...  
Keyword(s):  
Extracellular Volume ◽  
Serum Amyloid ◽  
Systemic Amyloidosis ◽  
Whole Body ◽  
Amyloid P Component ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Amyloid Deposits ◽  
Amyloid Load ◽  
Amyloid P

Systemic amyloidosis is a fatal disorder caused by pathological extracellular deposits of amyloid fibrils that are always coated with the normal plasma protein, serum amyloid P component (SAP). The small-molecule drug, miridesap, [(R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC)] depletes circulating SAP but leaves some SAP in amyloid deposits. This residual SAP is a specific target for dezamizumab, a fully humanized monoclonal IgG1 anti-SAP antibody that triggers immunotherapeutic clearance of amyloid. We report the safety, pharmacokinetics, and dose-response effects of up to three cycles of miridesap followed by dezamizumab in 23 adult subjects with systemic amyloidosis (ClinicalTrials.gov identifier:NCT01777243). Amyloid load was measured scintigraphically by amyloid-specific radioligand binding of123I-labeled SAP or of99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid. Organ extracellular volume was measured by equilibrium magnetic resonance imaging and liver stiffness by transient elastography. The treatment was well tolerated with the main adverse event being self-limiting early onset rashes after higher antibody doses related to whole body amyloid load. Progressive dose-related clearance of hepatic amyloid was associated with improved liver function tests.123I-SAP scintigraphy confirmed amyloid removal from the spleen and kidneys. No adverse cardiac events attributable to the intervention occurred in the six subjects with cardiac amyloidosis. Amyloid load reduction by miridesap treatment followed by dezamizumab has the potential to improve management and outcome in systemic amyloidosis.

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