Diagnostic Radionuclide Imaging of Amyloid: Biological Targeting by Circulating Human Serum Amyloid P Component

Hawkins, Philip N.; Lavender, J. P.; Myers, M. J.; Pepys, Mark B.

doi:10.1016/s0140-6736(88)92235-0

Cited by 193 publications

(88 citation statements)

References 25 publications

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“…Treatment of patients with poor prognostic features can be successful: a 49-year-old man with a performance status of 40% (Karnofsky et al, 1948) (Hawkins et al, 1988). The patient was treated with six cycles of VAD, followed by 6-weekly oral melphalan and prednisolone (MP) and subsequently ox2b-interferon.…”

Section: Resultsmentioning

confidence: 99%

The treatment of nephrotic syndrome caused by primary (light chain) amyloid with vincristine, doxorubicin and dexamethasone

Wardley

Jayson²,

Goldsmith³

et al. 1998

Br J Cancer

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Summary Three out of four patients with primary (light chain) amyloid nephrotic syndrome treated with vincristine, doxorubicin and dexamethasone (VAD) induction obtained a partial response and are alive in continuing remission at 4.1, 6.5 and 9.3 years. These preliminary results are of considerable interest and suggest that prospective evaluation of this regimen is warranted in patients with this condition.

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Section: Resultsmentioning

confidence: 99%

The treatment of nephrotic syndrome caused by primary (light chain) amyloid with vincristine, doxorubicin and dexamethasone

Wardley

Jayson²,

Goldsmith³

et al. 1998

Br J Cancer

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“…1986;Caspi et ai, 1987;Hawkins et ai, 1988aHawkins et ai, . 1988b, The amount of SAP retained correlates with the overall quantity of amyloid in particular tissues or organs (Hawkins et al, 1988a(Hawkins et al, , 1988b. We report here the use of this approach to study the natural history of AA amyloid in the mouse.…”

Section: Introductionmentioning

confidence: 84%

A primed state exists in vivo following histological regression of amyloidosis

Hawkins¹,

Pepys²

1990

Clinical and Experimental Immunology

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SUMMARYUsing a sensitive, quantitative, and non-invasive in vivo method, based on the specific binding of serum amyloid P component to amyloid fibrils, we have directly documented the spontaneous resolution of A A amyloid deposits in mice, and the prolonged existence thereafter ofa primed state of enhanced susceptibility to further amyloid deposition. These results may have important implications for understanding and management of amyloidosis in humans.

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“…In order to overcome these problems we introduced the use of radiolabelled human SAP as a speci¢c, safe, non-invasive, quantitative in vivo tracer for amyloid deposits and have developed it into a routine tool in clinical practice (Hawkins et al 1988(Hawkins et al , 1990aHawkins 1997). We have performed over 2000 studies, and scintigraphy and metabolic turnover studies with labelled SAP have contributed greatly to knowledge of amyloidosis, and especially its diagnosis, monitoring and response to treatment.…”

Section: Systemic Amyloidosis M B Pepys 205mentioning

confidence: 99%

Pathogenesis, diagnosis and treatment of systemic amyloidosis

Pepys

2001

Phil. Trans. R. Soc. Lond. B

203

156

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Amyloidosis is a disorder of protein folding in which normally soluble proteins are deposited as abnormal, insoluble ¢brils that disrupt tissue structure and cause disease. Although about 20 di¡erent unrelated proteins can form amyloid ¢brils in vivo, all such ¢brils share a common cross-b core structure. Some natural wild-type proteins are inherently amyloidogenic, form ¢brils and cause amyloidosis in old age or if present for long periods at abnormally high concentration. Other amyloidogenic proteins are acquired or inherited variants, containing amino-acid substitutions that render them unstable so that they populate partly unfolded states under physiological conditions, and these intermediates then aggregate in the stable amyloid fold. In addition to the ¢brils, amyloid deposits always contain the non-¢brillar pentraxin plasma protein, serum amyloid P component (SAP), because it undergoes speci¢c calcium-dependent binding to amyloid ¢brils. SAP contributes to amyloidogenesis, probably by stabilizing amyloid ¢brils and retarding their clearance. Radiolabelled SAP is an extremely useful, safe, speci¢c, non-invasive, quantitative tracer for scintigraphic imaging of systemic amyloid deposits. Its use has demonstrated that elimination of the supply of amyloid ¢bril precursor proteins leads to regression of amyloid deposits with clinical bene¢t. Current treatment of amyloidosis comprises careful maintenance of impaired organ function, replacement of end-stage organ failure by dialysis or transplantation, and vigorous e¡orts to control underlying conditions responsible for production of ¢bril precursors. New approaches under development include drugs for stabilization of the native fold of precursor proteins, inhibition of ¢brillogenesis, reversion of the amyloid to the native fold, and dissociation of SAP to accelerate amyloid ¢bril clearance in vivo.

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Diagnostic Radionuclide Imaging of Amyloid: Biological Targeting by Circulating Human Serum Amyloid P Component

Cited by 193 publications

References 25 publications

The treatment of nephrotic syndrome caused by primary (light chain) amyloid with vincristine, doxorubicin and dexamethasone

The treatment of nephrotic syndrome caused by primary (light chain) amyloid with vincristine, doxorubicin and dexamethasone

A primed state exists in vivo following histological regression of amyloidosis

Pathogenesis, diagnosis and treatment of systemic amyloidosis

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