Perfusion Studies with Technetium-99m Human Albumin Microspheres (HAM)

Ja, Burdine; Re, Sonnemaker; La, Ryder; Hj, Spjut

doi:10.1148/95.1.101

Cited by 24 publications

(4 citation statements)

References 2 publications

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“…The latter have proven very safe and can be easily and strongly labeled with " T cm [15]. On the other hand, albumin microspheres, although they have some good characteristics, cannot be strongly labeled, and the labeling efficiency is only about 60% which requires successive wash-ups to eliminate free " T cm [16]. Perfusion lung scintigraphy is an easy and practically innocuous proce dure for the patient; only two fatal cases have been associated with it [17].…”

Section: Lopuz-m Ajanomentioning

confidence: 99%

Indications for Lung Scintigraphy

Lopéz-Majano¹

1975

Respiration

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Perfusion and ventilation lung scintigraphy are indicated: (1) for evaluating regional perfusion and ventilation, (2) for establishing a ratio between ventilation and perfusion in different areas of the lung, (3) when chest surgery is planned (especially for mapping out the extent of resection), (4) when surgery of the upper abdomen is to be performed, and (5) when global function studies are compromised. Regional ventilation and perfusion studies are invaluable in the diagnosis of pulmcnary thromboembolism in which a perfusion defect is accompanied by well-preserved ventilation in the underperfused area. Regional function tests are indicated for evaluating the distribution of ventilation and pulmonary circulation in practically any chronic pulmonary disease, especially when global function studies, such as spirometry, show significant decreases.

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Section: Lopuz-m Ajanomentioning

confidence: 99%

Indications for Lung Scintigraphy

Lopéz-Majano¹

1975

Respiration

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“…Human albumin microspheres (HAM) offer considerable potential in this regard because they are nontoxic, nonantigenic, and biodegradable, and, because of their unique size, show a high selectivity for the lung tissue, where they become trapped in the pulmonary capillary bed after intravenous injection (2)(3)(4). HAM are prepared from a solution of human serum albumin heated in hot vegetable oil.…”

mentioning

confidence: 99%

“…Although these inhibitors would appear to offer promise for the treatment of emphysema, their therapeutic effectiveness would be considerably enhanced if they could be targeted directly to the lungs. As a step in this direction we report here the manner in which the succinoyl peptide chloromethyl ketone (SPCK) succinoyl (Suc)-AlaAla-Pro-ValCH2Cl, which has been shown to be one of the more potent inhibitors of human leukocyte elastase (5) (2)(3)(4), circulatory studies (9), and cardiac output (10). SPCK was synthesized as described (5).…”

mentioning

confidence: 99%

Albumin microspheres as carrier of an inhibitor of leukocyte elastase: potential therapeutic agent for emphysema.

Martodam¹,

Twumasi²,

Liener³

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

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Methods are described for the covalent attachment of succinoyl-Ala-Ala-Pro-ValCH2Cl, an active sitedirected inhibitor of human leukocyte elastase (EC 3.4.21.11), to microspheres of human albumin. (EC 3.4.21.11), an enzyme that has been implicated in lung tissue injury resulting in the development of emphysema (6, 7). Although these inhibitors would appear to offer promise for the treatment of emphysema, their therapeutic effectiveness would be considerably enhanced if they could be targeted directly to the lungs. As a step in this direction we report here the manner in which the succinoyl peptide chloromethyl ketone (SPCK) succinoyl (Suc)-AlaAla-Pro-ValCH2Cl, which has been shown to be one of the more potent inhibitors of human leukocyte elastase (5), may be covalently attached to HAM with the retention of significant inhibitory activity towards this enzyme. Also reported here are the results of preliminary experiments in vio that show that the carrier-borne inhibitor is in fact targeted primarily to the lungs, where about half of the injected dose has a half-life of approximately 17 days. (8) and is currently available in kit form as a carrier of radioactive tracers for diagnostic lung scanning (2-4), circulatory studies (9), and cardiac output (10). SPCK was synthesized as described (5). Ethylenediamine, 5,5'-dithiobis-(2-nitrobenzoic acid), and hexanediamine were purchased from Aldrich; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-acetylglycine from Sigma; ethyleneimine from Pierce; N-acetyl-DL-homocysteine thiolactone from Schwarz/Mann; and iodo[1-'4C]acetic acid and Na125I (carrier-free) from New England Nuclear. All other chemicals were reagent grade available from commercial sources. All aqueous reagents which were used during the course of the derivatization of HAM contained 0.025% Pluronic F-68 (BASF, Wyandotte, MI) in order to prevent the adherence of microspheres to the sides of reaction vessels and to facilitate uniform suspension. MATERIALS AND METHODSThe sequence of reactions involved in the covalent attachment of SPCK to HAM with extended side chains is described in detail in the legend accompanying Fig. 1. Briefly, the exposed carboxyl groups of HAM were first aminoethylated (step 1), and the amino groups so introduced (I), plus any amino groups already exposed on the surface of HAM, were thiolated with N-acetyl-DL-homocysteine thiolactone (step 2). The thiolated derivative (II) was again aminoethylated with ethyleneimine (step 3) to give the amino derivative (III), or with iodoacetate (step 4) to give the carboxyl derivative (IV). The side chain of IV could be further elongated by condensation with hexanediamine (step 5), yielding V. By virtue of the succinoyl group at the NH2 terminus of the peptide, the latter could be condensed with the amino groups of I, III, and V (step 6), thus yielding HAM-inhibitor derivatives denoted as Ii, IIIi, and Vi, respectively.Assay for Enzyme Activity. Human leukocyte elastase was prepared from purulent sputum as described (12) Step 1: 1...

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“…Εις αριθμόν ασθενών έχορηγήθησαν δια τον ελεγχον της κυκλο φορίας δια της πνευμονικής αρτηρίας, ώς ήδη άνεφέθη αί τελευταίως χρησιμοποιούμενοι ραδιενεργοί μικρόσφαιραι έκ λευκωματίνης σε σημασμένοι δια ραδιενεργού τεχνητίου 99m (Tc99m) (7,8,9,20).…”

Section: ροη αιματος δια της πνευμονικης κυκλοφοριαςunclassified

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Perfusion Studies with Technetium-99m Human Albumin Microspheres (HAM)

Cited by 24 publications

References 2 publications

Indications for Lung Scintigraphy

Indications for Lung Scintigraphy

Albumin microspheres as carrier of an inhibitor of leukocyte elastase: potential therapeutic agent for emphysema.

Δυναμική μελέτη της πνευμονικής κυκλοφορίας επί καρδιακών παθήσεων διά της γ - camera

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