Clinical Myocardial Imaging with Nitrogen-13 Ammonia

Harper, Paul V.; Schwartz, Jeffrey; Beck, R.N.; Lathrop, K.A.; Lembares, N.; Krizek, Helen; Gloria, I.V.; Dinwoodie, Robert; McLaughlin, Andrew F.; Stark, Violet J.; Bekerman, Carlos; Hoffer, Paul B.; Gottschalk, Alexander; Resnekov, Leon; Al‐Sadir, Jafar; Mayorga, A. Sánchez; Brooks, Harold L.

doi:10.1148/108.3.613

Cited by 50 publications

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“…It has an extremely short halflife of 10 min and is therefore generated onsite in cyclotrons. 13 N-ammonia has been in use since the 1970s for cardiac PET imaging [364]. It is administered by injection and exists as an equilibrium mixture of 13 NH 3 (minor) and 13 NH + 4 (major) in the bloodstream [365].…”

Section: Group 15: the Nitrogen Family (Pnictogens)mentioning

confidence: 99%

The elements of life and medicines

Chellan

Sadler

2015

Phil. Trans. R. Soc. A.

181

117

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Which elements are essential for human life? Here we make an element-by-element journey through the periodic table and attempt to assess whether elements are essential or not, and if they are, whether there is a relevant code for them in the human genome. There are many difficulties such as the human biochemistry of several so-called essential elements is not well understood, and it is not clear how we should classify elements that are involved in the destruction of invading microorganisms, or elements which are essential for microorganisms with which we live in symbiosis. In general, genes do not code for the elements themselves, but for specific chemical species, i.e. for the element, its oxidation state, type and number of coordinated ligands, and the coordination geometry. Today, the biological periodic table is in a position somewhat similar to Mendeleev's chemical periodic table of 1869: there are gaps and we need to do more research to fill them. The periodic table also offers potential for novel therapeutic and diagnostic agents, based on not only essential elements, but also non-essential elements, and on radionuclides. Although the potential for inorganic chemistry in medicine was realized more than 2000 years ago, this area of research is still in its infancy. Future advances in the design of inorganic drugs require more knowledge of their mechanism of action, including target sites and metabolism. Temporal speciation of elements in their biological environments at the atomic level is a major challenge, for which new methods are urgently needed.

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Section: Group 15: the Nitrogen Family (Pnictogens)mentioning

confidence: 99%

The elements of life and medicines

Chellan

Sadler

2015

Phil. Trans. R. Soc. A.

181

117

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“…The low myocardial uptake of 13N glutamine and glutamic acid was not expected. The high glutamine concentration in the heart (16) and the observation by Harper et al (17) that methionine sulfoximine, an inhibitor of glutamine synthetase, reduced uptake of 13NH3 in the myocardium have implicated glutamine as the metabolite to which 13NH3 is converted in the heart, with glutamic acid as an intermediate.…”

Section: Resultsmentioning

confidence: 99%

Enzymatic Synthesis and Organ Distribution Studies with¹³N-Labeled L-Glutamine and L-Glutamic Acid

Gelbard¹,

Clarke²,

McDonald³

et al. 1975

Radiology

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A method was developed for producing several hundred mCi of 13NH 3 with subsequent enzymatic synthesis of large amounts ot' 13N-labeled glutamine and glutamic acid. Dynamic measurements and quantitative whole body scans demonstrated greater glutamine uptake in the liver region of mongrel dogs than uptake of glutamic acid or NH 3, although all concentrated in the liver to a significant degree. Myocardial uptake of glutamine and glutamic acid was low, while NH 3 was incorporated into the heart, brain, bladder, and kidneys at a greater rate than the amino acids.

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“…13N-Ammonia has been used as a flow marker in myocardial scintigraphy, [1][2][3][4][5][6][7][8] but the ability of this tracer to quantify regional myocardial blood flow has been questioned because 13N uptake and retention depend on metabolic trapping as well as on myocardial perfusion.6, 7 The results of this study indicate that cellular uptake of '3N also depends on the integrity of the plasmalemmal membrane and possibly on an anion exchange system that can be inhibited by stilbene disulfonic acids.…”

Section: Discussionmentioning

confidence: 99%

Kinetics of 13N-ammonia uptake in myocardial single cells indicating potential limitations in its applicability as a marker of myocardial blood flow.

Rauch¹,

Helus²,

Grunze³

et al. 1985

Circulation

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To study kinetics and principles of cellular uptake of '3N-ammonia, a marker of coronary perfusion in myocardial scintigraphy, heart muscle cells of adult rats were isolated by perfusion with collagenase and hyaluronidase. Net uptake of '3N, measured by flow dialysis, reached equilibrium within 20 sec in the presence of sodium bicarbonate and carbon dioxide (pH 7.4, 370 C). Total extraction, 80 sec after the reaction start, was 786 ± 159 ,umol/ml cell volume. Cells destroyed by calcium overload were unable to extract 13N-ammonia. Omission of bicarbonate and carbon dioxide reduced total extraction to 36% of control. '3N-Ammonia uptake could also be reduced by 50 gM 4,4' diisothiocyanostilbene 2,2' disulfonic acid, by 100 ,ug/ml 1-methionine sulfoximine, and by preincubation with 5 gtM free oleic acid. These results indicate that in addition to metabolic trapping by glutamine synthetase, the extraction of 13N-ammonia by myocardial cells is influenced by cell membrane integrity, intracellular-extracellular pH gradient, and possibly an anion exchange system for bicarbonate. For this reason, the uptake of 13N-ammonia may not always provide a valid measurement of myocardial perfusion. Circulation 71, No. 2, 387-393, 1985. 13N-AMMONIA (13N),* a positron-emitting radionuclide, has been used as a marker of myocardial perfusion.' 8 Because cellular extraction of an ideal flow marker must be proportional to regional myocardial blood flow, extraction of such a marker should not be influenced by cell metabolism or cell membrane transport mechanisms. Since myocardial extraction fraction of '3N-ammonia can be significantly reduced when intracellular glutamine synthetase is inhibited,67 the usefulness of this compound as a flow marker has been questioned. This study provides additional data regarding the kinetics and possible role of the plasma membrane in myocardial '3N uptake and retention in isolated adult rat heart cells. Materials and methodsPreparation of myocardial single cells. Male Wistar rats 3 to 4 months old were heparinized and anesthetized by urethane (1.5 mg/g body weight, intraperitoneally). Hearts were extracted and perfused in a nonrecycling manner for 10 min with 35 mM NaCI, 4.75 mM KCl, 1.2 mM KH2PO4, 150 mM sucrose, 25 mM NaHCO3, 10 mM HEPES buffer, 10 mM glucose, and 5 g/liter albumin bovine fraction V (pH 7.4, 370 C, 95% 02/5% CO2).9 A recycling perfusion (25 min) was carried out with the same solution also containing 150 U/ml unpurified collagenase (E.C.3.4.4.19.) and 1000 U/ml hyaluronidase (E.C.3.2.1.36.).At the end of the perfusion the softened heart was sliced into small pieces and reincubated for 10 min in the same enzymecontaining solution; the suspension was filtered through a nylon mesh and centrifuged gently for 2 min at 50 g. The supernatant was removed and the pellet was washed three times in 130 mM NaCl, 4.0 mM KCI, 1.2 mM KH2PO4, 25 mM HEPES buffer, 10 mM glucose, and 20 g/liter albumin bovine fraction V (pH 7.4, room temperature, 100% 02). A small population of completely destr...

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Clinical Myocardial Imaging with Nitrogen-13 Ammonia

Cited by 50 publications

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The elements of life and medicines

The elements of life and medicines

Enzymatic Synthesis and Organ Distribution Studies with¹³N-Labeled L-Glutamine and L-Glutamic Acid

Kinetics of 13N-ammonia uptake in myocardial single cells indicating potential limitations in its applicability as a marker of myocardial blood flow.

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Clinical Myocardial Imaging with Nitrogen-13 Ammonia

Cited by 50 publications

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The elements of life and medicines

The elements of life and medicines

Enzymatic Synthesis and Organ Distribution Studies with13N-Labeled L-Glutamine and L-Glutamic Acid

Kinetics of 13N-ammonia uptake in myocardial single cells indicating potential limitations in its applicability as a marker of myocardial blood flow.

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Product

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Enzymatic Synthesis and Organ Distribution Studies with¹³N-Labeled L-Glutamine and L-Glutamic Acid