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Relationship between bone uptake of 99mTc-pyrophosphate and hydroxyproline in blood and urine.

In a group of hospital patients with various diseases, the urinary hydroxyproline-to-creatinine ratio showed a significant correlation (r = 0.63; p less than 0.001) with the 5-hr bone-to-soft-tissue ratio for 99mTc-pyrophosphate uptake. In patients on chronic hemodialysis, a similar correlation was found between the 5-hr bone-to-soft-tissue ratio and hydroxyproline levels in plasma and serum. The findings suggest that 99mTc-pyrophosphate binding by bone is related to collagen metabolism.

Aged↗

5-Phosphoribosyl 1-pyrophosphate synthetase converts the acyclic nucleoside phosphonates 9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine and 9-(2-phosphonylmethoxyethyl)adenine directly to their antivirally active diphosphate derivatives.

The acyclic nucleoside phosphonates 9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) are potent inhibitors of DNA viruses and retroviruses, respectively. Unlike nucleoside triphosphates, the metabolically active (diphosphorylated) forms of HPMPA and PMEA (designated HPMPApp and PMEApp) are synthesized in a reversible reaction in which the pyrophosphate group of 5-phosphoribosyl 1-pyrophosphate (PRPP) is directly transferred to HPMPA and PMEA by purified PRPP synthetase. In this respect, PRPP synthetase does not act stereospecifically in that it recognizes both the S-enantiomer and the R-enantiomer of HPMPA as substrate. PRPP synthetase also recognizes other acyclic adenine and 2,6-diaminopurine riboside phosphonates as a substrate. It is now imperative to evaluate the potential role of PRPP synthetase, as activating enzyme, in the antiviral action of this type of molecules in intact cells.

Adenine↗

[A quantitative and quanlitative examination of bone metastases by whole body scanning with 99mTc-pyrophosphate (author's transl)].

The purpose of the present work is to "quantify" bone scanning, in order to calculate indices of localized uptake that will make it possible to differentiate between normal and pathological uptake, and approach an etiologicial diagnosis. The authors use an Elscint dual head whole body scanner and an offline video display calculator. The patient is given 8 mc technetium 99m pyrophosphate 4 hours prior to scanning. The whole body count is expressed in thousands of counts multipled by two so that the knee to whole body ratio is close to one, to facilitate comparison of the indices. Results show that the presence of metastases is demonstrated more clearly by using a ratio bone segment to whole body. Quantitative scanning with 99mTc-pyrophosphate makes it possible to: 1) detect bone metastases easily, 2) follow the metastases during treatment, 3) avoid the gross errors that can be made in nomquantitative scanning.

Bone Neoplasms↗

Myocardial scintigraphy with 99mTc-pyrophosphate in 150 coronary care unit patients.

150 patients, admitted to the coronary care unit with suspicion of acute myocardial infarction, received pyrophosphate labelled with 99mTc, 6-120 h after onset of symptoms, mean 24 h, and were examined in the anterior posterior position and in the left anterior oblique position with a mobile gamma camera. Scintigrams were obtained initially at the injection, and then every 15th min during 1h. The scintigrams were evaluated with regard to presence and localization of radionuclide uptake in myocardial area. In 98 patients with a clinical diagnosis of acute myocardial infarction, uptake was found in 95, with good correlation between ECG and scintigraphic localization. 2. patients with myocardial infarction, verified at autopsy, did not show any uptake and 1 patient, surviving the myocardial infarction, also showed negative result. 19 of 26 patients with unstable angina pectoris also exhibited an uptake in the myocardium. 25 of 26 patients with other diagnoses showed no uptake, while in 1 patient an uptake was recorded. It is concluded that with 99mTc-pyrophosphate scintigraphy it is possible to separate ischemic heart disease from other diseases in patients with chest pain.

Adult↗

Technetium-99m-pyrophosphate bone scans in hyperparathyroidism.

Most patients with primary hyperparathyroidism have normal 5-hr bone-to-soft-tissue ratios for 99MTc-pyrophosphate. In contrast, all five patients with advanced secondary hyperparathyroidism in this study showed significant (p less than 0.001) increases of bone uptake. In the early period after parathyroidectomy, there was no quantitative or qualitative change in uptake. A limited decrease of bone uptake was observed only after prolonged periods of observation. In itself, parathyroid activity seems to have little direct influence on bone uptake of 99MTc-pyrophosphate.

Adolescent↗

Technetium-99m-Sn-pyrophosphate pharmaco-kinetics and bone image changes in parathyroid disease.

Skeletal abnormalities in 12 patients with primary hyperparathyroidism, five patients with pseudohypoparathyroidism, and three patients with hypoparathyroidism were studied to compare the diagnostic sensitivity of bone radiologic examination to that of radionuclide studies using 99mTc-Sn-pyrophosphate (99mTc-PPi) a skeletal-seeking radiopharmaceutical. The results were compared with bone mineral content as measrued by the Norland--Cameron densitometer. Kinetic data of the blood disappearance and plasma clearance of 99mTc-PPi were obtained and compared with data of control subjects without evidence of parathyroid disease. Bone imaging with 99mTc-PPi may be more sensitive than routine skeletal radiographs and bone mineral analysis for the evaluation of skeletal abnormalities in patients with parathyroid disfunction. The enhanced plasma clearance of the tracer observed in patients with primary hyperparathyroidism may reflect the direct effect of excessive parathyroid hormone on the renal handling of 99mTc-Sn-pyrophosphate.

Adolescent↗

[Modification of glyceraldehyde-3-phosphate dehydrogenase from rabbit skeletal muscle by [3-(3-bromoacetylpyridinio)-propyl]-adenosine pyrophosphate (author's transl)].

The NAD analogue [3-(3-acetylpyridinio)-propyl]adenosine pyrophosphate forms enzymically inactive complexes with glyceraldehyde-3-phosphate dehydrogemase from yeast and rabbit skeletal muscle. In the latter enzyme four mol of the analogue are bound with equal affinity inhibiting the enzyme in a competitive way: K1 = 0.0 mM as compared to the dissociation constant KD = 0.6 mM. The brominated derivative [3-(3-bromoacetylpyridinio)-propyl]adenosine pyrophosphate is covalently bound to both enzymes causing irreversible loss of enzymic activity. Complete inactivation of the enzyme from muscle required two moles of the analogue per mol of tetramer. The remaining two sites are still able to bind two mol of NAD+ without regain of enzymic activity. In the case of the yeast enzyme four mol of the analogue are bound. Inactivation of the rabbit muscle enzyme is accompanied by the disappearance of two out of four highly reactive sulfhydryl groups; in the yeast enzyme the four active site cysteine residues are still able to react with DTNB, the reactivity being diminished significantly. Hybrid formation between the native enzymes from yeast and skeletal muscle is not affected by the modification of the enzyme. Similarly the sedimentation properties of the covalently modified enzyme are indistinguishable from those of the native molecule. This indicates that both the native and the irreversibly inhibited enzyme are identical regarding their quaternary structure.

Adenosine Diphosphate↗

A comparison of technetium etidronate and pyrophosphate for acute myocardial infarct imaging.

Etidronate and pyrophosphate, labeled with Tc-95m and Tc-99m, were studied in experimentally infarcted mongrel dogs. A distribution study was conducted 2 hr after simultaneous administration of both agents in two groups of dogs. In one group, the injection was made 15 min after release of a 2-hr coronary arterial ligation. Another group was injected 48 hr after release of the ligation. The uptakes for each radiopharmaceutical and the ratio of uptakes for each sample were computed. The data show pyrophosphate to be a superior agent for the imaging of acute myocardial infarcts because of the higher uptake by infarcted myocardium and the greater contrast between infarcted myocardium and neighboring organs.

Acute Disease↗

Pyrophosphate levels and magnesium oxide therapy in osteogenesis imperfecta.

Serum pyrophosphate levels were determined in 52 patients with osteogenesis imperfecta. In 19 patients the levels were increased, in 14 normal and in 19 fluctuated. No correlation with disease severity was evident. By a double blind study it was shown that neither the administration of oral magnesium oxide, nor placebo, affected the serum pyrophosphate level or the clinical course.

Adolescent↗

Nonidentical subunits of p21H-ras farnesyltransferase. Peptide binding and farnesyl pyrophosphate carrier functions.

The protein farnesyltransferase purified from rat brain contains two nonidentical subunits, alpha and beta. The holoenzyme forms a stable complex with [3H]farnesyl pyrophosphate (FPP) that can be isolated by gel filtration. The [3H]FPP is not covalently bound to the enzyme; it is released unaltered when the enzyme is denatured. When incubated with an acceptor such as p21H-ras, the complex transfers [3H]farnesyl from the bound [3H]FPP to the ras protein. This transfer is not sensitive to dilution by unbound FPP, suggesting that the [3H]FPP is bound at a site that leads to direct transfer to the p21H-ras acceptor. Cross-linking studies show that the p21H-ras binds to the lower molecular weight subunit (beta-subunit), raising the possibility that the [3H]FPP binds to the alpha-subunit. If this suggestion can be confirmed, it would invoke a reaction mechanism in which the alpha-subunit acts as a prenyl pyrophosphate carrier that delivers FPP to p21H-ras which is bound to the beta-subunit.

Alkyl and Aryl Transferases↗

[Incorporation of radioactive calcium and technetium pyrophosphate in to bones].

A method is given for simultaneous in vivo measurement of mineral and collagen metabolism of the bone. Accretion rates of 47-calcium as a chlorid into the bone are representative for bone mineralisation and of 99m-technetium labelled pyrophosphate for collagen metabolism. Compartmental models used for analysis are presented. Bone accretion rates are given in mg, or mMol respectively per unit time for the skeleton, by computation of the specific activity of 47-calcium and 99m-Technetium pyrophosphate and rational bone accretion as registered by total body profile scanning technique. The results obtained in five normal volunteers are presented.

Apatites↗

The characteristics of adsorption of pyrophosphate and citrate onto whewellite.

The adsorption of pyrophosphate and citrate to whewellite was measured by solution depletion. At pH 6.5, the concentration for one-half surface coverage CE(1/2) by pyrophosphate is 15 micrometer. The estimated maximum coverage is 37.5 mumoles per m2. The CE (1/2) for citrate is 4 micrometer, and the estimated maximum coverage is 6.42 mumoles per m2.

Adsorption↗

Stimulation of pyrophosphate production in articular cartilage by a platelet-derived factor is independent of mitogenesis.

The disordered production of extracellular inorganic pyrophosphate (PPi) by cartilage contributes to calcium pyrophosphate dihydrate crystal formation and associated diseases. We have previously shown that a factor(s) derived from human platelets markedly stimulates the accumulation of PPi in the media of porcine articular cartilage in organ culture. This is the first known physiologic modifier of PPi production by cartilage. We report herein that platelet derived growth factor (PDGF) is not the platelet factor responsible for PPi stimulation and that the active factor is not mitogenic for chondrocytes. PDGF added to the media of articular cartilage explants in the presence of 0.5% (platelet-poor) plasma (PPP) produces 3.92 +/- 1.6 mumol/L PPi compared with 2.85 +/- 0.7 mumol/L PPi in cartilage exposed to PPP alone. The platelet extract (PE) and PDGF are mitogenic for adult articular chondrocytes in high-density monolayer cultures. Anti-PDGF antibodies block the mitogenic effects of PDGF and PE. The uptake of thymidine labeled with tritium is 157% of control in cells exposed to PE, PPP, and polyclonal goat immunoglobulin G (IgG); 114% of control in cells exposed to PE, PPP, and anti-PDGF antibody; 148% of control in cells treated with PDGF, PPP, and goat IgG; and 98% of control in cells treated with PDGF, PPP, and anti-PDGF antibody. However, anti-PDGF antibody has no effect on PPi accumulation. PPi levels are 17.22 +/- 1.6 mumol/L in media from cartilage treated with PPP, goat IgG, and PE and 17.62 +/- 2.2 mumol/L in cartilage exposed to PE, PPP, and anti-PDGF antibody. We have further characterized the platelet factor responsible for the stimulation of PPi by cartilage. It is not mitogenic for chondrocytes, and it is not PDGF.

Animals↗

[Importance of pyrophosphate-99mTc scintigraphy in the diagnosis of acute myocardial infarct].

Scintigraphy with pyrophosphate 99mTc was performed in 230 patients with various forms of ischemic heart disease and in 15 persons with pain in the region of the heart caused by osteochondrosis of the cervical and thoracic spinal segments or vegetovascular dystonia (control group). It was found that labelled purophosphate accumulated in the myocardium in necrosis of the heart muscle or when coronary insufficiency takes a course in which necrosis of the myocardial cells is quite possible. Positive results of scintigraphy with pyrophosphate 99mTc are not a strict criterion of acute myocardial infarction because they are also encountered in a chronic course of ischemic heart disease and are evidence in this case that "a state of risk" has occurred during the disease.

Acute Disease↗

Use of blood-pool imaging in evaluation of diffuse activity patterns in technetium-99m pyrophosphate myocardial scintigraphy.

It has been suggested that diffuse Tc-99m pyrophosphate precordial activity may be due to persistent blood-pool activity in routine delayed views during myocardial imaging. To answer this question, we reviewed myocardial scintigrams recorded 60--90 min following the injection of 12--15 mCi of Tc-99m pyrophosphate for the presence of diffuse precordial activity, and compared these with early images of the blood pool in 265 patients. Diffuse activity in the delayed images was identified in 48 patients: in 20 with acute myocardial infarction and in 28 with no evidence of it. Comparison of these routine delayed images with early views of the blood pool revealed two types of patterns. In patients with acute infarction, 95% had delayed images that were distinguishable from blood pool either because the activity was smaller than the early blood pool, or by the presence of localized activity superimposed on diffuse activity identical to blood pool. In those without infarction, 93% had activity distribution in routine delayed views matching that in the early blood-pool images. The usefulness of the diffuse TcPPi precordial activity in myocardial infarction is improved when early blood-pool imaging is used to exclude persistence of blood-pool activity as its cause. Moreover, it does not require additional amounts of radioactivity nor complex computer processing, a feature that may be of value in the community hospital using the technique to "rule out" infarction 24--72 hr after onset of suggestive symptoms.

Angina Pectoris↗

Determination of the inorganic pyrophosphate level and its subcellular localization in Chara corallina.

In order to determine the concentration of pyrophosphate (PPi) and its subcellular distribution in Chara corallina, a new method to concentrate PPi from cell extracts was developed. PPi was extracted and concentrated as Ca2P2O7 under alkaline conditions. The amount of PPi in the precipitate was measured using an enzyme system containing pyrophosphate:fructose-6-phosphate 1-phosphotransferase (EC 2.7.1.90) coupled to NADH oxidation in the presence of [ethylene-bis(oxyethylenenitrilo)]tetraacetic acid. The subcellular localization of PPi and inorganic phosphate (Pi) was studied using the intracellular perfusion technique. The relative volumes of the cytoplasm (6.4%) and the vacuole (93.6%) were determined by perfusing Lucifer Yellow CH into the vacuole and by assuming that the Lucifer Yellow CH dead space represented the cytoplasmic volume. The volume of the chloroplast layer was determined microscopically, and it was found that it occupied 10% of the Chara cytoplasm. PPi was present predominantly in the cytosol at a level of 193 microM, while it existed in the vacuole at a level of only 2.20 microM and less than 1 microM in chloroplasts. By contrast, Pi was distributed almost equally in the cytosol (12.0 mM), chloroplasts (16.2 mM), and the vacuole (6.70 mM). The electrochemical potential gradient across the tonoplast for H+ (delta mu H+ = -11.6 to -18.0 KJ/mol) was nearly equal to the free energy release from the hydrolysis of PPi in cytoplasm (delta Gpp = -18.9 KJ/mol), indicating that the H+-translocating inorganic pyrophosphatase can work as a H+ pump in C. corallina.

Chemical Precipitation↗