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Objective: To quantify inorganic pyrophosphate (PPi) production from extracellular adenosine triphosphate (ATP) by human serum or plasma., Methods: Serial measurements of ATP hydrolysis (t1/2) were performed by the luciferase method from a starting concentration of 1 microM in serum or platelet-poor plasma incubated under physiologic conditions. ATP was then pumped into another sample of each specimen using the rate constant derived from the ATP t1/2 of that specimen. Trace (32P) gamma ATP was added at the start of the infusion; conversion to (32P) inorganic orthophosphate (Pi) and to (32P) PPi was determined by precipitation of Pi as reduced phosphomolybdate before and after treatment with yeast pyrophosphatase., Results: ATP was hydrolyzed by all serum and plasma specimens; the rate of hydrolysis in serum and plasma from the same blood sample was nearly identical. PPi was the major product, averaging 71%., Conclusion: PPi is the major product of ATP catabolism in serum and platelet-poor plasma.

Although [99mTc] diethylenetriaminepentaacetic acid (DTPA) is currently the most widely used radioaerosol, rapid alveolar clearance limits its usefulness for single photon emission computed tomography (SPECT) ventilation lung imaging. Previous research has shown that [99mTc]phosphate compounds have high alveolar deposition and slow clearance and thus provide suitable aerosols for pulmonary ventilation studies. We have compared the pulmonary retention and blood levels of [99mTc]pyrophosphate (PYP) and [99mTc]DTPA in eight normal nonsmoking male volunteers. These two radioaerosols have comparable pulmonary deposition. Technetium-99m PYP, however, has a much slower pulmonary clearance which allows sufficient time (20 or more minutes) for SPECT data acquisition using a single-headed rotating gamma camera. While the radiation absorbed dose to the lungs for [99mTc]PYP (0.31 rad/mCi) is greater than for [99mTc]DTPA (0.11 rad/mCi), it is at a clinically acceptable and safe level.

The clearance rate of isotopically labeled synthetic triclinic calcium pyrophosphate dihydrate (CPPD) crystals injection into rabbit joints was estimated by serial counting. Kinetic analysis using a four compartment model showed that half of the injected dose was cleared from 4 rabbit knee joints in 19.1 +/- 0.42 (SEM) days. Profound hypomagnesemia, produced in 2 rabbits with a low magnesium diet, did not affect the rate of crystal clearance detectably. Lavage of joints with solutions known to promote CPPD crystal solubility failed to remove detectable radioactivity. The previous finding of CPPD crystals in synovial phagocytes by electron microscopy, together with the finding of nuclide activity in the synovium and the failure to remove such activity by joint lavage, suggests that endocytosis by synovial cells is an important, effective mechanism controlling the synovial fluid concentration of crystals in patients with CPPD crystal deposition disease.

Synthetic triclinic calcium pyrophosphate dihydrate crystals, uniformly labeled with 85Sr and 45Ca, were injected into the knee joints of 2 normal adult rabbits and 2 rabbits previously injected repeatedly with autologous blood. The "half clearance time" of the injected crystal mass was 20.4 and 19 days from control joints, nearly identical to previously reported values in 6 rabbits (19.1 +/- 1.4), and 28.8 and 34 days from the joints injected with blood, a significant difference (P less than 0.05). Iron stains showed hemosiderin granules in the superficial synovium in these joints. Electron microscopy showed crystals with a molar calcium/phosphorus ratio of 1.0 and particles containing iron within synovial cells. We hypothesize that the decreased clearance rate from hemosiderotic synovium is due to inhibition of one or more intracellular pyrophosphatases by iron.

Synthetic triclinic calcium pyrophosphate dihydrate crystals were uniformly trace-labeled with Ytterbium-169 (169Yb), a pure gamma-emitting isotope with a halflife of 31 days. The solubility of the labeled crystals was similar to that of cold synthetic crystals. The clearance rate of labeled sterile crystals, sieved to obtain the desired size, was determined after injection of microgram quantities into 4 arthritic huuman and 3 normal adult rabbit joints and corrected by the observed rate of clearance of free 169Yb. The derived rate constants were then used to calculate the time required for half of the injected dose of CPPD to be cleared from the joint. Crystal clearance was found in all instances. Crystal removal from normal rabbit joints was much more rapid than from the much larger human arthritic joints and was inversely proportional to the size of the crystals injected.