Phosphate Compounds in Bone Scanning

Hughes, Sean; Jeyasingh, K.; Lavender, Peter

doi:10.1302/0301-620x.57b2.214

Cited by 11 publications

(3 citation statements)

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“…It has been reported that the blood levels of [ 99m Tc]EHDP decreased over a period of time and the urine level increased. Hughes et al (16), investigating phosphate compounds in rabbits, demonstrated the rapid blood clearance of EHDP compared with that of pyrophosphate or tripolyphosphate. The rapid blood clearance of EHDP compared with that of polyphosphate or pyrophosphate has been confirmed in patients who have undergone bone scanning to detect metastases from breast tumors (8).…”

Section: Discussionmentioning

confidence: 99%

Bone extraction and blood clearance of diphosphonate in the dog

Hughes

Davies

Bassingthwaighte

et al. 1977

American Journal of Physiology-Heart and Circulatory Physiology

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The transcapillary extraction of diphosphonate, as [ 99m Tc]EHDP, a substance used in bone scanning and for management of certain metabolic bone diseases, has been examined. The maximum instantaneous extraction for [ 99m Tc]EHDP was 0.27 ± 0.05 (mean ± SD, N = 10) and the net extraction at 5 min was 0.18 ± 0.05 (N = 10). The permeability ratio of [ 99m Tc]EHDP to the freely diffusible compound, sucrose, using the formula PS = − F s log e (1 − E max ), was 0.71. This is similar to the ratio of diffusion coefficients of EHDP to sucrose, which is estimated to be 0.78. These results suggest that the mechanism by which [ 99m Tc]EHDP passes through the capillaries in bone is passive diffusion. Tissue level estimations of EHDP confirm a rapid blood clearance associated with an increase in the rate of urinary excretion; the level of [ 99m Tc]EHDP in bone, however, remains constant. The fractional excretion of [ 99m Tc]EHDP was 27.3 ± 2.0% in control dogs and was unchanged by thyroparathyroidectomy and subsequent infusion of parathyroid hormone. KeywordsEHDP; capillary extraction; diffusion; bone capillary permeability; indicator-dilution technique; renal clearance; parathyroid hormone; bone scanning; technetium-labeled phosphate compounds; tracer exchange; tissue uptake; blood flow Bone scanning with radioactive isotopes is used with increasing frequency in clinical practice, particularly to detect metastases in bone before they are visible on radiographs (15), to diagnose infections involving bone or joints (2), and to study rates of union of fractures (33).Until recently, the isotopes available for bone scanning included strontium-85 and -87m, and fluorine-18. However, in 1971, Subramanian et al. (31) labeled a polyphosphate with technetium-99m and introduced the phosphate compounds as bone scanning agents. Of the phosphate compounds currently available, technetium-labeled ethane-l-hydroxy-1,1-diphosphonate ([ 99m Tc]-EHDP) appears to be the best (16).EHDP is synthesized from acetic acid and phosphorus trichloride and is injected, labeled with technetium, as a stannous salt. It is stable in vivo and binds by chemi-sorption onto the (18). In therapeutic doses, it inhibits crystal growth, and in patients with osteoporosis large doses of EHDP lead to osteoid formation and to vitamin Ddeficiency rickets (17). Currently, EHDP is being used in the treatment of Paget's disease of bone (27). To reach the hydroxyapatite crystal, [ 99m Tc]EHDP is transported through the capillaries that lie within the Haversian system of the cortex of bone. We have examined the exchange of [ 99m Tc]EHDP across the capillaries in bone, using the indicator-dilution technique. We have also investigated the uptake by the tissues of [ 99m Tc]EHDP, its excretion by the kidneys, and the effect of parathyroid hormone on its renal clearance. Materials and Methods Extraction and permeabilityTen adult male dogs were anesthetized and the nutrient artery of the tibia was approached by the transfibular route. The nutrient artery was cannulated wit...

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Section: Discussionmentioning

confidence: 99%

Bone extraction and blood clearance of diphosphonate in the dog

Hughes

Davies

Bassingthwaighte

et al. 1977

American Journal of Physiology-Heart and Circulatory Physiology

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“…with faster blood clearance. when compared with polyphosphate or pyrophosphate (Dunson et al 1973;Ackerhalt et al 1974;Krishnamurthy et al 1974 ;Hughes et al 1975). Not all reports.…”

Section: Properties Required Of a Bonescanning Agentmentioning

confidence: 99%

Bone Scanning in Clinical Practice

Fogelman¹

1987

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“…Uptake by bone differs between different phosphate compounds and is related to chain lengths for polyphosphate (1,19,20). In rabbits (15) and in man (7) diphosphonates have been shown to have a more rapid blood clearance than pyrophosphate or polyphosphate with a significant improvement in ratio of bone to soft tissue at 4 hr. The exact mechanism of bone localization of the phosphate compounds is not known, however, but it seems that the compounds bind strongly onto the bone surface by chemisorption (18).…”

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The Extraction from the Blood of Phosphate Compounds by Canine Bone

Hughes¹,

Wahner²,

Kelly³

et al. 1979

Nuklearmedizin

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SummaryUptake by bone of 99mTc-labeled pyrophosphate (PPj) and ethane-1-hydroxy-1,1-diphosphonate (EHDP) involves passage through capillaries in the Haversian system, extracellular fluid space, and membrane of osteoblasts before adsorption onto available apatite surfaces. Passage through capillaries was studied by the outflow-dilution technique in a canine tibia model in mongrel dogs. slCr-labeled albumin (nondiffusible reference tracer), sucrose (diffusible reference tracer), PPi, and EHDP were injected into the isolated nutrient tibial artery. Blood was collected from the ipsilateral femoral vein every 15 sec for 2 min. Emax, the apparent extraction at the time of the peaks of the dilution curves, is influenced little by back diffusion; for PP, Emax (mean ± SD) = 0.42 ± 0.08 (N = 4); for EHDP, Emax = 0.27 ± 0.05 (N - 10). Net extraction (apparent fractional retention by (pone at 2 min) was 0.36 ± 0.1 for PP. Emax for 8sSr chloride and 18F sodium in our laboratory is 0.69 ± 0.11 (N = 14) and 0.70 ± 0.008 (N = 9), respectively. Permeabilities (P) were calculated by PS = -Fs loge (1-Emax), where Fs = plasma flow and S = capillary surface; the ratio of P for EHDP to P for sucrose was 0.71 which is similar to the ratio of diffusion coefficients, 0.78. The data suggest that EHDP and probably also PPj pass through the capillaries by passive diffusion. As expected, the extraction through capillary walls for EHDP and PPj was lower than that for 8SSr and 18F because of their larger molecular size.

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Phosphate Compounds in Bone Scanning

Cited by 11 publications

References 11 publications

Bone extraction and blood clearance of diphosphonate in the dog

Bone extraction and blood clearance of diphosphonate in the dog

Bone Scanning in Clinical Practice

The Extraction from the Blood of Phosphate Compounds by Canine Bone

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