Quantitative studies of bone with the use of 18F-fluoride and 99mTc-methylene diphosphonate

Blake, Glen M.; Park-Holohan, So-Jin; Cook, Gary; Fogelman, Ignac

doi:10.1053/snuc.2001.18742

Cited by 257 publications

(197 citation statements)

References 81 publications

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“…(34) Clinical evaluation of bisphosphonate binding using radioactive labels supplement bone accumulation measurements with blood serum levels, urinary pool, or soft-tissue retention of unbound bisphosphonates. (35)(36)(37)(38) Body mass of the mouse will also play a role in bisphosphonate uptake, clearance, and dosing. And, although body mass was not significantly altered in this study, consideration must be given for situations in which significant weight loss may be observed.…”

Section: Discussionmentioning

confidence: 99%

Binding Kinetics of a Fluorescently Labeled Bisphosphonate as a Tool for Dynamic Monitoring of Bone Mineral Deposition In Vivo

Tower

Campbell

Müller

et al. 2014

Journal of Bone and Mineral Research

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Bone mineral deposition during the modeling of new bone and remodeling of old bone can be perturbed by several pathological conditions, including osteoporosis and skeletal metastases. A site-specific marker depicting the dynamics of bone mineral deposition would provide insight into skeletal disease location and severity, and prove useful in evaluating the efficacy of pharmacological interventions. Fluorescent labels may combine advantages of both radioisotope imaging and detailed microscopic analyses. The purpose of this study was to determine if the fluorescent bisphosphonate OsteoSense could detect localized changes in bone mineral deposition in established mouse models of accelerated bone loss (ovariectomy) (OVX) and anabolic bone gain resulting from parathyroid hormone (PTH) treatment. We hypothesized that the early rate of binding, as well as the total amount of bisphosphonate, which binds over long periods of time, could be useful in evaluating changes in bone metabolism. Evaluation of the kinetic uptake of bisphosphonates revealed a significant reduction in both the rate constant and plateau binding after OVX, whereas treatment with PTH resulted in a 36-fold increase in the bisphosphonate binding rate constant compared with untreated OVX controls. Localization of bisphosphonate binding revealed initial binding at sites of ossification adjacent to the growth plate and, to a lesser extent, along more distal trabecular and cortical elements. Micro-computed tomography (CT) was used to confirm that initial bisphosphonate binding is localized to sites of low tissue mineral density, associated with new bone mineral deposition. Our results suggest monitoring binding kinetics based on fluorescently labeled bisphosphonates represents a highly sensitive, site-specific method for monitoring changes in bone mineral deposition with the potential for translation into human applications in osteoporosis and bone metastatic processes and their treatment.

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Section: Discussionmentioning

confidence: 99%

Binding Kinetics of a Fluorescently Labeled Bisphosphonate as a Tool for Dynamic Monitoring of Bone Mineral Deposition In Vivo

Tower

Campbell

Müller

et al. 2014

Journal of Bone and Mineral Research

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“…Radionuclide tracers such as 18 F À bind to newly mineralizing bone, thus serving as markers of bone blood flow and osteoblastic activity. (17) The mechanism of uptake in bone is the deposition of fluoride ions in newly forming hydroxyapatite crystals at sites of bone formation, and hence the component of bone turnover being measured by 18 F À imaging is osteoblastic activity. Equation 1 shows that the value of K i can change in response to a change in bone blood flow (K 1 ) or a change in the fraction of tracer entering the bone ECF compartment going to bone mineral (k 3 /[k 2 þ k 3 ]), or both.…”

Section: Discussionmentioning

confidence: 99%

“…Radionuclide imaging provides a novel method of studying regional bone metabolism. (17) One of the most widely used techniques is 18 F-fluoride positron emission tomography ( 18 F À PET) analyzed using the method described by Hawkins et al (18)(19)(20)(21)(22)(23) In the Hawkins method, the bone time-activity curve ORIGINAL ARTICLE J JBMR and the arterial tracer input function are analyzed using a threecompartment model to derive the regional bone plasma clearance (K i : units mL min À1 mL À1 ).…”

Section: Introductionmentioning

confidence: 99%

“…(17) Plasma clearance is widely used to study organ function, such as the use of glomerular filtration rate (defined as the renal plasma clearance of inulin) to measure kidney function. The use of bone plasma clearance measured using 18 F À PET to study bone formation was validated in two reports that found high correlations between the bone kinetic parameters obtained using 18 F À PET and histomorphometric indices of bone formation and mineral apposition rate.…”

Section: Introductionmentioning

confidence: 99%

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Differential effects of teriparatide on regional bone formation using 18F-fluoride positron emission tomography

Frost

Siddique

Blake

et al. 2010

Journal of Bone and Mineral Research

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Teriparatide increases skeletal mass, bone turnover markers, and bone strength, but local effects on bone tissue may vary between skeletal sites. We used positron emission tomography (PET) to study 18 F-fluoride plasma clearance (K i ) at the spine and standardized uptake values (SUVs) at the spine, pelvis, total hip, and femoral shaft in 18 postmenopausal women with osteoporosis. Subjects underwent a 1-hour dynamic scan of the lumbar spine and a 10-minute static scan of the pelvis and femurs at baseline and after 6 months of treatment with 20 mg/day teriparatide. Blood samples were taken to derive the arterial input function and lumbar spine K i values evaluated using a three-compartment model. SUVs were calculated for the spine, pelvis, total hip, and femoral shaft. After 6 months treatment with teriparatide, spine K i values increased by 24% (p ¼ .0003), while other model parameters were unchanged except for the fraction of tracer going to bone mineral (k 3 /[k 2 þ k 3 ]), which increased by 23% (p ¼ .0006). In contrast to K i , spine SUVs increased by only 3% (p ¼ .84). The discrepancy between changes in K i and SUVs was explained by a 20% decrease in 18 F À plasma concentration. SUVs increased by 37% at the femoral shaft (p ¼ .0019), 20% at the total hip (p ¼ .032), and 11% at the pelvis (p ¼ .070). Changes in bone turnover markers and BMD were consistent with previous trials. We conclude that the changes in bone formation rate during teriparatide treatment as measured by 18 F À PET differ at different skeletal sites, with larger increases in cortical bone than at trabecular sites. ß

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“…Up till now, however, PET has hardly been used in orthopedics. A comparison of PET and gamma camera-based techniques in orthopedic research showed that PET may be better for several reasons, recently summarized by Blake et al (2001).…”

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confidence: 99%

Rapid bone and blood flow formation in impacted morselized allograftsPositron emission tomography (PET) studies on allografts in 5 femoral component revisions of total hip arthroplasty

Sørensen

Ullmark

Långström

et al. 2003

Acta Orthopaedica Scandinavica

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Quantitative studies of bone with the use of 18F-fluoride and 99mTc-methylene diphosphonate

Cited by 257 publications

References 81 publications

Binding Kinetics of a Fluorescently Labeled Bisphosphonate as a Tool for Dynamic Monitoring of Bone Mineral Deposition In Vivo

Binding Kinetics of a Fluorescently Labeled Bisphosphonate as a Tool for Dynamic Monitoring of Bone Mineral Deposition In Vivo

Differential effects of teriparatide on regional bone formation using 18F-fluoride positron emission tomography

Rapid bone and blood flow formation in impacted morselized allograftsPositron emission tomography (PET) studies on allografts in 5 femoral component revisions of total hip arthroplasty

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