18F-Fluoride Positron Emission Tomography (PET) in Paget's Disease of Bone

2014-07-24 14:25:21 | BioPortfolio


18 F-fluoride Positron emission tomography (PET) is able to demonstrate and quantify the metabolic activity locally in the skeleton (1). This technique should, therefore, also be able to demonstrate a dramatic decrease in the metabolic activity in localized monostotic Paget’s disease lesions after therapy. In this condition, indeed, the usual biological markers may be unhelpful to assess the efficacy of therapy, because they are usually comprised in the normal range for single pagetic localizations, even before therapy (2). The main purpose of this trial is to assess the early and long term response of pagetic bone to bisphosphonate therapy.


I. Background of the subject:

Paget’s disease of bone is a condition characterized by a focal exuberant increase in bone remodeling, resulting in a number of important architectural abnormalities, potentially leading to bone deformity and bone fragility. This condition may be polyostotic or monostotic. Biological markers of bone remodeling, mainly alkaline phosphatase and markers of bone resorption such as urinary hydroxyproline, are commonly utilized to assess Paget’s disease activity.

However, a monostotic Paget’s disease is most frequently accompanied by biological markers still in the normal range (1). Conventional 99mTc MDP bone scan is able to localize the lesion. However, the changes observed with this technique after therapy and when the disease recurs do not help much to guide the clinician (3). Indeed, there can be some improvement on the conventional bone scans whereas on the X-ray films, worsening of the pagetic lesions might simultaneously be observed (4). The recurrence of the condition could also be missed by conventional bone scans (4). Therefore, PET scan using 18 Fluoride should by its metabolic approach be able to demonstrate the local activity of Paget’s disease, to assess the efficacy of active drugs and to evidence the local recurrence of the disease, better than the conventional existing techniques.

II. Experimental approach and methods

1. 20 patients suffering from a Paget’s disease of bone (polyostotic: n = 6; monostotic: n = 14) will be studied prior to and after 1, 6, and 12 months of bisphosphonate therapy. The polyostotic cases will serve to the preliminary feasibility study. A localized Paget’s disease will include isolated Pagetic lesions in bones of the face and or the skull, the spine and of the (lower or upper) limbs.

2. Paget’s disease confirmed by X rays will be quantified by biological parameters of bone remodeling: total alkaline phosphatase, bone specific alkaline phosphatase, serum C-telopeptide (CTX), urinary NTx corrected by creatinine in a morning spot urine after an overnight fast.

3. Routine biological parameters such as creatinine, full blood count, serum calcium, phosphate and magnesium, as well as 25OH vitamin D, 1,25(OH)2 vitamin D and iPTH will also be performed at the start and after therapy. A total duration of 5 years should be considered for the completion of the whole study. 18 Fluoride will be produced by the cyclotron, localized in Louvain-la-Neuve (Belgium).

18F-fluoride is produced by the 18O(p,n) 18F nuclear reaction by bombarding an enriched H218O target with protons. 185 Mbq 18F will be injected.

4. Scans will be performed on a Siemens ECAT HR+ PET scanner. This machine consists of 32 rings of BGO (bismuth germanium oxide) detectors (40.5x43.9x30 mm size) yielding 63 transverse slices (2.425 mm thickness) in a 16.2 cm axial FOV. In 2D mode, the resolution of the HR+ scanner is typically 5.4 mm and 5.0 mm FWHM at 10 cm in the transaxial and axial directions, respectively. A dynamic acquisition centered on pagetic bones will be performed over 60 minutes, starting immediately at tracer injection. Data will be reconstructed by filtered backprojection and iterative methods, with attenuation correction obtained from a transmission scan performed before tracer injection. Dynamic acquisition will allow us to modelize the tracer uptake and calculate the influx constants by means of multi-compartmental analysis. Kinetic modeling has been shown to better discriminate between normal, osteoporotic and Pagetic bones (Cook et al, SNM 2001, Toronto) and we assume that small changes in bone metabolism during therapy will be more precisely assessed by kinetic modeling than by simple semi-quantitative indexes such as standardized uptake values (SUV). Nevertheless, we will prospectively compare different models and SUV measurements to further identify the most appropriate quantification method.

Effective radiation dose equivalent is 0.027 mSv/Mbq 18F-fluoride. Target organ is the urinary bladder wall (due to the urinary excretion of the unbound fraction of the tracer) with an estimated radiation dose of 0.25 mGy/MBq.

III. References

1. Cook GJ, Lodge MA, Blake GM, Marsden PK, Fogelman I. Differences in skeletal kinetics between vertebral and humeral bone measured by 18 F-fluoride positron emission tomography in postmenopausal women. J Bone Miner Res 2000; 15: 763-769.

2. Kanis JA, Gray RES. Long-term follow-up observations on treatment in Paget’s disease of bone. Clin Orthop 1987; 217: 99-125.

3. Smith ML, Fogelman I, Ralston S et al. Correlation of skeletal uptake of 99mTc-diphosphonate and alkaline phosphatase before and after oral diphosphonate therapy in Paget’s disease. Metab Bone Dis Relat Res 1984; 5: 167-170.

4. Merrick MV, Merrick JM. Observations on the natural history of Paget’s disease. Clin Radiol 1985; 36: 169-174.

5. Vellenga CLJR, Pauwels EKJ, Bijvoet OLM et al. Scintigraphic aspects of the recurrence of treated Paget’s disease of bone. J Nucl Med 1985; 54: 273-281.

6. A. Nzeusseu Toukap, M. Lonneux, J. Installe, A. Bolle, G. Depresseux, J.P. Devogelaer.

International Symposium of the National Association for the Relief of Paget’s Disease. St Catherine’s college, 17-18 july 2003, Oxford, UK.

18F-Fluoride Positron Emission Tomography : Preliminary assessment of therapy in Paget’s Disease of Bone.

Study Design

Allocation: Non-Randomized, Control: Active Control, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Paget's Disease of Bone


Bisphosphonate treatment


Rheumatology, Molecular Imaging and Experimental Radiotherapy departments, Saint-Luc University Hospital, Catholic University of




Université Catholique de Louvain

Results (where available)

View Results


Published on BioPortfolio: 2014-07-24T14:25:21-0400

Clinical Trials [1490 Associated Clinical Trials listed on BioPortfolio]

New Bisphosphonate Treatment for Paget's Disease

HORIZON TOP will study the effect of zoledronic acid given once as an iv infusion compared to 60 days of oral risedronate in patients with Paget's disease of bone. The effect will be demo...

Pathophysiology of Paget's Disease of Bone

Paget's disease of the bone is a skeletal disorder which results in increased and disorganized bone remodeling, leading to dense but fragile and expanding bones. The identified genetic cau...

A Research Study to Test the Effectiveness of MK0217 in Patients With Paget's Bone Disease

To test the safety, effectiveness of MK0217 when taken once a week for six months in treating patients with Paget's bone disease.

Re-treatment of Patients With Paget's Disease Using Zoledronic Acid

The purpose of this study is to demonstrate that patients with Paget's disease of the bone who had responded to zoledronic acid treatment as participants in the core registration studies C...

Safety and Efficacy Trial With Zoledronic Acid for the Treatment of Paget's Disease of Bone

The primary objective of this study was to show non-inferiority of zoledronic acid to risedronate, with respect to the proportion of patients who achieved therapeutic response.

PubMed Articles [32918 Associated PubMed Articles listed on BioPortfolio]

A quest for clarity in bone erosion: The role of sequestosome 1 in Paget's disease of bone.

Alterations in the gene are a putative cause of Paget's disease of bone, yet results are conflicting about how these mutations impact osteoclasts, the cell type believed to be the main pathological c...

Paget's disease of the lumbar spine: decompressive surgery following 17 years of bisphosphonate treatment.

We present a rare case of Paget's disease (PD) with involvement of the lumbar spine over a period of 19 years. We discuss the diagnostic process to rule out alternative diagnoses and medical and surg...

Paget's disease of bone: diagnosis and treatment..

Paget's disease of bone is a common bone disorder characterized by disorganized bone remodeling. The most likely etiology is a slow paramyxoviral viral infection in genetically susceptible individuals...

"Extramammary-Type" Paget Disease of the Breast.

Mammary Paget disease and extramammary Paget disease (EMPD) have different prognoses. Because they are indistinguishable on histopathological grounds, they must be distinguished on a topographical bas...

Clinical utility of bone markers in various diseases.

Measurements of bone markers (BMs) in peripheral blood or urine are a pivotal part of bone research within modern clinical medicine. In recent years the use of BMs increased substantially as they can ...

Medical and Biotech [MESH] Definitions

Necrotic jaws or other maxillofacial skeleton necrosis associated with bisphosphonate use (see BISPHOSPHONATES). Injury, dental procedures, and trauma can trigger the necrotic process.

An intraductal carcinoma of the breast extending to involve the nipple and areola, characterized clinically by eczema-like inflammatory skin changes and histologically by infiltration of the dermis by malignant cells (Paget's cells). (Dorland, 27th ed)


Decalcification of bone or abnormal bone development due to chronic KIDNEY DISEASES, in which 1,25-DIHYDROXYVITAMIN D3 synthesis by the kidneys is impaired, leading to reduced negative feedback on PARATHYROID HORMONE. The resulting SECONDARY HYPERPARATHYROIDISM eventually leads to bone disorders.

A disease of bone marked by thinning of the cortex and replacement of bone marrow by gritty fibrous tissue containing bony spicules, producing pain, disability, and gradually increasing deformity. Only one bone may be involved (FIBROUS DYSPLASIA, MONOSTOTIC) or several (FIBROUS DYSPLASIA, POLYOSTOTIC). (From Dorland, 28th ed)

More From BioPortfolio on "18F-Fluoride Positron Emission Tomography (PET) in Paget's Disease of Bone"

Quick Search


Relevant Topics

Biological Therapy
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...

Osteoporosis is a disease in which the bones become extremely porous, are subject to fracture, and heal slowly, occurring especially in women following menopause and often leading to curvature of the spine from vertebral collapse. Follow and track&n...

Searches Linking to this Trial