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

March 20, 2006 updated by: Université Catholique de Louvain

Use of 18F-Fluoride Positron Emission Tomography in the Assessment and Evaluation of Therapy in Monostotic Paget's Disease of Bone

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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 Type

Interventional

Enrollment

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium, 1200
        • Rheumatology, Molecular Imaging and Experimental Radiotherapy departments, Saint-Luc University Hospital, Catholic University of Louvain

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 second and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with a monostotic form of PDB (as attested by plain X-rays and 99mTc MDP bone scintigraphy)
  • Bone pain linked to Paget's disease itself

Exclusion Criteria:

  • Bisphosphonate therapy within the year prior to the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Université Catholique de Louvain

Collaborators

Fonds National de la Recherche Scientifique

Investigators

  • Principal Investigator: Adrien T. NZEUSSEU, MD, Université Catholique de Louvain
  • Principal Investigator: Max LONNEUX, MD, PhD, Université Catholique de Louvain
  • Principal Investigator: Johanne INSTALLE, MD, Université Catholique de Louvain
  • Principal Investigator: Anne BOL, PhD, Université Catholique de Louvain
  • Principal Investigator: Geneviève DEPRESSEUX, Université Catholique de Louvain
  • Study Director: Jean-Pierre DEVOGELAER, MD, Université Catholique de Louvain

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2002

Study Completion

March 1, 2006

Study Registration Dates

First Submitted

March 20, 2006

First Submitted That Met QC Criteria

March 20, 2006

First Posted (Estimate)

March 22, 2006

Study Record Updates

Last Update Posted (Estimate)

March 22, 2006

Last Update Submitted That Met QC Criteria

March 20, 2006

Last Verified

March 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3.4528.03 F

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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