Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00306046 |
| Other study ID # |
3.4528.03 F |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
March 20, 2006 |
| Last updated |
March 20, 2006 |
| Start date |
February 2002 |
| Est. completion date |
March 2006 |
Study information
| Verified date |
March 2006 |
| Source |
Université Catholique de Louvain |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Belgium: Institutional Review Board |
| Study type |
Interventional
|
Clinical Trial Summary
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.
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.
