Ignite Creation Date:
2024-05-05 @ 4:43 PM
Last Modification Date:
2024-10-26 @ 9:23 AM
Study NCT ID:
NCT00306046
Status:
COMPLETED
Last Update Posted:
2006-03-22
First Post:
2006-03-20
Brief Title:
18F-Fluoride Positron Emission Tomography PET in Pagets Disease of Bone
Sponsor:
Université Catholique de Louvain
Organization:
Université Catholique de Louvain
Study Overview
Official Title:
Use of 18F-Fluoride Positron Emission Tomography in the Assessment and Evaluation of Therapy in Monostotic Pagets Disease of Bone
Status:
COMPLETED
Status Verified Date:
2006-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 Pagets 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
Detailed Description:
I Background of the subject
Pagets 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 Pagets disease activity
However a monostotic Pagets 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 Pagets 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 Pagets 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 Pagets 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 Pagets 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 125OH2 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 18Opn 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 405x439x30 mm size yielding 63 transverse slices 2425 mm thickness in a 162 cm axial FOV In 2D mode the resolution of the HR scanner is typically 54 mm and 50 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 0027 mSvMbq 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 025 mGyMBq
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 Pagets 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 Pagets disease Metab Bone Dis Relat Res 1984 5 167-170
4 Merrick MV Merrick JM Observations on the natural history of Pagets disease Clin Radiol 1985 36 169-174
5 Vellenga CLJR Pauwels EKJ Bijvoet OLM et al Scintigraphic aspects of the recurrence of treated Pagets disease of bone J Nucl Med 1985 54 273-281
6 A Nzeusseu Toukap M Lonneux J Installe A Bolle G Depresseux JP Devogelaer
International Symposium of the National Association for the Relief of Pagets Disease St Catherines college 17-18 july 2003 Oxford UK
18F-Fluoride Positron Emission Tomography Preliminary assessment of therapy in Pagets Disease of Bone
Pagets 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 Pagets disease activity
However a monostotic Pagets 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 Pagets 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 Pagets 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 Pagets 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 Pagets 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 125OH2 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 18Opn 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 405x439x30 mm size yielding 63 transverse slices 2425 mm thickness in a 162 cm axial FOV In 2D mode the resolution of the HR scanner is typically 54 mm and 50 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 0027 mSvMbq 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 025 mGyMBq
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 Pagets 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 Pagets disease Metab Bone Dis Relat Res 1984 5 167-170
4 Merrick MV Merrick JM Observations on the natural history of Pagets disease Clin Radiol 1985 36 169-174
5 Vellenga CLJR Pauwels EKJ Bijvoet OLM et al Scintigraphic aspects of the recurrence of treated Pagets disease of bone J Nucl Med 1985 54 273-281
6 A Nzeusseu Toukap M Lonneux J Installe A Bolle G Depresseux JP Devogelaer
International Symposium of the National Association for the Relief of Pagets Disease St Catherines college 17-18 july 2003 Oxford UK
18F-Fluoride Positron Emission Tomography Preliminary assessment of therapy in Pagets Disease of Bone
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None