18F-NaF PET Imaging for Bone Scintigraphy

Study Overview
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Brief Summary
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The purpose of this study is to compare, in patients with prostate or breast cancer, the accuracy of 18F-NaF PET imaging to 99mTc whole body bone scans with single-photon emission computed tomography (SPECT).

Detailed Description
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Technetium-99m (99mTc) is the most widely used radionuclide in diagnostic nuclear medicine studies. It is used in 20 million diagnostic procedures worldwide annually. It became popular as a radioisotope because of its easy availability from a 99Molybdenum (99Mo)/99mTc generator, historic low costs, and previous high availability. The National Research Universal (NRU) reactor at Chalk River Laboratories (Ontario, Canada) was shut down unexpectedly in May 2009 following a leak of heavy water. The NRU reactor supplied approximately a third of the world's demand of 99Mo for 99Mo/99mTc generators used diagnostic nuclear medicine tests. Given the fragility of 99Mo supply, alternative radiopharmaceuticals, such as 18F-Sodium Fluoride (18F-NaF), are attractive options to replace 99mTc bone scans. Several studies suggest that 18F-NaF may be more accurate and more sensitive in the detection of bone metastases than 99mTc bone scans.

Official Title
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18F- Sodium Fluoride PET Imaging as a Replacement for Bone Scintigraphy

Conditions
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Bone Metastases From Breast or Prostate Cancer

Intervention / Treatment
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* Procedure: NaF PET/CT Imaging
* Procedure: 99mTc-medronate whole body bone scan with SPECT
* Drug: 18F-Sodium Fluoride (NaF)


Participation Criteria
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Eligibility Criteria
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All Subject Inclusion Criteria All subjects must have a WHO performance status 0-2. Subjects ≥ 18/19 years of age (depending on the age of majority in the province where the trial is conducted) For Prostate Cancer: Male subjects requiring a bone scan for evaluation of bone metastasis with one (or more) of the following criteria: Symptomatic subjects with clinically suspected bone metastases based on a history of non-joint skeletal pain or non-joint skeletal tenderness on physical examination. The physician must have a high index of suspicion based on history or physical examination, such as night time pain or new onset of pain unexplained by trauma. Such subjects must have a measurable PSA level ≥ 4 ng/mL. Subjects with findings on other examinations (such as plain x-ray, CT, MRI or bone scintigraphy and others) that are suspicious for bone metastases but not conclusively diagnostic of bone metastases. Asymptomatic subjects with newly diagnosed localized prostate cancer[1] and biopsy Gleason sum 8 -10 (e.g. scores 3+5, 5+3, 4+4, 4+5, 5+4 or 5+5) prior to treatment. Asymptomatic subjects with newly diagnosed localized prostate cancer[1] and biopsy Gleason score (4+3) and either PSA level ≥ 20 or palpable disease (cT2b or greater) prior to treatment. Asymptomatic subjects with newly diagnosed localized prostate cancer[1] with PSA level ≥ 20 and palpable disease (any cT2 or greater) prior to treatment. Asymptomatic subjects with a prior history of treated prostate cancer, and rising PSA, with a PSA doubling time < 6 months, and a minimum PSA level ≥ 4 ng/mL Asymptomatic subjects with a prior history of treated prostate cancer, and rising PSA while under androgen deprivation therapy, with a clearly measurable PSA doubling time < 6 months (treatment does not need to be discontinued for eligibility). Notes: [1] Subjects with newly diagnosed prostate cancer who receive androgen deprivation therapy, for a duration of < 6 months at the time of enrolment, prior to radiation therapy or surgery, remain eligible to participate in this study if they meet these inclusion criteria. For Breast Cancer: Subjects (male or female) requiring a bone scan for evaluation of bone metastasis with one (or more) of the following criteria (19-23): Symptomatic subjects with clinically suspected bone metastases based on a history of non-joint skeletal pain or non-joint skeletal tenderness on physical examination. The physician must have a high index of suspicion based on history or physical examination, such as night time pain or new onset of pain unexplained by trauma. Subjects with findings on other examinations (such as plain x-ray, CT, MRI or bone scintigraphy and others) that are suspicious for bone metastases but not conclusively diagnostic of bone metastases. Asymptomatic subjects with newly diagnosed extra-skeletal metastatic breast cancer (stage IV). Asymptomatic subjects with elevated serum cancer antigen (CA) 15.3 or alkaline phosphatase and newly diagnosed locally advanced breast cancer (Stage III). Asymptomatic subjects with nodal or extra-skeletal metastatic relapse during follow-up after curative-intent therapy. Asymptomatic subjects with new elevation of CA 15.3 or alkaline phosphatase during follow-up after curative-intent therapy. Subject Exclusion Criteria Pregnancy. Inability to lie supine for the duration of the imaging studies. Subjects previously known for bone metastasis diagnosed by imaging or biopsy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 18F-NaF PET Imaging for Bone Scintigraphy<br>All participants will receive PET/CT Imaging using the investigational drug 18F-NaF and a 99mTc-medronate whole body bone scan with SPECT to compare the diagnostic ability of the two methods for the presence of bone metastases. | Procedure: NaF PET/CT Imaging<br>* Diagnostic imaging test that is considered investigational<br>Procedure: 99mTc-medronate whole body bone scan with SPECT<br>* 99mTc-medronate whole body bone scan with SPECT imaging. Note, that this is a standard procedure in this patient population and thus is not considered investigational.<br>Drug: 18F-Sodium Fluoride (NaF)<br>* A single radioactive dose of 18F-NaF (185-370 MBq) is intravenously administered to subject 60 minutes prior to PET/CT imaging to evaluate whether or not subject has bone metastasis from advanced prostate or breast cancer. Entire procedure from injection to scan completion will take about 2.25 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy, sensitivity, and specificity of 18F-Sodium Fluoride (18F-NaF) Positron Emission Tomography compared to 99mTc-Methylene Diphosphonate (MDP) bone SPECT imaging for detection of bone metastasis. | To compare the accuracy, sensitivity, and specificity of 18F-NaF imaging and 99mTc-MDP bone SPECT imaging for bone metastasis detection in patients with breast and prostate cancer. | At the 24 month post PET/CT follow-up physical examination. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary outcome is to monitor the short-term side-effects following 18F-NaF PET/CT to assess for adverse drug reactions | Given that 18F-NaF is the investigational agent in this study, the collection of adverse events will focus on identifying potential events related to the administration of this radiopharmaceutical. Adverse events will also be collected for bone scanning with 99mTc-medronate. | Short-term side effects will be monitored for 24 hours following the injection of 18F-NaF (investigational product), and 72 hours following administration of 99mTc-MDP (standard treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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18F-NaF PET/CT, Bone imaging