Changing of the Guard

Changing of the Guard

(The Sodium Fluoride Bone Scan)By Karen WikiSponsored by Cyclotek

Thank you for the introduction and the opportunity to speak today on F18 Sodium fluoride bone scans.

1What is 18F-Sodium Fluoride (NaF)Half Life = 109minsEnergy = 511 keVHighly sensitive bone seeking tracerUptake mechanism resembles 99mTc MDPExcellent pharmacokinetic characteristics

So the big question is, what is 18F Sodium Fluoride or NaF ? Well its a positron emitting radiopharmaceutical that is produced in a cyclotron, It has a half life of 109 minutes and an energy of 511keV.NaF is a highly sensitive bone seeking tracer. NaFs uptake mechanism resembles that of Tc99m MDP (MDP is one of the agents which can be used for a traditional Nuclear Medicine Bone scan). However NaF has better pharmacokinetic characteristics.

So before your eyes start glazing over. A NaF Bone scan is basically the BMW compared to the Toyota when you think of a Nuclear Medicine Bone Scan.

2History

Recognised in the late 60s Early 70s 18F as an excellent tracer for skeletal imaging

Limitations = short half life, high energy level, poor scanner design and availability

NaF was discovered in the late 60s early 70s and recognised as an excellent tracer for skeletal imaging.However at this time it had several limitations, Such as its high energy, inadequate scanner design, short half life and a big factor was poor availability to Cyclotrons that could actually produce the agent. 3

With wide spread availability of Moly generators, which is what we use every day in our Nuclear Medicine departments. Tc99m bone labelled tracers were developed and scanner technologyImproved in imaging these agents. The NaF Bone scan seemed to meet its day. 499mTc Bone Scan

The diagnostic accuracy of Tc99m Bone Scans has improved over time with the improvement of gamma cameras and the introduction of SPECT and even further so with Hybrid SPECT/CT systems as seen here.5PET/CT

18F NaF

As time has moved on we have seen the development of PET scanners and the introduction of modern PET/CT systems. With this development in PET/CT hybrid technology we are now starting to see NaF bone scans come back into favour.

Having a NaF Bone scan means that the patient can have both their bone scan and CT scan performed at the same time. This also improves specificity, sensitivity and accuracy of the scan.

The question may be asked why do a PET and CT scan. Well this comes down to the technology and physics which I have no intention of boring you with. Basically on any PET scan we perform we require a CT scan to apply an attenuation correction Map to the PET data. Therefore you could acquire a very low dose poor quality CT just for attenuation of PET data, or we can acquire various degrees of CT quality depending on what the clinical question is being asked.

For the Oncology patient this means the patient can have a Full Diagnostic CT with IV contrast followed by the PET Bone Scan.6

So what is the major factor that has given us the ability to perform a NaF Bone scan at Pacific Radiology. Well its the forward thinking of Pacific Radiology and Cyclotek Pharmaceuticals. Thanks to Cyclotek Pharmaceuticals, Pacific Radiology started sourcing NaF from Cycloteks Melbourne Branch in June 2011. The flight would hopefully arrive around 3pm and then an evening session of around 8 patients would start. Cyclotek Pharmaceuticals built a Cyclotron in Wellington in 2011, in January 2012 the Wellington Cyclotek started producing NaF routinely on a Thursday for New Zealand. The installation of this cyclotron has meant Cyclotek Pharmaceuticals has been producing 2 PET agents for clients New Zealand wide. Which means as a country we have gone from one PET/CT scanner at Pacific Radiology to 5 PET/CT systems now operating New Zealand wide. This has been a huge development for Functional PET/CT imaging in New Zealand.

718F NaF

99mTc BS

Both of these scans were obtained on patients in the 60-65 yr old age bracket. As you can see NaF scan is a lot more detailed. We dont get any protein binding seen here in the soft tissues on the Nuclear Medicine Bone scan on the left.

Another big difference is that when you injection Tc99m MDP you only get 35-50% of the injection taken up by the bone. With NaF we see at least 50% of the dose Taken up on the bone structure. NaFAnd the difference in the Bone uptake between the two.

8ImagingHDPNaFRadioisotopeHalf Life6hrs109minsDose740-900 MBq150-250 MBqPrepHydrationHydrationUptake delay2-4hrs45-60mins

Scan duration60 min (WB+SPECT/CT)30 min(L Spine SPECT/CT)25 min (WB contrast)10 min (L Spine)

The patient must be well hydrated for both techniques. With MDP you give an injection and then wait 2-4 hours before imaging however with NaF you only have to wait 45 mins following injection before you can start imaging. And in our department scan duration is halved using NaF.This means you can effectively double to triple your daily work load using NaF, Oncology patients who would have previously had a diagnostic CT chest/abdo/pelvis and then a BS with probable SPECT/CT now get to have one examination in the space of 1 hrs as apposed to a CT that take 30min followed by bone inj, leaving the department for 2-3 hrs and returning for a 45 to 60 min scan. After speaking to patients who have had the test done both was they find the NaF scan less stressful and less invasive on their time.

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64 SLICE

GE Discovery VCT 64 sliceGE Infinia Hawkeye SPECT/CT

The accuracy, sensitivity and specificity of a bone scan is improved by fusion with CT images. At Pacific Radiology we have a GE Infinia Hawyke eye with 4 slice CT and a GE Discovery VCT 64 slice. Our 4 slice has a fixed mA and kV where with the 64 slice we have complete manipulation of acquisition, reconstruction and reformat factors.

10Combined Total Bone Scan Referrals

So lets get down to the impact it has had on our practice at Pacific Radiology. We started started sourcing NaF from Cycloteks Melbourne branch in June 2011 and the Wellington branch started producing in Jan 2012. The graphs here represent the total number of Bone Referrals for the past 4 years. With our Nuclear Medicine Tc99mHDPBone in the blue and NaF in the yellow. In 2012 and 2013 55- 60% of the our bone scan are now performed using NaF.11Oncology Referrers

Over all our Oncology referrers a trendy towards a preference of NaF. Those HDP scans performed were generally urgent scans that couldnt wait for the next NaF session or they are scans that have insurance funding issues. Thus their insurance covers them for a Traditional Nuclear Medicine Bone scan but it will not cover a NaF scan. Some of you may be think well it must be due to cost. The fact is the Naf Bone scan costs exactly the same as a Tc99m whole-body bone scan with SPECT/CT.12 Ca Breast

If we break these graphs down further to look just at Ca Breast patients. Over half of the Bone scans we perform now use NaF.And again those performed as a Tc labelled bone scan are due to urgency or funding issues.13Case Study 1

Its all very well me saying NaF is more favourible but what doses this actually mean? The first case study Id like to present is on a 56 year old female who presented in 2012 to Wellington Hospital with Metastatic Breast cancer and Bony Mets. She had previously had a L mastectomy and at this stage no prior imaging was available at the time of reporting.

CT Chest/Abdo/Pelvis was performed in August 2012. Showing diffuse axial and appendicular lytic and sclerotic foci14

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A Nuclear Medicine Bone scan was performed in September 2012 at Wellington HospitalShowing Increased uptake in T*,10 and 11. Prominent uptake in the right humeral head.Increased uptake in the Left ASIS and Right IschiumNo abnormalities are seen in the skull, chest wall, or lower limbs.

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Patient had increasing bony pain and a repeat CT scan performed in May 2013.Again Multiple bony mets noted with no significant interval change from previous imaging.17

Again showing Multiple boney mets with no significant interval change from previous imaging.

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In May 2013 a another Bone scan was performed at Pacific Radiologiys Nuclear Medicine Department, due to the patients increasing bone pain .The conclusion was made that the appearance on the Nuclear Medicine Bone scan seemed to have improved despite the clinical concern.The recommendation was made for a more sensitive imaging technique, such as a NaF PET/CT bone scan or MRI of the spine.

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So in March 2014 the patient had a Sodium Fluoride Bone scan.We can clearly see multiple foci of abnormal NaF tracer activity throughout The skeleton consistent with extensive osseous metastatic disease seen on the priorCT scans.20

This is an example of the fused images we obtain, CT, PET, Fused and MIP21Case Study 2

99mTc BS

Case study 2.Patient presented with Ca Breast for Staging in 2008. Appearances on this bone were normal with no bony metastatic disease seen.

2218F NaF

She represented in 2012 for Restaging due to right supraclavicular lymphadenopathy, and cough with bilateral pleuric pain.A NaF scan with full diagnostic CT with IV contrast was performed.The NaF scan showed multiple bone lesions and degenerative changes.2318F NaF

She represented in 2012 for Restaging due to right supraclavicular lymphadenopathy, and cough with bilateral pleuric pain.A NaF scan with full diagnostic CT with IV contrast was performed.The NaF scan showed multiple bone lesions and degenerative changes.24

Mixed sclerotic and lytic lesions25

Lytic lesion in Left inferior scapular. We actually get to see lytic lesions with NaF, where depending on the phase we struggle to detect these sometimesWith a Nuclear Medicine Bone Scan.26

This is patient also had two Brain Mets one of which seen herer on the CT images27

There was also a mass in the posterior aspect of the right lung in the lower lobe with some central cavitation. There was bilateral supraclavicular lymphadenopathy, and extensive mediastinum and right hilar lymphadenopathy. The pattern of metastatic disease is not clearly all uniform for metastatic Ca Breast, in particular the lung lesion as shown. And primary lung cancer was suggested with confirmation required via an FNA

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I actually questioned this Lady on her experience with NaF and being able to have her Diagnostic CT scan performed at the same time.She said it was far easier just getting everything over and done with and it didnt take as much time to complete, when compaired to her previous appointments of a seperate Nuclear Medicine Bone scan and separate CT Chest/Abdo/ Pelvis.

29Advantages of NaF PET/CTSuperior pharmacokineticsSensitive for lytic lesionsBetter resolution and sensitivityRoutine tomographic dataRoutine use of CT improves specificityShorter total examination timeOne stop shop

Due to its quicker uptake and imaging times, increased sensitivity and better image quality. The majority of ourReferrers prefer NaF and we are seeing its impact in our practice.

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In finishing, I think the NaF PET/CT is the bone scan of the future as it provides Functional PET data and Diagnostic CT data, improving the accuracy, specificity and sensitivity of the examination.Id like to give a big thank you to Cyclotek PET Radiopharmaceuticals with providing us with this radiopharmaceutical and especially for their sponsorshipIn helping me present at this meeting. 31ReferencesThe SNM Practice Guideline For Sodium 18F-Fluoride PET/CT Bone Scans 1.1Grant FD, Fahey FH, Packard AB, Davis RT, Alvai A, and Treves ST. Skeletal PET with 18-Fluoride: Applying New Technology to an Old Tracer. JNM 2008;49:68-78.Apostolova I, Brenner W. Measuring Bone Metabolism with Fluoride PET: Methodological Considerations. PET Clin 2010;5:247-257.Abikhzer G, Kennedy J. 18F NaF PET/CT and conventional Bone Scanning in Routine Clinical Practice; Compartive Analysis of Tracers, Clinical Acquisition Protocols, and Performance Indices. PET Clin 2012;:315-328.Czernin J, Satyamurthy N, Schiepers C. Molecular Mechanisms of Bone 18F-NaF Deposition. JNM 2010;51:1826-1829Klaus Strodel, Reza Vali. 18F NaF PET/CT Versus Conventional Bone Scanning in the Assessment of Benign Bone Disease. PET Clin 2012Mosci C, Lagaru A. 18F NaF PET/CT in the Assessment of Malignant Bone Disease. PET Clin 2012Southern Cross Health Insurance Eligibility criteria PET/CT

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33Breast CancerInitial Staging in high risk Breast Cancer(Clinical Stage lllA or higher) orInitial Staging in Clinical l-llB Breast Cancer with symptoms of bone pain or elevated alkaline phosphatase levels suggesting the presence of bone metastasesRestaging of all stage disease with symptoms of bone pain or elevated alkaline phosphatase levels strongly suggestive of the presence of bone metastases Southern Cross Health Insurance

So what are the Funding issues when it comes to NaF when we consider the Breast Cancer Patient. The only Insurance policy that I could find the Stipulates NaF was Southern Cross.34Comparison of pharmacokinetic properties MDPNaFFirst-pass clearance~ 64%Nearly 100%Protein binding50% at 4 hrNegligible% Bone uptake35%-50%50%Urinary excretion70% after 6 hr50% after 6 hrPET 2012Clin 7 () 315-328

Earlier I mentioned the favourable pharmacokinetic properties of NaF. So lets have a closer look.One of the most important thing to take away from this slide is the Negligible protein binding of the NaFAnd the % Bone uptake difference between the MDP and the NaF.

35Dose Comparison Chart99mTc Bone Scan with SPECT/CT750MBq (70kg pt)Low Dose CT= 2.5 mSv= 2 mSvTotal = 4.5 mSv18F NaF Lumbar Spine200 MBq (70kg pt)Low Dose CT= 4.5 mSv= 3 mSvTotal = 7.5 mSv18F NaF WB withDiagnostic CT200 MBq (70kg pt)Diagnostic CT= 4.5 mSv= 13 mSvTotal = 17.5 mSvBy Dr Alex Mitchell QHP

You may ask what is the radiation dose difference. Well we can see here that the radiation exposure is slightly higher when using NaF. However when we consider that a good portion of the patients we see would have previously had a Diagnostic CT and then an HDp Bone scan for diagnosis. It all evens out to the same as the NaF PET/CT36CT ParametersScanTypeThickSpeed

DFOVkVmA

ReconTypeFull DiagnosticCT with ChestHelicalFull0.5s3.75

0.984:170120AutoMax 600Min 150Bone+WBLow Dose CTHelicalFull0.5s3.75

0.984:1

70120AutoMax 110Min 40Bone+The great thing about NaF is that because its a PET/CT scan we can perform the CT component several ways. We can either perform it with a Low dose CT scan, in which the images are still good enough for interpretation but they are not what you would regard as true CT diagnostic quality. Or we can perform it a Full Diagnostic CT. In these cases the patients would have a non contrast breath hold CT Chest, Followed by a Diagnostic CT with IV contrast. 37 Limitations of 99mTc Bone ScanInferior spatial resolution and sensitivity of gamma camerasLonger uptake timeLonger scan timesSPECT/CT isnt routinely used

So in summary38Advantages of 99mTc Bone ScanWide availabilityGenerator produced/daily elutionLonger physical half-lifeFlow, blood pool and delayedLower radiation dose (0.0057mSv/MBq)

39Limitations of NaF PET/CTCyclotron producedAvailabilityHigher radiation exposureLack of flow and blood pool capabilities

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