1. Radiopharmaceuticals for bone imaging - there are many phosphorus type compounds that have been developed over the years, however, for now we will only discuss the ones that are most important
1. ^99mTcPyrophosphate (PYP)
   1. This agent is really not used as a bone agent because MDP has improved target to background when compared to PYP
   2. PYP is mostly used for cardiac imaging because of its high Tin (Sn) level. Sn reduces ^99mTcO₄^- allowing pertechnetate to tag to the RBC thus allowing the ability to image the vascular pool (GI bleeds and gated cardiacs)


1 - http://www.med.harvard.edu/JPNM/InterestingImages/Case18ii/Dx18.html
2 - http://www.brighamandwomens.org/departments_and_services/radiology/services/nuclearmedicine/patient/bone.aspx

2. ^99mTc Methylene diphosphonate (^9mTcMDP) is the agent most routinely used agent to image the skeletal system
   1. It has greater target to background
   2. Consider target to background in the above images. What comments might you have?
   3. Why do you think there is such a difference between the two?
   
   
2. Physiology of the radiopharmaceuticals
1. Must consider vascularity and bone production/turnover
2. Uptake is based on radiotracer exchange with ions in the bony matrix known as heterionic exchange. This is also referred to as chemisorption
3. Calcium is located on the hydroxyapatite crystal (bony matrix)
4. Phosphate compounds exchange with Ca on the hydroxyapatite crystal
5. Osteoclasts and osteoblasts work on the bony matrix
1. Uptake of the radiotracers increases when there is high metabolic activity
2. Usually this activity, in adults, is due to excessive bone destruction (bone turnover) - blastic vs lytic
6. Normal distribution of radiopharmaceutical
1. Up to 50 percent of the injected bone agent will be eliminated through the kidneys within 3 hours
2. Fifty to 60 percent of the radiotracer will localize in bone
3. Concentration of the radiotracer is greater in the central skeleton and less in the peripheral bone (chest vs. hands/feet)
1. Consider vascular flow and relate this to tracer distribution
2. Consider imaging central skeleton vs. peripheral bone and how it might affect acquisition? Where would the count rate be greater?


3. Some technical considerations must be applied when acquiring data - see "What's in a scan"
1. Detector size
1. Increasing the size of the detector means increasing its field of view (FOV). In turn, the larger the FOV the greater amount of counts are needed to get the same resolution
2. As an example, a 15-inch detector may require a 500k image of the chest, however, a 21 inch detector would require a 1,000k image in order to achieve the same count density



2. Bladder activity may obscure lesions located within the pelvis - remember 50% is excreted out the kidneys


http://www.slideshare.net/lahollenbeck/the-bone-scan

3. Urine on the clothing or skin may create a lesion artifact within the bone and/or soft tissue hot spots were discovered in the above scan. The patient was asked to wash her leg then re-imaged. Has the image changed?
4. Hydration improves the quality of the scan by increasing urine production and therefore eliminating more radiotracer from the soft tissue. This improves target to background
5. The body is bilaterally symmetrical; hence, asymmetry in a bone scan may indicate disease


http://www.wjnm.org/article.asp?issn=1450-1147;year=2014;volume=13;issue=2;spage=132;epage=134;aulast=Marzooq

6. If urinary tract obstruction is suspected, ambulate the patient, have the patient void, and re-image. This patient has a recto-sigmoid tumor pressing against the left ureter
7. ^99mTc to is very sensitive to O₂. It breaks down the Tc - MDP tag
8. Images are taken in several different formats
   1. Dynamic (flow) study
   2. Immediate and delayed static images (delays usually occur 2-3 hours post-injection)
   3. Whole body or static images are taken on delays
   4. Single Emission Computerized Tomography (SPECT) will be discussed later

Types of Bone Scans

4. Three Phase Bone Scan - usually has three portions to the exam
1. Dynamic (flow)
2. Pooling (early or immediate)
3. Delays (3 hours)

5. Whole body bone scan
1. Requires a large field of view camera
2. The detector will image the entire body (top of head to the end of the feet)
3. Usually acquire a scan speed around 12 cm/minutes (or less).
   1. This indicates the speed in which the table or detector moves across the patient
   2. Slower speeds will give greater counts and will improve count density
4. Most systems have dual heads which is more efficient than a single head because you acquire both anterior and posterior images at the same time
5. Whole body contouring further improves resolution
6. Increasing distance (patient to detector) significantly reduces resolution and increases scatter counts
7. Don't forget the urinary bladder. Too much activity in that area will cause a loss of bone detail. This is a concern, especially if there is disease in the pelvic region. Have the patient empty his/her bladder before re-acquiring the data


6. Spot views or limited bone scan
1. Most bone scans image the entire body, however, sometimes a limited bone scan is ordered. This requires data to be collected only in a specific area within the skeletal system
2. Feet, hands, wrists and elbows are examples of when a spot view might be ordered
3. A limited bone scan may or may not include a three-phase bone scan


https://www.mussenhealth.us/intense-tracer/introduction-and-fundamentals-of-pinhole-scintigraphy.html



7. Pinhole image of the bone
1. Pinhole collimator may be used to magnify specific areas of interest (head of the femur, patella, and/or bones in the feet or hands
2. In order to acquire this high resolution image, remember that the acquisition will take a long time - Why?
   1. Consider the inverse relationship between resolution and sensitivity
   2. Remember an image must have enough counts to resolve the magnified area of interest




https://www.slideshare.net/sitanshubarik/bone-scan-32264871/28

8. SPECT Bone
1. Should be used when bone disease involves overlapping bone (ex. spine or mandible)
2. A whole body bone scan may look normal in the spine and show a hot spot within a vertebral body when SPECT is used

1. General
1. Skeletal system is bilaterally symmetrical - results of disease will show increased uptake of radiotracer on the affected side, while normal accumulation will occur on the unaffected sided
2. Clearance of the radiotracer from blood pool/soft tissue improves target to background over time. Hence delayed imaging is very important
3. Bone scans are sensitive in finding disease in the bone (>90%). The problem is - what caused the hot spot? Fracture, infection, or mets?
2. Osteomyelitis - infection involving the bone
1. Requires a three phase bone scan
2. Dynamic phase show increased blood flow the effective site
3. Immediate static shows increased activity that becomes more focal
4. Three-hour delays show increased uptake that is usually focal
Two Second Flow Study (First part of a 3-phase)

This patient was suspected of having osteomyelitis to his left knee. Increased blood flow and uptake is noted on the flow study indicating the classical pattern seen when this disease is present.

Immediate - Phase 2

Delay - Phase 3

The image on the left is the immediate static image, showing significantly increased uptake on the affected side. The right image is a 3-hour delay, indicating that the left knee has greater uptake when compared to the right. In pediactric patients the knees always look hotter. This is because these patients have active bone growth

3. Metastatic disease - cancer that spreads to the bone
1. Primary cancer may metastasize to bone tissue
2. Metastatic disease is usually seen axial skeleton and to a lesser degree in the appendages
3. A bone scan can help in initial staging and/or analyze how the disease is progressing over time
4. There may be only one, two, or many lesions [hot(s)]


This patient has metastatic carcinoma, which originated in the prostate. Notice the numerous sites of increased uptake. This shows extensive carcinoma involvement though out the skeletal system

4. Padget's disease
1. Benign tumors
2. High bone turnover rate
3. Pelvis with femur involvement and/or skull


Padget's disease has invaded the pelvis and both hips. In addition, disease can be noted in the skull.

5. Arthritis
1. Effects articulations (joints) - shows increased activity
2. Joint scan includes imaging all articulating processes


While arthritis can invade any articulating process in the body, this image is a good example of arthritis in the phalanges and wrist.


6. Fractures
1. Within 24 hours and as long as 72 hours a fracture will appear hot on a bone scan
2. Fractures appear hot because the bone is repairing itself
3. Old fractures (up to 2 years) may still show increased uptake (about 10%)
4. The images above is an exam of a stress fracture

As stated earlier, diseases in the bone may show similar patterns (bone scans are sensitive to finding disease but not always specific to the type of disease. The above skull view looks somewhat like Padget's disease, but in reality the disease that is present is metastatic carcinoma