1. SKELETAL RADIONUCLIDE IMAGING II
Dr. Hussein Farghaly
Nuclear Medicine Consultant
PSMMC

2. CONTENTS Bone and BM physiology & anatomy Bone scan Bone Marrow scan
Radiopharmaceutical,
preparation,
uptake and pharmacokinetics
dosimetry,
protocols,
normal and altered distribution
Clinical indication and Skeletal pathology
Bone Marrow scan

3. Bone scan Radiopharmaceutical
Preparation
uptake and pharmacokinetics
dosimetry
protocols
normal and altered distribution

4. Radiopharmaceutical
Therefore a radiopharmaceutical is typically made of two components, the radionuclide and the chemical compound to which it is bound.
Since radiopharmaceuticals are used to study body functions, it is important that they have no pharmacological or toxicological effects which may interfere with the organ function under study. Therefore the pharmaceutical is administered in extremely small amounts (10-9 g).
An ideal radiopharmaceutical for skeletal scintigraphy must be inexpensive, remain stable, rapidly localize to bone, quickly clear from the background soft tissues, and have favorable imaging and dosimetry characteristics.
These parameters were essentially met in the 1970s when technetium-99m,already desirable for gamma camera imaging studies, was combined with members of the phosphate family.

5. History of Bone Radiotracer
Radium-226, 1920
Phosphorus-32, radioisotopes of calcium, several rare earth elements, and isotopes of gallium, barium, samarium, and strontium.
(F-18) is an analog of the hydroxyl ion found in calcium hydroxyapatite and avidly localizes to bone. It was the agent of choice for skeletal scintigraphy until the advent of the :
Tc-99m phosphonates in the 1970s.

6. Other substances that can be used but I will only mention in passing are:
gallium,
thallium,
indium & Tc-99m labeled leucocytes
and polyclonal immunoglobulins labeled with technetium.

7. Technetium-99m phosphate family
These radiopharmaceuticals are classified by the type of phosphate bond. The first of these agents, pyrophosphates and then the longer-chain polyphosphates, were
soon replaced by the diphosphonates .
The diphosphonates are more stable in the body and have better background clearance than pyrophosphates or polyphosphates.
The diphosphonate agents include Tc-99m hydroxyethylidene diphosphonate (Tc-99m HEDP),Tc-99m hydroxymethylene diphosphonate (Tc-99m HMDP or HDP), and Tc-99m methylene diphosphonate (Tc-99m MDP).
The ability of each diphosphonate to detect lesions has been studied. Although some differences are present,Tc-99m MDP and Tc-99m HDP are both excellent agents.

8. PREPARARTION

9. Radiopharmaceutical quality control:
Visual Inspection of Product
Visual inspection of the compounded radiopharmaceutical shall be conducted to ensure the absence of foreign matter and also to establish product identity by confirming that
a liquid product is a solution, a colloid, or a suspension
a solid product has defined properties that identify it.
Assessment of Radioactivity
-The amount of radioactivity in each compounded radiopharmaceutical should be verified and documented prior to dispensing, using a proper standardized radionuclide (dose) calibrator.

10. Radiopharmaceutical quality control:
Radionuclidic Purity
- Radionuclidic purity can be determined with the use of a suitable counting device
-The gamma-ray spectrum, should not be significantly different from that of a standardized solution of the radionuclide.
Radiochemical purity
Radiochemical purity is assessed by a variety of analytical techniques such as:
liquid chromatography paper chromatography
- thin-layer chromatography electrophoresis
the distribution of radioactivity on the chromatogram is
determined.

11. Radiopharmaceutical quality control:
Labelling
The label on the outer package should include:
a statement that the product is radioactive or the international symbol for radioactivity
the name of the radiopharmaceutical preparation;
the preparation is for diagnostic or for therapeutic use;
the route of administration;
the total radioactivity present (for example, in MBq per ml of the solution)
the expiry date
the batch (lot) number
for solutions, the total volume;
any special storage requirements with respect to temperature and light;
the name and concentration of any added microbial preservative

12. Mechanisms of Localization and Pharmacokinetics
After intravenous injection,Tc-99m MDP rapidly distributes into the extracellular fluid and is quickly taken up into the bone.
Tc-99m MDP accumulates controlled by
primarily in relation to osteogenic activity levels,
amount of blood flow plays a part.
Activity is much higher in areas of active bone formation compared with mature bone.
Tc-99m MDP binding occurs by chemoadsorption in the hydroxyapatite mineral component of the osseous matrix.
Uptake in areas of amorphous calcium phosphate may account for Tc-99m MDP uptake in sites outside the bone, such as dystrophic soft tissue ossification.
At 3 hours, Tc-99m MDP concentration in
normal tissues is proportional to their calcium
content, ranging from a low concentration in
muscle (0.005% calcium) to a high one in
bone (14%-24% calcium)

13. Mechanisms of Localization and Pharmacokinetics
Approximately 50% of the dose is localized to the bone with the remainder excreted by the kidneys.
Although peak bone uptake occurs approximately 1 hour after injection, highest target-to-background ratios are seen after 6–12 hours. This must be balanced with the relatively short 6-hour half-life of Tc-99m and patient convenience. Therefore, images are typically taken 2–4 hours after injection.
Serum radiotracer levels at this time are down to 3–5% of the injected dose in patients with normal renal function.
It should be noted that the half-life of Tc-99m effectively limits imaging to within approximately 24 hours of injection.
Decreased localization is seen in areas of reduced or absent blood flow or infarction. Diminished uptake is also seen in areas of severe destruction that can occur in
some very aggressive metastasis

14. Dosimetry
The radiation dose to the bladder wall, ovaries, and testes depends on the frequency of voiding.
The dosimetry provided assumes a 2-hour voiding cycle.
Significantly higher doses result if voiding is infrequent.
Radiopharmaceuticals are administered to pregnant women only if clearly needed on a risk-versus-benefit basis.
Tc-99m is excreted in breast milk so breastfeeding should be stopped for 24 hours

15. Webster’s rule is generally helpful: [age + 1]/
[age + 7] × adult dose.

16. Normal Bone Scan
1. Areas with normally increased activity include: acromioclavicular joints, sternoclavicular joints, scapular tips, costochondral junctions, sacroiliac joints, lower neck, sternum, renal pelves and bladder
2. Pediatric patients: growth centers and cranial sutures
3. Pitfalls
- Patient rotation
- Urine retained in calyx may overlie lower rib
- Urine contamination
- Belt buckles, earrings, necklaces, and the like frequently create cold defects
- Recent dental procedures
- Radiopharmaceutical problems: breakdown of tag leading to free pertechnetate causes activity in thyroid and GI tract

17. Normal Childe Bone Scan
Figure 2.  Anterior (left) and posterior (right) whole-body bone scintigrams obtained in a child demonstrate normal anatomy. Note the increased activity in the physes of the long bones and in the hematopoietically active facial bones.
  Anterior (left) and posterior (right) whole-body bone scintigrams obtained in a child demonstrate normal anatomy. Note the increased activity in the physes of the long bones and in the hematopoietically active facial bones

18.  (a) Anterior bone scintigram shows discrete focal activity in the left maxilla (arrowhead) due to a dental process and heart-shaped activity in the anterior neck (arrow) representing the thyroid cartilage, both of which are normal variants.
Figure 3a.  (a) Anterior bone scintigram shows discrete focal activity in the left maxilla (arrowhead) due to a dental process and heart-shaped activity in the anterior neck (arrow) representing the thyroid cartilage, both of which are normal variants. (b) Posterior bone scintigram shows focal activity in the right side of the neck (arrow) caused by a cervical osteophyte.  

20.  Myocardial uptake in a patient with long-standing congestive heart failure.
 Extra osseous uptake
Free Tc-99m.
Colonic Activity
A-  Myocardial uptake in a patient with long-standing congestive heart failure. Whole-body scintigram shows myocardial uptake and abdominal ascites.
B-    Extraosseous uptake. Anterior whole-body scintigram demonstrates poor bone detail and intense oral and gastric activity. These findings are caused by the introduction of air into the vial or syringe containing the radiotracer, which results in oxidation of the compound and the liberation of free pertechnetate.
C-Extraosseous uptake. Anterior whole-body scintigram demonstrates colonic activity due to previous myocardial perfusion imaging with Tc-99m sestamibi.

21. Artifact from an implanted defibrillator
Artifact from an implanted defibrillator. (a) Planar scintigram shows an apparent photopenic defect in the lower lumbar spine (arrow). (b) Coronal SPECT image does not demonstrate any bone abnormality. (c) Scout CT scan reveals that the cause of the defect is an implanted defibrillator. (d) Transaxial CT scan shows the defibrillator in the left anterior abdominal wall (arrow). .
Planner SPECT- coronal

23. Diffuse hepatic metastasis
Planar images from a whole-body scan with Tc-99m MDP demonstrate
marked hepatomegaly with diffuse hepatic uptake of Tc-99m MDP mimicking
liver-spleen imaging. Decreased bone uptake of Tc-99m MDP is seen.
There is no sign of skeletal metastases.
Gd-DTPA enhanced MR imaging of the abdomen showed innumerable
masses in the liver consistent with hepatic metastases.
Iron Therapy and overload