Nuclear medicine in orthopaedic conditions

This presentation helps to develop a basic concept in Nuclear Medicine, It also helps to outline the use of Nuclear Medicine in Orthopaedic diagnostics and Orthopaedic therapeutics.

1. Nuclear Medicine in Orthopaedic Conditions 27 th March 2018 Dr. Gokul Kafle Department of Orthopaedics , AIIMS Moderator: Prof. B Chowdhury Co moderator: Dr. Prasanna T Y

2. Objectives Introduce Nuclear Medicine Nuclear medicine to aid in Orthopaedic diagnostics Nuclear medicine in Orthopaedic therapeutics

3. Nuclear Medicine - Introduction Branch of medicine that deals with the use of radioactive substances in research, diagnosis, and treatment . For diagnostic imaging, radiation emitted from radiopharmaceuticals must be detected by external detectors to determine its in vivo distribution. For therapeutic nuclear medicine, some of the emitted radiation must be absorbed by targeted tissues to achieve the desired effect.

4. Radiology Vs Nuclear Medicine

5. Bohr’s Model of an Atom

6. Basics in N uclear M edicine Different types of atoms are called elements. Different types of nuclei are termed nuclides. An element is characterized by its atomic number (Z)—that is, the number of protons in the nucleus. The atomic number specifies the position of the element in the periodic table. A nuclide is characterized by its atomic number and mass number (A)—that is, protons plus neutrons in the nucleus .

7. Nuclides with the same number of protons and different number of neutrons are called isotopes and belong to the same element . Unstable nuclides are called radionuclides. Radionuclides try to become stable by emitting electromagnetic radiation or charged particles during radioactive decay.

8. Radiopharmaceuticals They are referred to as radiotracers because they are given in sub pharmacological doses that “trace” a particular physiological or pathological process in the body . Radionuclide decay should result in gamma emissions of suitable energy. 100-200 keV : ideal for gamma cameras and 511 keV for PET Emission should be sufficient abundance for external detection. It should not contain particulate radiation (e.g. beta emissions).

9. Effective half-life should be long enough for only the intended application. radionuclide should be carrier-free and should have high specific activity. should rapidly and specifically localize to the intended areas and background clearance should be rapid, leading to good target-to-background ratios .

10. Bone scan Bone scintigraphy is a diagnostic study used to evaluate the distribution of active bone formation in the body. MDP can be labeled with 99mTc because of their good localization in the skeleton and rapid clearance from soft tissues. Areas with higher osteoblastic activity will take up more isotope and show up as “hot” areas on scintigraphy.

11. Technetium (Tc 99m ) most widely used nuclide in diagnostic nuclear medicine Exhibits nearly ideal characteristics Short physical half-life of 6.04 hours pure gamma emitter

12. It can be performed as: Limited bone scintigraphy or spot views (planar images of a selected portion of the skeleton) Whole-body bone scintigraphy (planar images of the entire skeleton) SPECT (single photon emission computed tomography- 3D image of a portion of the skeleton) Multiphase bone scintigraphy (immediate and delayed images to study)

13. In Orthopaedic oncology the standard technique of bone scintigraphy is considered to be the whole-body scan. Whole-body bone scintigraphy produces planar images of the skeleton, including anterior and posterior views of the axial and appendicular skeleton. Limited bone scintigraphy or spot views are indicated only where a specific clinical problem detected on whole-body imaging needs to be clarified.

14. Multiphase Bone Scan Multiphase bone scintigraphy usually includes blood flow images, immediate images, and delayed images. First (dynamic) phase reflects the relative amount of blood flow to the area of interest includes a dynamic sequence of planar images of the area of greatest interest obtained as the tracer is injected .

15. Second (blood pool) phase reflects the amount of activity that has extravagated into the tissues around the area of interest. Includes 1 or more static planar images of the areas of interest, obtained immediately after the flow portion of the study and completed within 10 min.

16. Third (delayed [bone]) phase reflects the rate of bone turnover. Delayed images may be limited to the areas of interest or may include the whole body, may be planar or tomographic, and are usually acquired 2–5 hrs after injection. If necessary, additional delayed images may be obtained up to 24 h after tracer injection .

17. SPECT Scan SPECT is a tomographic examination achieved by rotating the gamma camera 360 o around a patient who has been injected with a radioisotope. SPECT has a higher diagnostic specificity than planar imaging and may be preferable when there is diagnostic uncertainty .

18. Indications of B one Scan Detection and staging of metastatic disease Bone pain in patients with normal radiographs Investigation of abnormal X-ray findings Assessment of possible arthropathy Prosthetic joints for signs of infection or loosening (together with MRI) Differentiation between osteomyelitis and cellulitis

19. Patient recently had contrast media for a different study. Pregnancy (suspected or confirmed): Risk/Benefit Assessment Breast-feeding should be discontinued and milk expressed and discarded when possible for 24 h (and atleast for 4 h) post radiopharmaceutical administration. Contraindications Precautions

20. PATIENT PREPARATION Patient should be well hydrated. Patient should void immediately before study and frequently for next several hours.

21. RADIOPHARMACEUTICAL ADMINISTRATION Injection site should be selected to avoid possible sites of pathology . Adult dose: 20 mCi (740 MBq ), intravenously Pediatric dose: Webster’s rule: Adult dose × [(age + 1)/(age + 7)]. Minimum dose 1.08 mCi (40 MBq)

22. Interpretation of Bone Scan Both increase and decrease in tracer uptake have to be assessed; abnormalities can be either focal or diffuse. Increased/decreased tracer activity in the bone, compared with that in normal bone, indicates increased/decreased osteoblastic activity. Differential diagnosis can sometimes be based on the configuration of the abnormality or abnormalities and the location and number of abnormalities. Most patterns are non-specific .

23. Normal Bone Scan Tracer uptake is greatest in axial skeleton. Kidneys routinely visualized Skull can appear uneven (variations in calvarial thickness) Sites of persistently increased symmetric uptake are acromial and coracoid processes of the scapulae medial ends of the clavicles sternal angle sacral alae

24. Normal Bone Scan- P eds Growth Center most intense: distal femur-proximal tibia- proximal humerus Costochondral junction s

25. Abnormal Patterns – Bone Scan The presence of multiple, randomly distributed areas of increased uptake of varying size, shape, and intensity is highly suggestive of bone metastases. Radiotracer accumulation in both the vertebral body and pedicles usually indicates metastatic disease. Abnormalities that involve the vertebral body and facets but spare the pedicles are usually benign. Activity that is confined to the vertebral body can be due to tumor, trauma, or infection.

26. Flare Phenomenon seen in patients who are responding to treatment, reflects healing of the bone lesions usually observed within 3 months after initiation of treatment and is often associated radiographically with the sclerotic changes that indicate healing. Continued increase in the number and intensity of lesions beyond 6 months is usually indicative of disease progression

27. Superscan When the metastatic process is diffuse, virtually all of the radiotracer is concentrated in the skeleton, with little or no activity in the soft tissues or urinary tract. The resulting pattern, which is characterized by excellent bone detail, is frequently referred to as a superscan A superscan may also be associated with metabolic bone disease. Unlike in metastatic disease the uptake in metabolic bone disease is more uniform in appearance and extends into the distal appendicular skeleton.

28. Superscan

29. Localized causes of “hot” lesions Metastatic disease Primary malignant bone tumor Osteomyelitis Trauma including stress fractures, non-accidental injury , loose prosthesis Osteoid osteoma Paget’s disease Fibrous dysplasia Arthritis Locally increased blood flow

30. Generalized causes of “hot” lesions Primary hyperparathyroidism Renal osteodystrophy Multiple metastases (prostate, lung, breast) Haematologic disorders

31. Causes of cold lesions Overlying artefact from, e.g. pacemaker, barium, etc . Radiation therapy Local vascular compromise, e.g. infarction, early aseptic necrosis Early osteomyelitis Tumour , e.g. Myeloma, plasmacytoma , breast carcinoma

32. Skeletal Trauma 95 % visualized by day 3, maximum positivity by day 7 (age<65 y) advanced age, debilitation can cause delayed or non-visualization Typically in the assessment of subtle trauma such as stress fractures which are often difficult to identify on plain film, and also in the detection of occult scaphoid fractures

33. Stress Fracture radiograph can be negative typical pattern is oval area of increased uptake with long axis parallel to axis of bone

34. Bone Infarction/AVN Appearance depends on time course Acute phase of vascular compromise : affected part of the bone appears photopenic . After revascularization: Intense radiotracer uptake. When repair is complete, radiotracer uptake may return to baseline levels less sensitive than MRI

35. Legg-Calve- Perthes

36. Osteomyelitis Osteomyelitis vs Cellulitis: three phase bone scan for differentiation of cellulitis vs Osteomyelitis The classic appearance of osteomyelitis on three-phase bone scans consists of focal hyper-perfusion, focal hyperemia, and focally increased bone uptake.

37. Assessment of joint prostheses In the initial post-surgical period, activity is noted around the prosthesis. Decreases rapidly and returns to normal within 12 months around the hip, and 18 months around the knee. Persistent activity around the tip of the prosthesis may be taken as an indication of loosening . More generalised activity can be due to infection around the prosthesis. In case of diagnostic dilemma, white cell scintigraphy would be of help. WBC scan would be positive in the case of Infection.

38. Use in benign, non-neoplastic disease Paget’s disease of bone classically displays marked increased activity in the involved skeleton . Fibrous dysplasia , will be active on bone scintigraphy; therefore the technique may be a useful tool in searching for polyostotic involvement.

39. Bone marrow scintigraphy To identify bone marrow replacement by tumor or locate active sites for biopsy . Can also be used to assess femoral head blood supply. 99mTc-sulphur colloid is used.

40. White blood cell (WBC) imaging involves labelling the patient’s own WBCs with the radioactive tracer . agents used most often for labelling are indium and Tc99m-hexamethyl propylenamineoxime . Labelled WBCs usually accumulate in areas of infection but not in areas of increased bone turnover .

41. Positron Emission Tomography ( PET) Scan produces a 3-D image of functional processes in the body by detecting the radiation emitted predominantly in osteolytic lesions where there is no osteoblasts and hence poor tc99 uptake. The system detects pairs of gamma rays emitted indirectly by positron emitting radionuclide (tracer ) 3-D images of tracer concentration within the body are then constructed by computer analysis.

42. Working Principle Injection of Short lived Radioactive Isotope in body. most commonly used is 18-FDG (18-fluoro-2-deoxyglucose). Wait till tracer gets accumulated in tissues of interests; usually 45mins. Subject is placed in the imaging scanner.

43. Tissue concentration is recorded with time. As isotope decays in body, it releases a positron in body. On interaction with an electron, it produces a pair of photons. PET scanner detect these photons and with the help of a computer creates pictures offering details on both the structure and function of organs and tissues in body .

44. Oncology Most widely used Application of PET Tracer used is FDG-18 . Highly accurate as tumor cells consume lot of glucose and t racer is a glucose analog. Also , tracer is bound in tumor cell once it got there until it decays. Thereby , giving more accurate results.

45. PET/CT

46. PET/CT Can b e combined with CT (or even MRI) blending of imaging function and form by merging the functional imaging of PET and anatomical landmarks of CT More powerful diagnostic information is obtainable

47. Uses Multiple myeloma (staging, prognostication, response evaluation) Locate Primary Pathology site Can detect early bone marrow involvement including spinal metastasis before the appearance of cortical changes in bone scintigraphy

48. Radiosynovectomy Open and arthroscopic synovectomies Vs Radio-synovectomy treatment of recurrent synovitis secondary to inflammatory arthritides or hemophilia . The most commonly used radiopharmaceuticals for intra-articular administration are P-32 chromic phosphate colloid, Y-90 and Dy-165 in the form of particulate Dy-165 FHMA

49. Radiopharmaceuticals Commonly Used in Radiosynovectomy

50. Injected agents are thought to be rapidly phagocytosed by synoviocytes and then distributed within the synovium, primarily at the surface. V asculitis results from the radiation effect, which occludes the microvascular supply to the synovium, and this, in addition to the cytotoxic effect of the radiation, results in ablation of the synovium

51. Pigmented Villonodular Synovitis a combination of debulking surgery with intra-articular injection of Y-90 for extensive diffuse PVNS is regarded as a reliable and highly efficacious method of treatment.

52. Synovitis of Other Origins Synovitis associated with severe osteoarthritis, ankylosing spondylitis, reactive arthritis, undifferentiated spondylo-arthropathy , psoriatic arthritis, PVNS, and recurrent synovitis . a good or excellent improvement of clinical symptoms.

53. Metastatic Bone Pain NSAIDs/ Opioid analgesics / chemotherapy or hormonal therapy Bisphosphonates, which are analogues of pyrophosphate and inhibit osteoclast function , may be useful in reducing bone destruction in lytic metastasis and in diminishing hypercalcemia secondary to bone resorption . Historically, use of P-32 reduced or relieved the pain of osteoblastic metastases but with some hematologic toxicity, even when used as a single injection .

54. Sr-89 and Sm-153 have been developed as palliative treatments for patients with severe bone pain from osseous metastases . Offers a high target-to-non target ratio

55. Toxicities The potential toxicity of radionuclide therapy is almost exclusively hematologic, skin necrosis. Flare phenomenon: a transient increase in bone pain beginning 48 to 72 hours after radiopharmaceutical therapy , usually lasts 2 to 3 days. FP is reported to occur in as many as 60% of treated patients and may be a positive predictor of a therapeutic response.

56. Contraindications - Absolute an oncologic emergency, such as cord compression or impending fracture of a weight-bearing long bone

57. Contraindications – Relative known or suspected allergy to radionuclide material and other phosphonate compounds chronically low platelet counts impending spinal cord compression fractures or unstabilized long-bone fractures compromised renal function, and treatment within 6 weeks immediately before or immediately after myelo -suppressive chemotherapy or radiation therapy .

58. Thank you

59. Q & A Which radionuclide is the most widely used for gamma camera?

60. Technetium-99m

61. Which radionuclide is the most widely used for PET?

62. F - 18

63. R adiopharmaceuticals are desired to emit energy in the form of _______ for therapeutics. Gamma Radiation Beta Particle Alpha particle Anyone of the above

64. R adiopharmaceuticals are desired to emit energy in the form of Beta Particle for therapeutics.