1. Radionuclide imaging in patients with fever Otto Lang MD Dept Nucl Med 3rd School of Medicine Charles University Prague materials for medical students

2. Fever Non-specific reaction of the body (T>38 o C) Most frequent cause inflammation (tumors) Inflammation –Infective and non-infective Usually fever with other signs of imflammation Clinical picture very important Other laboratory tests including imaging methods (NM, sono, CT, MRI) are essential

3. Fever Probable etiology should be taken into account –Fever in patient post surgery –Fever in patient with renal failure –Fever in patient with HIV positivity –Fever in patient with septicaemia –Fever of unknown origin Fever for 3 weeks with unknown origin despite 1 week intensive hospital evaluation –Fever in children –Fever in soft tissue inflammation –Fever in bone infection –Fever in patient with abdominal sepsis –Fever in patient with different tumors

4. Fever Radiopharmaceuticals –organ specific – show damage of appropriate organ (defect of functioning tissue) Tc-99m diphosphonates – bone scan Tc-99m DMSA - kidneys –organ non-specific – accumulates directly in inflammed tissue (little bit tumors, wounds, hematomas) Ga-67 citrate – infective, non-infective, tumors labeled leukocytes – pyogenic infection Tc-99m IgG – non-infective F-18 FDG

5. Ga-67 - properties Used in a form of citrate Binds to plasmatic proteins, excretion by kidneys (24 h) and then intestinal mucosa Degree of accumulation correlates with process activity Basic principles of accumulation: –Complexes with plasma transferrin –Binds to intracellular lactoferrin inside leukocytes –Can binds directly to some parts of bacteria Patient preparation: –Laxatives - fast elimination from the bowel

6. Ga-67 - procedure Injection of 150-180 MBq –high energy, long half-life, high absorbed dose, worse spatial resolution (image qual) Acquisition 4-6 h p.i., then from 24 h to 3-4 days Collimator for medium energy Whole-body study, spot view (larger frame matrix), SPECT

7. Ga-67 – clinical significance High sensitivity (90%) but low specificity – used as a locating agent – it locates site of damage so other more specific methods can be used More suitable for chronic inflammation Not very good for abdominal inflammation evaluation due to physiological excretion via intestinal mucosa

8. Ga-67 – clinical indications Specific inflammation (sarcoidosis, tuberculosis) Imunocompromised patients (lung inf) Thoracic inflammation (fibrosis, vasculitis) Non-infective inflam – process activity (kollagenosis) Fever of unknown origin –wide spectrum of possible causes Osteomyelitis Abdominal and retroperitoneal inflamation (pyelonefritis, absces)

9. Labeled leucocytes properties Basic pinciples of accumulation –positive chemotaxis (no injury during labeling process) –also healing wounds and tumors Labeling process –in vitro - separation, laboured –in vivo - monoclonal antibodies Patient preparation –fasted (blood processing)

10. Labeled leucocytes procedure Labeling –60 ml venous blood (kids min. 12 ml) –separation, washing up, labeling – cca 1.5 h –Labeling with Tc-99m HMPAO (300 – 500 MBq) or In-111 oxin (20-40 MBq) Data acquisition –30 min, 4-6, 24 (48 In) h post injection –Whole-body study, spot view (larger frame matrix), SPECT

11. Labeled leucocytes clinical indication Unspecific bowel disease (Crohn, UC) Diabetic foot syndroma Musculosceletal infection Fever of unknown origin (within 2-3 w) Imunocompromised patients Joint prosthesis infection Acute arthritis Vascular prosthesis infection

12. Tc-99m IgG Non-specific polyclonal Labeled with In-111 or Tc-99m. Accumulates predominantly within interstitial space Physiological accumulation – blood-pool, liver, spleen, kindeys, bone marrow and nasal mucosa Main indication –Revmatic (non-infective) inflamation

13. F-18 FDG Metabolic analog of glucose –enter cells but no metabolism – accumulates according to degree of metabolic turnover Imaging by PET Metabolically active processes (inflam, tumors) - more glucose than other tissue Mainly used as a locating agent (like Ga- 67) and mark of activity PET – much better spatial resolution (better image quality)

14. New ways Imaging of bacteria –labeled chemotherapeuticals (chinolony) dependent on antibiotics therapy Chemotactic peptides –interleukin 2 – non-infective inflammation (autoimmune) Combined methods –Streptavidin (tissue senzibilization) and then labeled biotin

15. Ga-67 citrate physiological distribution male and female

16. Ga-67 - sarkoidosis

17. Ga-67 – sarkoidosis panda-sign

18. Ga-67 – sarkoidosis panda and delta sign

19. Ga-67 – lung fibrosis

20. Ga-67 - tuberculosis

21. Ga-67 - urosepticaemia

22. Ga-67 – thyroiditis comparison with Tc-99m pertechnetate

23. Labeled leucocytes physiological distribution

24. Labeled leucocytes ulcerative colitis

25. Labeled leucocytes ulcerative colitis or Crohn´s disease?

26. Labeled leucocytes ulcerative colitis

27. Labeled leucocytes infection of hip prosthesis

28. Diabetic foot syndroma

29. Patient JU 1961, X-ray chron. OM

30. Patient JU 1961, bone scan posit.

31. Patient JU 1961, leu scan negative

32. F-18 FDG physiological distribution

33. FUO Fever of unknown origin (all methods failed) PET revealed: - aortitis/vasculitis As a bonus: - Breast cancer (vasculitis as a paraneoplastic sign)

34. Vascular prosthesis infection PET FDG

35. Joint prosthesis infection PET FDG