NUCLEAR MEDICINE SCINTIGRAPHY OFINFLAMMATION AND INFECTION

Dept. of Nuclear Medicine School of Medicine Universitas Padjadjaran

Inflammation: Is a non-specific, defensive response of the body to tissue damage. Has 3 basic stages: 1. Vasodilatation and increased permeability of blood vessels. 2. Emigration of phagocytes from the blood into interstitial fluid 3. Tissue repair. The signs & symptoms: redness, swelling, heat, pain, loss of function.

Vasodilation more blood to follow through the damaged area.

Increased permeability defensive proteins (antibodies, clothing factors) enter to the injured area. helps remove microbial toxins and dead cells.

Emigration of leucocytes

Chemotaxis Neutrophil cells enter to tissue phagocyte the microbes Monocyte cells (late phase) become macrophages

Acute inflammation: hyperemia, increased vascular permeability with exudation of protein, leucocytes migration.

Chronic inflammation: dominant: macrophages, lymphocytes & plasma cells, hyperemia and vascular permeability are less severe.

Infection simply means contamination with micro-organism.

The inflammation can due to infection or non-infection process: neoplasm, trauma, ischemia, etc.

Infection without inflammation: in severely immunocompromised patient.

Critical step in infectious and inflammatory processes: Early diagnosis Determine the foci NM and/or Radiological

Nuclear MedicineRadiologicalInformationPathophysiologyPathobiochemicalMorphological changeImageWhole bodyLocalizeProcedureTime consumptiveQuick

Radiopharmaceutical for inflammation and infection

1. Ga-67 citrate

2. In-111 or Tc-99m labeled leucocytes

3. In-111 or Tc-99m HIG

4. Tc-99m MDP

Normal Biodistribution: hepar, skeletal, colon, nasopharyngeal.

Acquisition: 18-72 h after injectionClinical indications: FUO, Chronic osteomielitis of spine, Lung infections, Autoimmune disorders, Neoplasm

Radiopharm.Physical characteristicUptake mechanismT1/2 (h)Energy (KeV)Ga-67 citrate7893, 185, 300, 294Binding to transferrin, lactoferrin in activated leucocytes and bacterial siderophorus.

Leakage through vessels with increased permeability

Normal distribution:111In-labeled leukocyte: 99mTc-HMPAOlabeled leukocyte: Liver, spleen, and bone marrow. Liver, spleen , bone marrow, Colon, UT

Acquisition: 24 h after injection 1 h, 4 h and 24 hrPreparation: Separate the leucocytes from erythrocytes and platelets. The majority leucocytes labeled are neutrophils.

Radiopharm.Physical characterUptake mechanismT1/2 (h)Energy (KeV)In-111/Tc-99m leucocytes67 6173, 247 140 Chemotaxis

Clinical IndicationsIn-111 leucocytesChronic osteomielitisIBDRenal infectionsFUOBronchiectasiTc-99m HMPAO leucocytesAcute osteomielitisIBDVascular prothesisSoft tissue infections

Clinical indications: joints infection and inflammationClinical indications: (?) FUO

Radiopharm.Physical characterUptake mechanismT1/2 (h)Energy (KeV)In-111/Tc-99m HIG67 6173, 247 140Non-specific via increased capillary permeability

F-18 FDG1.8511Upregulated GLUT-1 in activated granulocytes, lymphocytes, monocytes

FDG (F-18 Deoxyglucose)Fluorine-18 fluorodeoxyglucose (FDG) adalah suatu emiter positron dan istimewanya ditangkap oleh sel terutama yang mengalami metabolisme glukosa sebagai sumber energi seperti pada cancer and inflamation cel (netrofil and macropage).

Ketika dirangsang, sel-sel radang mengeluarkan transporter glukosa dengan konsentrasi tinggi (GLUT-1 to GLUT-7) yang memfasilitasi pemasukan FDG kedalam sel.

Tetapi pada studi prospektif menunjukkan lebih bagus dibanding Ga-67 pada pencitraan FUO, dengan sensitifitas dan spesifisitas 81% dan 86%.

Osteomielitis study 3 phase:

The flow or perfusion focal hyperperfusion

The blood pool or soft tissue focal hyperemia

The bone (2-4 h pi image) focally increased bony uptake

Fourth phase, next-day imaging:improves the specificity.

Radiopharm.Physical characterUptake mechanismT1/2 (h)Energy (KeV)Tc-99m MDP6140Depends on blood flow and the rate of new bone formation (osteoblastic cells)

New trend:Leucocytes migration Large receptor specific proteins Receptor specifik small proteins and peptide

All radiopharmaceutical for imaging inflammationCan not distinguish between sterile inflammation from infection process

Clinical indications:Bone and joint infectionFit fall: dormant bacteriaCriteria:(+)ve uptake 4h > 1h(-)ve uptake 4h < 1h

Acquisition: 1h and 4h

Radiopharm.Physical characterUptake mechanismT1/2 (h)Energy (KeV)Tc-99m quinolone6140Active bacterial DNA gyrase

Tc-99m Ciprofoxacin (Infecton)Ciprofoxacin quinolon antibiotik berspektrum luas DNA bakteri.

In-vitro ditangkap bakteri gram positif, negatif dan anaerob.

Hall dkk (1997) suatu studi komparatif : spesifisitas tinggi (96%).

Infeksi resisten juga bisa dicitra dan tidak berefek oleh terapi antibiotik sebelumnya.

sensitivitas 85% dan spesifisitas 82%Sensitivitas 90% pada osteomyelitis dan spesifisitas 90% pada infeksi luka bedah.Monitor respon terapi antibiotik kapan dihentikan.

Case with prolong fever and lymphadenopathy coli sinistraPA (node FNAB) confirm for specific infectious

Radiopharm.Physical characterUptake mechanismT1/2 (h)Energy (KeV)Tc-99m ethambutol6140Direct bound to mycobacterium Tbc

Figure-Schematic diagram of the approach to imfection imaging Broad spectrum agent for imaging infection, inflmation and tumors (e.g. HIG, FDG)

Inflammation specific agent (e.g. radiolabelled leucocytes and endogenous antimicrobial peptides)

Infection specific agent

Bacteria Fungi Viruses/Parasites

- Gram+ves, Gram-ves, anaerobes -Yeasts (e.g Tc-99m (e.g Tc-99m ciprofloxacin) fluconazole) - Mycobacteria(e.g Tc-99m ethambutol) -Aspergillus - Atypicals (e.g Mycoplasma, -Other fungi Chlamydia)

FUO (Fever Unknown Origin)Illness of at least 3-wk duration, 1 week of in-hospital investigation,No clue as to the cause of fever.

Causa:Infection 20-30%Neoplasms 15-25%Other, including drug induced fever

Study (no correct approach)Ga-67 first Up to 20% caused by tumor Many disease having monocytic &/ lymphocytes infiltrate

Labeled leucocytes first Appropriate energy and T1/2 Activity doses < Ga-67

FDG first Can pick up much pathology that can cause fever

Labeled antibiotic first For patients who came from high prevalence of infectious disease area or high probability for infection

Clinical examinationBlood, feces and urine test (ESR, CRP, CEA, etc) or Bone scan (Tc-99m MDP)No defined hypothesisHigher prob for infectionHigher probability for neoplasmGa-67 scanWBC/HIG/antibiotic scanGa-67 scan-+-+-+PET-+Clinical reevaluationClinical follow-upDiagnostic flow chart for FUO

Ga-67 image is intense, diffuse pulmonary activity, typical of Pneumocystis carinii pneumonia. The labeled leukocyte study, shows normal findings. for detecting most opportunistic infections. Post surgeries with a mass on a CT scan of the abdomen and pelvis (arrow). DD/. postoperative changes and tumor, but not infection.

Abnormal accumulation of labeled leukocytes extends through the left abdomen into the thigh (arrowheads). Multiple abscesses were subsequently drained.

Uptake is greater on the Ga-67 image than on the bone image positive osteomyelitis. Periprosthetic activity on the bone image but the Ga-67 normal negative infection. Distributionf both tracers around a left hip prosthesis are similar equivocal for infection.

Croasdale J dkk ( WJNM 2005) - FUO radiopharmaceutical : Tc-99m HMPAO, Ga-67, FDG dan Tc-99m/In-111 HIG.

- Ga-67 (choice agent) FUO and infection >2 weeks.

- Ga-67 tidak untuk diagnosa tapi melokalisasi infeksi dilanjutkan dengan modalitas lain. - uptake Ga-67 meningkat pada infeksi dan inflamasi. - In-111/Tc-99m dilabel leukosit sering digunakan untuk melokalisasi infeksi.

Corstens dkk (1999) : radiofarmaka untuk infeksi jairngan lunak Tc-99m leukosit dan Ga-67 sedang untuk FUO In-111 leukosit dan Ga-67.

Buscombe J (1998). - Early detection of PID ultrasound; but operator dependent. - spiral CT slicing 1-2 cm pada abses kecil juga sulit. - dibanding Ga-67 dan Tc-99m HMPAO leukosit maka In-111 leukosit lebih sering dipakai dan disukai untuk diagnosa infeksi intra pelvic.

Terima Kasih