NUCLEAR MEDICINE SCINTIGRAPHY

OF
INFLAMMATION 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 Medicine

Radiological

Information

Pathophysiology
Pathobiochemical

Morphological
change

Image

Whole body

Localize

Procedure

Time consumptive

Quick

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

Radiopharm.

Physical
characteristic
T1/2
(h)

Ga-67 citrate

78

Uptake mechanism

Energy
(KeV)
93, 185, Binding to transferrin, lactoferrin
300, 294 in activated leucocytes and
bacterial siderophorus.
Leakage through vessels with
increased permeability

Clinical indications:
Normal Biodistribution: hepar, skeletal,
colon, nasopharyngeal.
Acquisition: 18-72 h after injection

FUO,
Chronic osteomielitis of spine,
Lung infections,
Autoimmune disorders,
Neoplasm

Radiopharm.

In-111/
Tc-99m leucocytes

Physical character
T1/2
(h)

Energy
(KeV)

67
6

173, 247
140

Uptake mechanism

Chemotaxis

Preparation: Separate the leucocytes from erythrocytes and platelets.

The majority leucocytes labeled are neutrophils.

Normal distribution:
111
In-labeled leukocyte:
Liver, spleen, and bone marrow.
Acquisition: 24 h after injection

Tc-HMPAOlabeled leukocyte:
Liver, spleen , bone marrow, Colon, UT

99m

1 h, 4 h and 24 hr

Clinical Indications
In-111 leucocytes
Chronic osteomielitis
IBD
Renal infections
FUO
Bronchiectasi

Tc-99m HMPAO leucocytes

Acute osteomielitis
IBD
Vascular prothesis
Soft tissue infections

Radiopharm.

In-111/
Tc-99m HIG

Physical character
T1/2
(h)

Energy
(KeV)

67
6

173, 247
140

Uptake mechanism

Non-specific via increased

capillary permeability

Clinical indications: joints infection and inflammation

F-18 FDG

1.8

Clinical indications: (?) FUO

511

Upregulated 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%.

Radiopharm.

Tc-99m MDP

Physical character
T1/2
(h)

Energy
(KeV)

140

Uptake mechanism

Depends on blood flow and the

rate of new bone formation
(osteoblastic cells)

Osteomielitis study 3 phase:

1. The flow or perfusion
focal hyperperfusion
2. The blood pool or soft tissue
focal hyperemia
3. The bone (2-4 h pi image)
focally increased bony uptake
Fourth phase, next-day imaging:
improves the specificity.

New trend:
Leucocytes migration Large receptor specific proteins
Receptor specifik small proteins and peptide
All radiopharmaceutical for imaging inflammation
Can not distinguish between sterile inflammation from
infection process

Radiopharm.

Tc-99m quinolone

Physical character
T1/2
(h)

Energy
(KeV)

140

Uptake mechanism

Active bacterial DNA gyrase

Clinical indications:
Bone and joint infection
Fit fall: dormant bacteria
Criteria:
(+)ve uptake 4h > 1h
(-)ve uptake 4h < 1h
Acquisition: 1h and 4h

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.

Radiopharm.

Tc-99m ethambutol

Physical character
T1/2
(h)

Energy
(KeV)

140

Uptake mechanism

Direct bound to
mycobacterium Tbc

Case with prolong fever and

lymphadenopathy coli sinistra
PA (node FNAB) confirm for
specific infectious

 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)

1. Illness of at least 3-wk duration,
2. 1 week of in-hospital investigation,
3. 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

Diagnostic flow chart for FUO

Clinical examination
Blood, feces and urine test (ESR, CRP, CEA, etc) or Bone scan (Tc-99m MDP)
Higher probability for neoplasm
Ga-67 scan
+

No defined hypothesis

Higher prob for infection

Ga-67 scan

WBC/HIG/antibiotic scan
+

PET
+

Clinical
reevaluation

Clinical
follow-up

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.

(A)Uptake is greater on the Ga-67 image than on the bone image

positive osteomyelitis.
(B)Periprosthetic activity on the bone image but the Ga-67 normal
negative infection.
(C)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.

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